Cardiac Safety Committee

Mission Statement

The mission of the HESI Cardiac Safety Committee is to improve public health by reducing unanticipated cardiovascular-related adverse effects from drugs or chemicals, and to develop innovative approaches to support early detection and prediction as well as improved understanding of cardiovascular toxicology and pathobiology.

Cardiac Safety Early Career Seminar Award Series

The HESI Cardiac Safety Committee seeks Postdoctoral or Early Career Researchers working in cardiovascular safety science or a related field for the 2023 Early Career Seminar Award Series. This award offers an opportunity to share your research, learn from and network with experts in the toxicology and safety pharmacology fields from academia, regulatory agencies and pharmaceutical companies.

  • Award: Selected candidates will receive a $500.00 USD award and be invited to present their research on a public webinar with HESI Cardiac Safety Committee scientists and other invited guests. Webinar dates will be scheduled with the awardees in Q1 2023.
  • Qualifications and Requirements: Eligible candidates must have a PhD or equivalent degree in biology or related field (cell biology, biochemistry, pathology, biomechanical engineering, or similar); have current post-doc position/appointment or consider themselves an early career scientist (~1-5 years post-academic training) and may not have previously received an award under this program. Open to both domestic and international applicants.
  • Application: Submission cycle has closed for this award.

Working Groups

  • Stem Cell Working Group

    This group is working to understand and characterize use of stem cell–derived cardiomyocytes in cardiac safety assessments. An article that included best practices for use of stem cell cardiomyocytes in cardiac safety assessments was published in Regulatory Toxicology and Pharmacology. A new group is planning a study to explore in vitro assay ability to detect cardiotoxicity.

    Leadership Team:
    Ksenia Blinova, PhD (US Food and Drug Administration)
    Godfrey Smith, PhD (University of Glasgow)

    HESI Staff:
    Jennifer Pierson, MPH

  • Pro-Arrhythmia Working Group

    This working group is dedicated to investigating mechanisms of proarrhythmic risk. They continue to collaborate with the CiPA Initiative and ICH, and recently published its anticipated high throughput systems (HTS) ion channel work. A new subteam is scoping a conduction/ sodium channel paper to discuss the history and challenges surrounding this topic.

    A 3-phased project was conducted by the HESI Pro-Arrhythmia Working Group starting with a detailed literature review and followed by a collaborative HESI-FDA database of 150 new drug candidates to evaluate how predictive nonclinical studies are to clinical outcomes.

    • Related Publication: The Challenges of Predicting Drug-Induced QTc Prolongation in Humans. Jean-Pierre Valentin, Peter Hoffmann, Catherine Ortemann-Renon, John Koerner, Jennifer Pierson, Gary Gintant, James Willard, Christine Garnett, Matthew Skinner, Hugo M Vargas, Todd Wisialowski, Michael K Pugsley. Toxicological Sciences. 11 February 2022

     

    Leadership Team:
    Jose Vicente Ruize, PhD (US Food and Drug Administration)
    Jean-Pierre Valentin, PhD (UCB Biopharma)

    HESI Staff:
    Jennifer Pierson, MPH

  • Integrative Strategies Working Group

    This working group has examined the sensitivity within a preclinical species to assess the function of contractility. They continue their partnership with University of Surrey and Imperial College London on a mathematical model to predict blood pressure changes. The Implanted Telemetry Subteam explored the impact of telemetry lead placement in toxicology studies (a collaboration with the Pro-Arrhythmia Working Group).

    Leadership Team:
    Michael Pugsley, PhD (Cytokinetics)
    Sandy Eldridge, PhD (National Cancer Institute)

    HESI Staff:
    E’Lissa Flores, PhD

  • Cardiac Biomarkers Working Group

    This working group is dedicated to investigating preclinical cardiac biomarkers of hypercoagulability induced under a thrombotic state, in both normal and diseased states. A manuscript was submitted detailing a study investigating the effects of doxorubicin in Zucker diabetic fatty rats. A new study is in the planning stages using xenobiotics to induce the procoagulant state and confirm measurements of biomarkers of interest.

    Leadership Team:
    Eric Schultze, PhD (Eli Lilly & Company)
    Marjory Brooks, DVM (Cornell University)

    HESI Staff:
    E’Lissa Flores, PhD

  • Cardiac Compound Tool (CCT) Database Subteam

    The Cardiac Safety Steering Team established this new subteam in early 2020 to develop and provide a structured resource for use when identifying compounds appropriate in a planned committee study. Delivery of this publicly accessible database is anticipated by the end of 2022.

    HESI Staff:
    Jennifer Pierson, MPH

  • FDA U01 Validating Stem Cell Technology

    HESI has been awarded a multi-year U01 grant from the US FDA on the “Evaluation of Integrated Human-Relevant Approaches to Identify Drug Induced Cardiovascular Liabilities.” This grant supports HESI in funding and managing novel, in vitro experimental studies to develop targeted mechanistic data to inform drug safety assessment for key cardiac “failure modes.”

  • FDA BAA Ion Channel Patch Clamp Study

    HESI received a Broad Agency Announcement (BAA) award from the US FDA to manage a multi-site study on manual and automated patch clamp platforms. The original study included 4 ionic currents (hERG, Nav1.5 peak, Nav1.5 late and Cav1.2) and 14 compounds and has been expanded to include a total of 28 compounds. The project aims to collect additional information on inter-laboratory variability as well as support the FDA in silico model. Learn more about the recommended ion channel protocols and in silico model here.

HESI Staff

Leadership Team

  • Brian Berridge, DVM, PhD

    National Institute of Environmental Health Sciences, National Toxicology Program

  • Norman Stockbridge, MD, PhD

    US Food and Drug Administration

Committee Events

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HESI & SPS virtual training opportunity

June 21, 2022 – December 31, 2022

On Demand Training, HESI & SPS

The Health and Environmental Sciences Institute (HESI) & Safety Pharmacology Society (SPS) present a new, on-demand training opportunity: A closer look at the new ICH E14/S7B Q&A's and Training Materials.

Read more

HESI Cardiac Safety Early Career Webinar Series – Shagun Krishna

May 12, 2022

HESI Cardiac Safety Early Career Webinar Series, Virtual

The HESI Cardiac Safety Committee is pleased to announce the final webinar in their Early Career Seminar Award Series. This competitive award is given to postdoctoral or early career scientists who have compelling research related to cardiovascular safety and risk assessment, and the webinar series offers an opportunity for ...

Read more

HESI Cardiac Safety Early Career Webinar Series – Arvin Soepriatna, Brown University

April 8, 2022

HESI Cardiac Safety Early Career Webinar Series, Virtual

The HESI Cardiac Safety Committee is pleased to announce the second webinar in their Early Career Seminar Award Series. This competitive award is given to postdoctoral or early career scientists who have compelling research related to cardiovascular safety and risk assessment, and the webinar series offers an opportunity for ...

Read more

HESI Cardiac Safety Committee Annual Meeting

February 28, 2022 – March 1, 2022

Virtual, Internal Committee Meeting

The HESI Cardiac Safety Committee will convene their annual business meeting on 28 February and 1 March 2022. The mission of the HESI Cardiac Safety Committee is to improve public health by reducing unanticipated cardiovascular-related adverse effects from drugs or chemicals, and to develop innovative ...

Read more

HESI Cardiac Safety Early Career Webinar Series – Julia Hotek

February 11, 2022

HESI Cardiac Safety Early Career Webinar Series, Virtual

The Cardiac Safety Steering Team is proud to present the first webinar series featuring Early Career Seminar Series Awardees. Dr. Julia Hotek,  Associate Principal Scientist at Merck, will present: Understanding hemodynamic changes: Use of signal processing tools to advance preclinical blood pressure analysis.

Read more

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Committee Publications

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Considerations for an In Vitro, Cell-Based Testing Platform for Detection of Drug-Induced Inotropic Effects in Early Drug Development. Part 2: Designing and Fabricating Microsystems for Assaying Cardiac Contractility With Physiological Relevance Using Human iPSC-Cardiomyocytes

Frontiers in Pharmacology, 2019

Ribeiro A, Guth BD, Engwall M, Eldridge S, Foley CM, Guo L, ...

Contractility of the myocardium engines the pumping function of the heart and is enabled by the collective contractile activity of its muscle cells: cardiomyocytes. The effects of drugs on the contractility of human cardiomyocytes in vitro can provide mechanistic insight that can support the prediction of clinical cardiac drug ...

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Considerations for an In Vitro, Cell-Based Testing Platform for Detection of Adverse Drug-Induced Inotropic Effects in Early Drug Development. Part 1: General Considerations for Development of Novel Testing Platforms

Frontiers in Pharmacology, 2019

Guth BD, Engwall M, Eldridge S, Foley CM, Guo L, Gintant G, ...
  • HESI - Health and Environmental Sciences Institute

Drug-induced effects on cardiac contractility can be assessed through the measurement of the maximal rate of pressure increase in the left ventricle (LVdP/dtmax) in conscious animals, and such studies are often conducted at the late stage of preclinical drug development. Detection of such effects earlier in drug research using ...

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Assessing drug-induced long QT and proarrhythmic risk using human stem cell-derived cardiomyocytes in a Ca2+ imaging assay: Evaluation of 28 CiPA compounds at three test sites

Toxicological Sciences, 2019

Hua Rong Lu, Haoyu Zeng, Ralf Kettenhofen, Liang Guo, ...
  • HESI - Health and Environmental Sciences Institute

A consortium, multi-site approach to testing in vitro assay technology for prediction of drug-induced TdP. The authors sought to test calcium transient assays using the CiPA 28 drugs.

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A Proof-of-Concept Evaluation of JTPc and Tp-Tec as Proarrhythmia Biomarkers in Preclinical Species: A Retrospective Analysis by an HESI-Sponsored Consortium

International Journal of Toxicology, 2018

Emmanuel Boulay, Matthew M. Abernathy, Ray Chu, ...
  • HESI - Health and Environmental Sciences Institute

Results from this limited retrospective electrocardiogram analysis suggest that JTpca and Tpeca may discriminate selective IKr blockers and multichannel blockers and could be considered in the context of an integrated comprehensive proarrhythmic risk assessment.

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