tbuckley/cabot-search huggingface dataset:
EPCO-06. AGE- AND REGION-SPECIFIC MULTI-OMIC CHARACTERIZATION OF H3-K27M MUTANT DIFFUSE MIDLINE GLIOMA
Authors: Ilon Liu, Jiang Li, Daeun Jeong, Olivia A Hack, McKenzie Shaw, Bernhard Englinger, Byron Avihai, Kati Ernst, Adam Resnick, Aaron Diaz, David Jones, Carl Koschmann, Claudia Kleinman, Nada Jabado, Jennifer Cotter, Keith Ligon, Sanda Alexandrescu, W K Alfred Yung, Thomas Czech, Isabel Arrillaga-Romany, Johannes Gojo, Irene Slavc, Michelle Monje, Mariella G Filbin
Journal: Neuro-Oncology (2021)

Abstract Diffuse midline gliomas driven by lysine27-to-methionine mutations in histone 3 (H3-K27M DMGs) are among the most fatal brain tumors. Molecular studies including single cell RNA-sequencing (scRNA-seq) of pediatric and predominantly pontine H3-K27M DMGs have shown that the H3-K27M oncohistone keeps glioma cells locked in a stem-like oligodendrocyte precursor cell (OPC) state that is capable of self-renewal and tumor-initiation. However, a comprehensive dissection of the cellular architecture of H3-K27M DMGs across different midline regions and age groups is required to better understand the cell-intrinsic and contextual regulation of H3-K27M DMG cell identities. In particular, the more recently described group of adult H3-K27M DMGs remains understudied. Here, we have collected and characterized 45 H3-K27M mutant patient tumors, spanning pontine (n=26), thalamic (n=17), and spinal (n=2) locations. Median age at surgery was 12 (2-68) years, encompassing 21 early childhood (0-10 years), 12 adolescent (11-20 years), and 12 adult (≥ 21 years) tumors. The majority of samples were obtained pre-treatment (n=28), as opposed to post-treatment or at autopsy (n=17). We profiled all 45 tumors by single cell/single nucleus RNA-seq and selected tumors were further characterized by the single cell assay for transposase-accessible chromatin (scATAC-seq). Our integrated analyses highlight the predominance of transcriptionally and epigenetically defined OPC-like tumor cells as the main cell population of H3-K27M DMGs across all age groups and locations. We further identify distinct age- and location-specific OPC-like cell subpopulations. Comparison of pediatric and adult tumors further demonstrates a significant increase of mesenchymal cell states in adult H3-K27M DMGs, which we link to differences in glioma-associated immune cell compartments between age groups. Together, this study sheds light on the effects of age- and region-dependent microenvironments in shaping cellular identities in H3-K27M DMGs.
Treating Severe Hypercholesterolemia—If Not Now, When?
Authors: Neil J. Stone
Journal: JAMA Cardiology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Developing a Safer Anti-CD44v6 Chimeric Antigen Receptor T Cell Against Hematological Cancers By Mitigating on-Target Off-Tumor Toxicity
Authors: Dennis Awuah, Lawrence Stern, Ian Schrack, Tae Yoon Kim, Joseph Cohen, Ryan Urak, Christian Huynh, Wen-Chung Chang, Stephen J Forman, Xiuli Wang
Journal: Blood (2021)
Abstract 9018: Risk of Ventricular Arrhythmias Following Implantable Cardioverter-Defibrillator Generator Change in Patients With Recovered Ejection Fraction: Implications for Decision-Making
Authors: Donald D Chang, Peter Pantlin, Francis Benn, Cody M Williams, Michael L Bernard, Aimee E Hiltbold, Sammy Khatib, Glenn M Polin, Paul A Rogers, Daniel P Morin
Journal: Circulation (2021)

Introduction: Guidelines indicate primary-prevention ICDs for most patients with LVEF ≤35%. Some patients’ EFs improve to &gt;35% during the life of their first ICD. In present practice, ICDs most often are replaced regardless of EF. In patients with recovered EF&gt;35% who have never received appropriate ICD therapy, the utility of ICD generator replacement remains unclear. We evaluated the risk of ventricular arrhythmias in relation to EF at the time of ICD generator change in patients with no history of appropriate tachycardia therapy from their original ICD. Methods: We enrolled patients with a primary-prevention ICD originally implanted for systolic cardiomyopathy with EF ≤35%, who underwent ICD generator change within our multihospital health system. Patients who required appropriate ICD therapy for VT/VF prior to generator change were excluded. Results: Among 539 generator changes, 291 patients (69±12 y, 63% men, 29% Black, EF 34±15%) met inclusion criteria. During follow-up of 3.9±2.3 years, 62 (21%) received appropriate therapy for VT/VF. Compared to patients with recovered EF &gt;35% (n=109 [37%]), those with EF persistently ≤35% (n=182 [63%]) were more likely to require subsequent ICD therapy (12% vs. 27%, p=0.003). ROC analysis among those with EF &gt;35% revealed the optimal cutoff for VT/VF prediction to be EF 45% (AUC 0.71, p=0.01). Kaplan-Meier analysis demonstrated considerably higher VT/VF-free survival among those with LVEF ≥45% vs. &lt;45% (Figure; p&lt;0.001); estimated 5-year event rates: 6% vs. 35%. On multivariable analysis, EF was independently predictive of VT/VF (adjusted HR per 1% EF increase: 0.90 [0.81-0.99]; p=0.04). Conclusion: At the time of ICD generator change, patients with primary-prevention ICDs and EF ≥45% with no prior ICD therapy have a significantly lower rate of subsequent ventricular arrhythmias compared to those with EF &lt;45%. These data may be useful during shared decision-making at the time of ICD generator battery depletion.
Phase II Trial of Response Adapted Ultra Low Dose (ULD) Orbital Radiation Therapy for Indolent B Cell Lymphoma
Authors: Chelsea C. Pinnix, Bouthaina S. Dabaja, Jillian R. Gunther, Penny Fang, Susan Wu, Loretta Nastoupil, Paolo Strati, Ranjit Nair, Sairah Ahmed, Raphael E Steiner, Luis Malpica-Castillo, Dai Chihara, Preetesh Jain, Luis Fayad, Jason R. Westin, Sattva S. Neelapu, Maria Alma Rodriguez, Fredrick B. Hagemeister, Hun Ju Lee, Michael Wang, Felipe Samaniego, Nathan H. Fowler, Christopher R. Flowers, Lei Feng, Linda Chi, Bita Esmaeli
Journal: Blood (2021)
The Clonotypic BCR IG of CLL Patients Contain Predicted T-Cell Class I Epitopes with Shared Structural Properties
Authors: Anna Vardi, Andreas Agathangelidis, Sofia Gkagkaridou, Anna-Lisa Schaap-Johansen, Maria Karipidou, Anna Boukla, Asimina Fylaktou, Niki Stavroyianni, Michail Iskas, Achilles Anagnostopoulos, Sine Reker Hadrup, Anastasia Chatzidimitriou, Paolo Marcatili, Kostas Stamatopoulos
Journal: Blood (2021)
Abstract 13779: Microvascular Endothelial Function, Long-Term Dietary Intervention and Cardiovascular Risk of Recurrence: From the CORDIOPREV Study
Authors: Marta Millan-Orge, Jose D torres-Peña, Antonio P Arenas-Larriva, Gracia M Quintana-Navarro, Patricia Peña-Orihuela, Juan F Alcala-Diaz, NIKIK KATSIKI, Jose Lopez-Miranda, Pablo Perez-Martinez, Francisco Javier Delgado Lista
Journal: Circulation (2021)

Introduction: Microvascular circulation controls tissue perfusion. Its dysfunction is implicated in damage to the myocardium and is a predictor of cardiovascular events. It has been shown that short-term dietary interventions may influence microvascular endothelial function (MEF) in some populations. There is a lack of evidence on the long-term effect of healthy diet patterns on MEF in patients with coronary heart disease (CHD) and on whether this effect is modified by the risk of CHD recurrence. Hypothesis: the consumption of healthy diets (Mediterranean diet or Low-fat diet) improves the MEF of CHD patients in the long term, and this effect is interrelated with the risk of CHD recurrence. Methods: In the CORDIOPREV study, dietary intervention with a Mediterranean diet or a low-fat diet is being carried out in 1002 patients with CHD for 7 years. The effect of this dietary intervention on basal microvascular flow and the area of hyperemia reactive to hypoxia was evaluated in 664 patients by laser-Doppler flowmetry at baseline and after 6 years of intervention. The risk of recurrence of CHD in patients was evaluated according to the TRS2P risk score. Results: Basal flow and reactive hyperemia area improved after the dietary intervention in the population (basal flow 97.78 ± 2.79 vs. 179.31 ± 5.06 arbitrary perfusion units, 83.38% increase, p&lt;0.001) (reactive hyperemia 4233.3 ± 127.73 vs. 9695.9 ± 205.23 arbitrary perfusion units per time, 129.04% increase, p&lt;0.001), without finding differences due to the diet (p&gt;0.05 for the diet-effect). When patients were stratified to low, medium or high risk of recurrence, the basal flow was similarly increased in all three groups, but the reactive hyperemia area was improved to a greater extent in patients in the low-risk group compared with those in the medium or high risk groups. Conclusion: Long-term consumption of a healthy dietary pattern improves MEF in patients with CHD, and this improvement is greater in patients in the low-risk category for cardiovascular recurrence compared with those in the medium and high-risk groups.
Real-World Efficacy and Safety Outcomes for Patients with Relapsed or Refractory (R/R) Aggressive B-Cell Non-Hodgkin's Lymphoma (aBNHL) Treated with Commercial Tisagenlecleucel: Update from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry
Authors: Daniel J Landsburg, Matthew J. Frigault, Zhen-Huan Hu, Samantha Jaglowski, Frederick L. Locke, Christine Ho, Miguel-Angel Perales, Caron Jacobson, Brian T. Hill, Stephen Ronan Foley, Peter A. Riedell, Ranjan Tiwari, Aisha Masood, Stephen Lim, Marta Majdan, Marcelo C Pasquini, Cameron J. Turtle
Journal: Blood (2021)
Durability of Platelet Response When Switching from Eltrombopag or Romiplostim to Avatrombopag in Immune Thrombocytopenia (ITP): A Multicenter Study
Authors: Hanny Al-Samkari, Debbie Jiang, Terry B. Gernsheimer, Howard A. Liebman, Susie Lee, Chelsea Bernheisel, Scott Kolodny, Matthew Wojdyla, Michael Vredenburg, Brian Jamieson, Adam Cuker
Journal: Blood (2021)
Event-Free and Overall Survival in over 6,000 Patients Treated with Frontline Immunochemotherapy for Follicular Lymphoma between 2002-2018: First Report from the International FLIPI24 Consortium
Authors: Matthew J. Maurer, Vit K Prochazka, Christopher R. Flowers, Lasse H. Jakobsen, Diego Villa, Caroline Weibull, Elliot J. Cahn, Herve Ghesquieres, Robert Kridel, Maher Gandhi, Chan Yoon Cheah, Eliza Hawkes, John F. Seymour, Ciara L. Freeman, Michael Roost Clausen, Björn Wahlin, Brian K. Link, Karin Ekstroem Smedby, Laurie H. Sehn, Marek Trněný, Tarec Christoffer El-Galaly, James R. Cerhan
Journal: Blood (2021)
<i>Dnmt3a</i> Inactivation Leads to Slow DNA Methylation Loss in Murine Hematopoietic Cells <i>In Vivo</i>
Authors: Amanda M Smith, Angela Maria Verdoni, Shamika Ketkar, Elizabeth Leight, David Y Chen, Sai Mukund Ramakrishnan, Christopher A Miller, Haley J Abel, Timothy J Ley
Journal: Blood (2021)
High Frequency of CNS Involvement in Transformed Waldenström Macroglobulinemia
Authors: Eric Durot, Lukshe Kanagaratnam, Saurabh Zanwar, Elise Toussaint, Efstathios Kastritis, Shirley D'Sa, Miguel Alcoceba, Cécile Tomowiak, Bénédicte Hivert, Caroline Protin, Jithma P. Abeykoon, Josephine M.I. Vos, Anne-Sophie Michallet, Cyrielle Rodier, Jehan Dupuis, Stéphane Leprêtre, Fatiha Merabet, Xavier Roussel, Jean-Marc Zini, Caroline Regny, Aisha S Patel, Pierre Morel, Damien Roos-Weil, Steven P. Treon, Meletios A. Dimopoulos, Ramon Garcia-Sanz, Prashant Kapoor, Jorge J. Castillo, Alain Delmer
Journal: Blood (2021)
Blinatumomab Is Cost-Effective Compared to Standard Chemotherapy for Children with High Risk Relapses of Acute Lymphoblastic Leukemia: A Cost-Effectiveness Analysis Using Population-Based Healthcare Data
Authors: Petros Pechlivanoglou, Linda Luu, Qing Li, Paul J. Gibson, Uma H. Athale, Mylene Bassal, Vicky R. Breakey, Serina Patel, Jason Pole, Rinku Sutradhar, Laura Wheaton, Nicole Mittmann, Sumit Gupta
Journal: Blood (2021)
Dual Inhibition of the MEK/ERK and PI3K/AKT Pathways Prevents Pulmonary Graft-Versus-Host Disease through Suppression of Arteriovenous Inflammation and Bronchiolitis
Authors: Hiroyuki Muranushi, Takero Shindo, Huong Thi Ngo, Fumiaki Gochi, Akihiko Yoshizawa, Toyofumi Fengshi Chen-Yoshikawa, Akifumi Takaori-Kondo
Journal: Blood (2021)
Predictors for Improvement in Patient-Reported Outcomes: <i>Post-Hoc</i> Analysis of a Phase 3 Randomized, Open-Label Study of Eculizumab and Ravulizumab in Complement Inhibitor-Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)
Authors: Hubert Schrezenmeier, Austin G. Kulasekararaj, Lindsay Mitchell, Regis Peffault De Latour, Timothy Devos, Shinichiro Okamoto, Richard Wells, Karissa Johnston, Evan Popoff, Antoinette Cheung, Jimmy Wang, Philippe Gustovic, Alice Wang, Ioannis Tomazos, Yogesh Patel, Jong Wook Lee
Journal: Blood (2021)
Trial in Progress: Phase 1/2 Study Evaluating the Safety and Efficacy of Iov-2001, an Autologous, Non-Genetically Modified, Polyclonal T-Cell Product, in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
Authors: Javier Pinilla Ibarz, Meixiao Long, John Lister, Jennifer A. Woyach, Friedrich Graf Finckenstein, Madan Jagasia, Selda Samakoglu, Bhagyashree Yadav, Huiling Li, John C. Byrd
Journal: Blood (2021)
Leukemic Stem Cells of Monocytic AMLs Are Not-Resistant to BCL-2 Inhibition
Authors: Simon Renders, Aino-Maija Leppä, Alexander Waclawiczek, Maike Janssen, Elisa Donato, Cecilia Reyneri, Julia M. Unglaub, Michael Hundemer, Richard F. Schlenk, Simon Raffel, Carsten Müller-Tidow, Tim Sauer, Andreas Trumpp
Journal: Blood (2021)
Efficacy of Vecabrutinib Treatment in a Murine Model of Sclerodermatous Graft-Versus-Host-Disease
Authors: Kamira Maharaj, Melanie Mediavilla-Varela, Angimar Uriepero, Judith A. Fox, Pietro Taverna, Wael Gamal, Eva Sahakian, Javier Pinilla Ibarz
Journal: Blood (2021)
Safety and Efficacy of Menin Inhibition in Patients (Pts) with MLL-Rearranged and NPM1 Mutant Acute Leukemia: A Phase (Ph) 1, First-in-Human Study of SNDX-5613 (AUGMENT 101)
Authors: Eytan M. Stein, Ibrahim Aldoss, John F. DiPersio, Richard M. Stone, Martha L. Arellano, Galit Rosen, Michael L. Meyers, Yifan Huang, Steve Smith, Rebecca G. Bagley, Michael Thirman, Manish R. Patel, Ghayas C. Issa
Journal: Blood (2021)
Post Transplantation Fludarabine and Cyclophosphamide Selected and Promoted Low Dose of Unrelated UCB Implanation in Combined Transplantation of Haploid and UCB Stem Cells in Childhood Leukemia: 40 Cases Report in Double Center
Authors: Yuhua Xiao, Sixi Liu, Chunfu Li, Wing Hang Leung, Xiaoqin Feng, Yuelin He, Xiaodong Wang, Xiaoling Wang, Li Yu, Libai Chen, Jianyun Wen, Xuan Liu, Yongsheng Ruan, Xiaoting Liu, Yuqiong Ren
Journal: Blood (2021)
Targeting PRAME with TCR-Mimic CAR T Cells in AML
Authors: Anisha M Loeb, Sommer Castro, Cynthia Nourigat-Mckay, LaKeisha Perkins, Laura Pardo, Amanda R. Leonti, Thao T. Tang, Lindsey F Call, Tiffany A. Hylkema, David A. Scheinberg, Soheil Meshinchi, Quy Le
Journal: Blood (2021)
Mental Stress–Induced Myocardial Ischemia
Authors: Paco E. Bravo, Thomas P. Cappola
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Case of Extrinsic Compression of the Left Main Coronary Artery by Dilated Pulmonary Artery in Eisenmengers Syndrome
Authors: Varshit Hathi, Nagamani Alur Chikkabasavaiah, Beeresh Puttegowda, Yeriswamy Yeriswamy, Ramesh Basavappa, Manjunath Cholenally Nanjappa
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

The extrinsic compression of the left main coronary artery secondary to pulmonary artery trunk dilatation is a relatively rare syndrome. [1,2] It is mostly associated with congenital acyanotic heart disease, idiopathic pulmonary arterial dilatation or primary pulmonary hypertension. [3,4] Most cases of pulmonary artery hypertension with no atherosclerotic risk factors rarely undergo coronary angiography, and hence, diagnoses are seldom made and proper management is delayed.We describe a patient with Ostium secundum atrial septal defect with severe pulmonary hypertension who presented with clinical angina ,diagnosed to have left main coronary artery compression by CT angiography ,underwent successful percutaneous coronary intervention with good symptomatic relief.
The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis
Authors: Nipat Chuleerarux, Saman Nematollahi, Achitpol Thongkam, M. Veronica Dioverti, Kasama Manothummetha, Pattama Torvorapanit, Nattapong Langsiri, Navaporn Worasilchai, Rongpong Plongla, Ariya Chindamporn, Anawin Sanguankeo, Nitipong Permpalung
Journal: Clinical Microbiology and Infection (2021)
Real-Life CAR-T Cell Treatment in Large B-Cell Lymphomas Indicates That Axi-Cel and Tisa-Cel Have Similar Outcomes, but Long-Term Cytopenia Is an Emerging Problem
Authors: Annalisa Chiappella, Anna Guidetti, Anna Dodero, Stefania Bramanti, Pier Luigi Zinzani, Armando Santoro, Beatrice Casadei, Alice Di Rocco, Matteo Giovanni Carrabba, Patrizia Chiusolo, Massimo Martino, Anna Maria Barbui, Maria Chiara Tisi, Riccardo Saccardi, Vincenzo Maria Perriello, Enrico Orciuolo, Barbara Botto, Domenico Russo, Rosalba Miceli, Silva Ljevar, Cristiana Carniti, Paolo Corradini
Journal: Blood (2021)
Impact of drug treatment and drug interactions in post-stroke epilepsy
Authors: Lanqing Zhao, Jinwei Li, Reetta Kälviäinen, Jukka Jolkkonen, Chuansheng Zhao
Journal: Pharmacology & Therapeutics (2021)

Stroke is a huge burden on our society and this is expected to grow in the future due to the aging population and the associated co-morbidities. The improvement of acute stroke care has increased the survival rate of stroke patients, and many patients are left with permanent disability, which makes stroke the main cause of adult disability. Unfortunately, many patients face other severe complications such as post-stroke seizures and epilepsy. Acute seizures (ASS) occur within 1 week after the stroke while later occurring unprovoked seizures are diagnosed as post-stroke epilepsy (PSE). Both are associated with a poor prognosis of a functional recovery. The underlying neurobiological mechanisms are complex and poorly understood. There are no universal guidelines on the management of PSE. There is increasing evidence for several risk factors for ASS/PSE, however, the impacts of recanalization, drugs used for secondary prevention of stroke, treatment of stroke co-morbidities and antiseizure medication are currently poorly understood. This review focuses on the common medications that stroke patients are prescribed and potential drug interactions possibly complicating the management of ASS/PSE.
Clinical Characteristics and Outcomes of AML Patients Treated with Frontline CPX 351 or HMA/Venetoclax: A Single Institution's Experience
Authors: Aleksander L. Chojecki, Justin Arnall, Danielle Boselli, Kristyn Y. DiSogra, Allison Karabinos, Tommy Chen, Jing Ai, Thomas G. Knight, Brittany Knick Ragon, Nilay A. Shah, Srinivasa R. Sanikommu, James T Symanowski, Belinda R Avalos, Edward A. Copelan, Michael R. Grunwald
Journal: Blood (2021)
Abstract 9084: Selective Beta3-Adrenergic Receptor Antagonist Therapy Causes Regression of Cardiac Dysfunction in a Rat Model of Progressive Heart Failure: Insights into Molecular and Cellular Mechanisms
Authors: Xiaoqiang Sun, Che Ping Cheng, Jing Cao, Zhe Chen, Zhi Zhang, Tiankai Li, Xiaowei Zhang, David M Herrington, David Zhao, Heng Cheng
Journal: Circulation (2021)

Background: Heart failure (CHF) causes cardiac β 3 -adrenergic receptor (AR) upregulation with resultant enhanced β 3 -AR-stimulated-G i -coupled negative modulation on cardiac function. This suggests a direct and contributing role of β 3 -AR activation on CHF progression. However, its precise role is unclear. We hypothesize that up-regulation of cardiac β 3 -AR promotes CHF progression. Chronic β 3 -AR antagonist (ANT) may improve Left ventricular (LV) myocyte function, and β-adrenergic reserve, thus preventing the progression of CHF. Methods: LV and myocyte functional response and β 1 - and β 3 -AR expression were compared in 3 groups of SD male rats (8 each) during 3 months: 1) CHF, 3 months after receiving Isoproterenol (ISO, 170 mg/kg, sq, for 2 days); 2) CHF/β 3 -ANT, 2 months after receiving ISO, L-748,337, a selective β 3 -AR antagonist (β 3 -ANT) (10 -7 M/kg/day, mini pump) was initiated and was given for 1 month; and 3) sham controls. Results: Versus controls, ISO-treated rats had CHF onset at 1 month after ISO and progressed to severe CHF at 3 months. Plasma norepinephrine (NE, 1298 vs 261 pg/ml) increased 4-fold; whereas, stroke volume (SV) and ejection fraction (EF, 34 vs 62%) decreased more than 45%. These changes were parallel with significant reductions in cell contraction (dL/dt max , 95 vs 189 μm/s), relaxation (dR/dt max ,75 vs 158 μm/s) and [Ca 2+ ] i transient ([Ca 2+ ] iT ) (0.17 vs 0.26). Acute superfusion of ISO (10 -8 M) caused much less increases in dL/dt max (34 vs 74%), dR/dt max and [Ca 2+ ] IT (14 vs 28%). These changes were associated with significantly decreased β 1 -AR mRNA (52%, 0.30 vs 0.62), but increased β 3 -AR mRNA (119%, 1.25 vs 0.57) expression. CHF with β 3 -ANT treatment, significantly decreased plasma NE (197 pg/ml). EF (59%) and SV returned to normal control values. The signal ratios of β 1 -AR mRNA (0.59) and β 3 -AR mRNA (0.66) recovered to control levels. ISO-induced increases in dL/dt max (75%), dR/dt max and [Ca 2+ ] iT were also significantly augmented. Conclusion: Chronic β 3 -ANT leads to normalization of LV myocyte β 1 - and β 3 -AR gene expression, restores normal LV myocyte β-AR reserve, and leads to regression of LV and myocyte dysfunction in a rat model of progressive CHF. Thus, β 3 -AR blocker may provide a new therapeutic strategy for the treatment of CHF.