In preclinical drug development, accurate prediction of drug effects on the human heart is
critically important, whether in the context of cardiovascular safety or for the purpose of modulating
cardiac function to treat heart disease. Current strategies have significant limitations, whereby, cardiotoxic
drugs can escape detection or potential life-saving therapies are abandoned due to false positive
toxicity signals. Thus, new and more reliable translational approaches are urgently needed to help accelerate
the rate of new therapy development. Renewed efforts in the recovery of human donor hearts
for research and in cardiomyocyte isolation methods, are providing new opportunities for preclinical
studies in adult primary cardiomyocytes. These cells exhibit the native physiological and pharmacological
properties, overcoming the limitations presented by artificial cellular models, animal models and
have great potential for providing an excellent tool for preclinical drug testing. Adult human primary
cardiomyocytes have already shown utility in assessing drug-induced cardiotoxicity risk and helping in
the identification of new treatments for cardiac diseases, such as heart failure and atrial fibrillation.
Finally, strategies with actionable decision-making trees that rely on data derived from adult human
primary cardiomyocytes will provide the holistic insights necessary to accurately predict human heart
effects of drugs.
Keywords: Small molecule drug discovery, human heart, adult human primary cardiomyocytes, cardiotoxicity, atrial fibrillation,
heart failure, translational sciences.
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