A translational approach to detecting drug-induced cardiac injury with cardiac troponins: consensus and recommendations from the Cardiac Troponins Biomarker Working Group of the Health and Environmental Sciences Institute.
Cardiac troponins (cTns) are established biomarkers of ischemic heart disease in humans. However, their value as biomarkers of cardiac injury from causes other than ischemic heart disease is now being explored, particularly in drug development. In a workshop sponsored by the Cardiac Troponin Biomarker Working Group of the Health and Environmental Sciences Institute, preclinical, clinical, and regulatory scientists discussed the application of cTns in their respective environments, issues in translating the preclinical application of cTn to clinical studies, and gaps in our understanding of cTn biology and pathobiology. Evidence indicates that cTns are sensitive and specific biomarkers of cardiac injury from varying causes in both animals and humans. Accordingly, monitoring cTns can help ensure patient safety during the clinical evaluation of new drugs. In addition, preclinical characterization of cardiac risk and cTns as biomarkers of that risk can guide relevant clinical application and interpretation. We summarize here the outcomes of the workshop which included consensus statements, recommendations for further research, and a proposal for a cross-disciplinary group of clinical, regulatory, and drug development scientists to collaborate in such research.
Berridge
Brian R
BR
GlaxoSmithKline Safety Assessment, 5 Moore Drive, Research Triangle Park, NC, USA. brian.x.berridge@gsk.com
Pettit
Syril
S
Walker
Dana B
DB
Jaffe
Alan S
AS
Schultze
Albert E
AE
Herman
Eugene
E
Reagan
William J
WJ
Lipshultz
Steven E
SE
Apple
Fred S
FS
York
Malcolm J
MJ
D000818:Animals; D009202:Cardiomyopathies / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis*; D002986:Clinical Trials as Topic; D003299:Cooperative Behavior; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D004493:Education; D006801:Humans; D033183:Interdisciplinary Communication; D008991:Monitoring, Physiologic; D011237:Predictive Value of Tests; D018570:Risk Assessment; D014336:Troponin / Q000097:blood*
D014336:Troponin