ArticlebioRxiv : the preprint server for biology2026
Predicting Sex-Specific Antiarrhythmic Strategies for Atrial Fibrillation through a Regression-Guided Computational Modeling Pipeline.
Nathaniel T Herrera, Haibo Ni, Charlotte E R Smith, Yixuan Wu, Dobromir Dobrev, Stefano Morotti, Eleonora Grandi
Abstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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5 · Who and what moneyAuthors and funding
7 authors.
Nathaniel T HerreraDepartment of Pharmacology, University of California Davis, Davis, California, United States.
Haibo NiDepartment of Pharmacology, University of California Davis, Davis, California, United States.
Charlotte E R SmithDepartment of Pharmacology, University of California Davis, Davis, California, United States.
Yixuan WuDepartment of Pharmacology, University of California Davis, Davis, California, United States.
Dobromir DobrevInstitute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany.
Stefano MorottiDepartment of Pharmacology, University of California Davis, Davis, California, United States.
Eleonora GrandiDepartment of Pharmacology, University of California Davis, Davis, California, United States.ORCID 0000-0002-4401-8857 Funding
Project 3 (Mercola)P01HL141084 · NHLBI · STANFORD UNIVERSITY · PI Joseph C. Wu · 2019 to 2026
$21.1MThe Role of Inflammasome in the Pathogenesis of Atrial FibrillationR01HL136389 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Na Li · 2017 to 2026
$5.6MSex-specific arrhythmogenic mechanisms of atrial fibrillationR01HL131517 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Eleonora Grandi · 2016 to 2026
$5.0MFunctional Microdomains in the Heart's Pacemaker: A New Dimension of Cardiac RemodelingR01HL141214 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Alexey V Glukhov · 2018 to 2026
$3.8MMultiomics and Functional Characterization Establish Druggable Targets for PVC-Driven Idiopathic VFR01HL170521 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Lee Lochbaum Eckhardt, Eleonora Grandi · 2023 to 2026
$3.1MResolution of inflammation and atrial fibrillationR01HL165704 · NHLBI · UNIVERSITY OF MINNESOTA · PI SAMUEL C DUDLEY · 2023 to 2026
$2.9MCardiac fibroblast inflammasome and atrial myopathyR01HL163277 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI LI, NA · 2022 to 2025
$2.8MRole of Nucleoside-Diphosphate Kinase Signaling in Atrial FibrillationR01HL160992 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Xander H.T. Wehrens · 2023 to 2026
$2.1MPhosphodiesterase 1 (PDE1) Regulation of Myocardial Calcium and FunctionR01HL171586 · NHLBI · LOYOLA UNIVERSITY CHICAGO · PI Grace Kim Muller · 2024 to 2026
$1.9MPhenotype-specific models, mechanisms, and treatment of HFpEFR01HL171057 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Stefano Morotti · 2024 to 2026
$1.8MFKBP5 AND CARDIAC ARRHYTHMOGENESISR01HL164838 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Na Li · 2024 to 2026
$1.7MCalcium Driven Fibroblast Dysregulation in Human Atrial Profibrotic RemodelingR01HL176651 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Eleonora Grandi · 2025 to 2026
$1.1MNHLBI NIH HHS P01 HL141084NHLBI NIH HHS R00 HL138160NHLBI NIH HHS R01 HL131517NHLBI NIH HHS R01 HL136389NHLBI NIH HHS R01 HL141214NHLBI NIH HHS R01 HL160992NHLBI NIH HHS R01 HL163277NHLBI NIH HHS R01 HL164838NHLBI NIH HHS R01 HL165704NHLBI NIH HHS R01 HL170521NHLBI NIH HHS R01 HL171057NHLBI NIH HHS R01 HL171586NHLBI NIH HHS R01 HL176651NIA NIH HHS R03 AG086695
6 · The paper itselfAbstract
Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is a major contributor to stroke, heart failure, and mortality worldwide. Although AF affects both men and women at a similar rate, accumulating experimental and clinical evidence indicates that its underlying mechanisms, disease progression, and treatment responses differ by sex. However, current antiarrhythmic drug development and clinical management of AF remains largely sex neutral, likely contributing to limited efficacy and increased adverse effects. To address this gap, we developed a computational drug-screening pipeline based on experimentally constrained, sex-specific human atrial cardiomyocyte models to predict and evaluate sex-specific pharmacological strategies for AF. The pipeline integrates multivariable regression with mechanistic modeling to systematically test multi-target combinations of ion channel inhibitors and Ca
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PMID41727027
PMCPMC12919104
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