Drug-induced myocardial dysfunction - recommendations for assessment in clinical and pre-clinical studies

Area of Science:

• Cardiology
• Pharmacology
• Oncology

Background:

• Drug-induced myocardial dysfunction is a significant safety concern in drug development, particularly with oncology compounds.
• Mechanisms include decreased left ventricular ejection fraction and heart failure.
• Early detection and monitoring of cardiotoxicity are essential.

Purpose of the Study:

• To provide an overview of cardiovascular imaging modalities and cardiac biomarkers for monitoring cardiac function.
• To offer practical guidance for the early detection and monitoring of drug-induced cardiotoxicity in drug development.
• To highlight the role of these tools in managing risks associated with new therapeutic agents.

Main Methods:

• Review of cardiovascular imaging techniques, including echocardiography and cardiac magnetic resonance imaging (CMR).
• Discussion of cardiac serologic biomarkers, such as troponins and B-type natriuretic peptides.
• Integration of imaging and biomarker data for comprehensive cardiotoxicity assessment.

Main Results:

• Echocardiography is widely available, cost-effective, and radiation-free for initial assessment.
• Cardiac MRI offers superior reliability, reproducibility, and accuracy, with capabilities to assess myocardial edema, fibrosis, and necrosis.
• Biomarkers complement imaging, aiding in early detection and risk stratification.

Conclusions:

• Cardiovascular imaging and biomarkers are indispensable tools for the early detection and monitoring of drug-induced myocardial dysfunction.
• These methods are critical for developing mitigation strategies for potentially cardiotoxic drugs, especially in oncology.
• Strategic use of imaging and biomarkers supports safer drug development.