The federal Project Grant award of $100,050.00 from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) will support research to investigate the potential role of cardiometabolic drugs, such as glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2I), as well as the repurposing of metformin and bariatric surgery, in reducing the burden of atrial fibrillation (AF). The research...
This $810,964 Project Grant awarded by the National Heart, Lung, and Blood Institute (NHLBI), under the Cardiovascular Diseases Research (CFDA 93.837) program, supports the development of a novel non-invasive 3D mapping technique to accurately identify the site of origin for ventricular tachycardia (VT) and premature ventricular complexes (PVCs) using 12-lead ECG data. The project aims to create a computerized method that can automatically locate the VT exit/PVC origin site in real-time,...
This $200,000 Project Grant award from the National Science Foundation's Computer and Information Science and Engineering (CFDA 47.070) program will fund the development of advanced computational methods to create high-fidelity, fast-running digital twins of patient hearts and cardiovascular medical devices. The project aims to deliver: 1) novel machine learning algorithms for accurate digital twin geometry reconstruction from 3D medical images, 2) an efficient inverse method to identify in vivo...
This $997,770 project grant, awarded by the National Science Foundation (NSF) under the Mathematical and Physical Sciences (CFDA 47.049) program, aims to improve the accuracy and predictive capabilities of cardiac digital twin models for assessing the risk of sudden cardiac death. The research team at The Johns Hopkins University will develop novel, scalable, and data-driven mathematical and algorithmic calibration tools that combine advanced computational techniques and machine learning to...
This Project Grant award of $618,126 from the National Heart, Lung, and Blood Institute (CFDA 93.837 - Cardiovascular Diseases Research) supports research to elucidate the molecular mechanisms by which interleukin-6 (IL-6) signaling triggers proarrhythmic electrical changes and promotes lethal ventricular tachyarrhythmias (VT) in obesity-induced inflammation. The research aims to determine the anti-arrhythmic effects of inhibiting IL-6 trans-signaling and identify the underlying mechanisms of...
This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) will provide $171,450.00 to investigate the biological mechanisms linking excess body fat (adiposity) and elevated blood lipid levels, and their combined impact on cardiovascular disease risk. The research, led by Dr. Dron, a computational geneticist, aims to: 1) measure how adiposity interacts with genetic variants to influence lipid levels, 2)...
This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under CFDA 93.837 - Cardiovascular Diseases Research supports a research project to investigate the mechanisms by which obesity leads to atrial fibrillation. The $769,761 award to Weill Medical College of Cornell University aims to assess the roles of the NAD+ pathway and ATF6 ER stress pathway in obesity-induced atrial fibrillation, with the overall goal of gaining greater insight into the molecular pathogenesis...
The Regents of the University of California, San Francisco was awarded a $2.784 million Project Grant from the Department of Health and Human Services National Institutes of Health Office of the Director to develop AI-assisted imaging and prediction of cardiac arrhythmia origins using 4D ultrasound. The three-year grant, awarded under the Trans-NIH Research Support program, aims to generate an extensive dataset capturing the electrical and mechanical dynamics of arrhythmic hearts. An...
This $977,998.39 Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) will fund a clinical trial to evaluate the use of venous ethanol ablation (VE) in combination with radiofrequency (RF) catheter ablation for treating ischemic ventricular tachycardia (VT). The trial, titled "Venous Ethanol for Left Ventricular Ischemic Ventricular Tachycardia (VELVET)", will compare the efficacy and safety of...
This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) will fund research to generate human induced pluripotent stem cell (iPSC) models of type 2 diabetic cardiomyopathy (T2DCM) and assess the metabolic mechanisms and protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors. The total award is $511,864 with a project period from Sep 6, 2024 to Mar 31, 2026. The research will be...
HEART DIGITAL TWIN ANALYSIS OF ARRHYTHMIAS DUE TO INFILTRATING ADIPOSITY - PROJECT SUMMARY SUDDEN CARDIAC DEATH DUE TO VENTRICULAR ARRHYTHMIAS (VAS) IS A LEADING CAUSE OF MORTALITY WORLD-WIDE. DESPITE ADVANCEMENTS IN ANTI-ARRHYTHMIA THERAPIES, VA RATES REMAIN HIGH IN PART DUE TO AN INCOMPLETE UNDERSTANDING OF THE UNDERLYING DISEASE-INDUCED ARRHYTHMIGENIC SUBSTRATE. IN PATIENTS WITH PRIOR MYOCARDIAL INFARCTION, TRADITIONAL DOGMA HAS MAINTAINED THAT HETEROGENEOUS SCARRING IN THE VENTRICLES FORMS THE ARRHYTHMIA SUBSTRATE. WHILE CLINICAL STUDIES HAVE UTILIZED THE VISUALIZATION OF VENTRICULAR SCAR IN LOCALIZING VA ABLATION TARGETS, THESE EFFORTS HAVE FAILED TO SIGNIFICANTLY IMPROVE VA RECURRENCE RATES, SUGGESTING THAT SCAR CHARACTERIZATION ALONE MAY BE INSUFFICIENT FOR IDENTIFYING AND ELIMINATING VA. INFILTRATING ADIPOSE TISSUE (INFAT) IS A NEWLY RECOGNIZED ASPECT OF POST-INFARCT REMODELING. HOWEVER, BECAUSE INFAT IS INTERMINGLED WITH SCAR, THE SPECIFIC ROLE OF LNFAT IN VA PROPENSITY IN PATIENTS WITH ISCHEMIC CARDIOMYOPATHY HAS NEVER BEEN EXPLORED. THE OVERALL OBJECTLVE OF THIS APPLLCATLON IS TO USE A NOVEL COMBINATION OF MECHANISTIC PERSONALLZED COMPUTATLONAL MODELLNG ("DLGLTAL TWIN" OF THE HEART), IMAGING, ELECTROANATOMLCAL MAPPING, EX-VIVO HUMAN HEART EXPERIMENTS, AND ARTIFICIAL INTELLIGENCE (AL) TO COMPREHENSIVELY CHARACTERIZE THE ROLE OF INFAT VS. SCAR IN POST-INFARCT VAS, AND TO DEVELOP A NEW DIGITAL-TWIN APPROACH FOR GUIDANCE OF VA ABLATION IN PATIENTS WITH ISCHEMIC CARDIOMYOPATHY. LEVERAGING OUR ADVANCEMENTS IN THE ACQUISITION OF HIGH-QUALITY VENTRICULAR IMAGES OF SCAR AND INFAT DISTRIBUTION, OUR EXPERTISE IN PERSONALIZED COMPUTATIONAL MODELING AND AL, AND OUR CLINICAL AND EXPERIMENTAL EXPERTISE, WE PROPOSE TO DEVELOP PERSONALIZED HEART DIGITAL TWINS OF ICM PATINETS THAT INCORPORATE SCAR AND INFAT DISTRIBUTIONS AND ARE PARAMETERIZED WITH EXPERIMENTAL DATA. USING THE DIGITAL TWINS AND INTRA-PROCEDURE DATA, WE WILL EXPLORE THE MECHANISTIC ROLE OF INFAT IN ARRHYTHMOGENIC PROPENSITY AND IN THE COMPONENTS OF THE VA CIRCUIT. WE WILL ALSO UTILIZE THE DIGITAL TWINNING TECHNOLOGY TO DEVELOP A COMPREHENSIVE VA ABLATION GUIDANCE STRATEGY THAT ACCOUNTS FOR THE ROLES OF INFAT AND SCAR IN VA CIRCUITS. THE PROJECT WILL CULMINATE IN A CLINICAL TRANSLATION FEASIBILITY STUDY TO DEMONSTRATE THAT THE NOVEL DIGITAL TWINS OFFER ACCURATE PREDICTION OF VA ABLATION SITES, AND CAN BE USED FOR PRE-PROCEDURE GUIDANCE AND OPTIMAL TARGETING, ELIMINATING EXTENSIVE ELECTROANATOMICAL MAPPING. SUCCESSFUL EXECUTION OF THE PROPOSED STUDIES WILL PROVIDE NEW MECHANISTIC UNDERSTANDING OF THE ROLE OF INFAT IN PROMOTING AND SUSTAINING VAS, AND WILL LEAD TO SIGNIFICANT IMPROVEMENTS IN THE CLINICAL PROCEDURE OF VA ABLATION. COMPLETION OF THIS PROJECT WILL ALSO BE A MAJOR LEAP FORWARD IN THE INTEGRATION OF IMAGING, COMPUTATIONAL MODELING, INTRACARDIAC MAPPING, AND AL IN THE TREATMENT OF HEART RHYTHM DISORDERS.