S08-02 Current and emerging concepts of cardiotoxicity: applicability inrisk assessment for regulatory purposes

Abstract

Cardiomyopathy is a myocardial disorder. The heart muscle is structurally affected and/or functions abnormally, and in many cases, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease. Before clinicians conclude their diagnosis on idiopathic cardiomyopathy, toxic as well as viral and immune causes should also be considered.

For some medication, such as anticancer drugs, epidemiological studies point to cardiotoxic manifestations. Other implications related to specific cardiovascular drugs (e.g. calcium-channel blockers, beta-blockers) are mostly associated in overdose with acute heart failure ^[1].

Industrial chemicals can exert toxic action, directly or indirectly, on various components of the cardiovascular system. Cardiotoxins (e.g. plant glycosides from oleander, foxglove and lily) can alter the heart functionally or structurally depending on the dosage and exposure period. The main molecular targets of the toxins in the heart are sodium, potassium and calcium channels ^[2]. Oxidative stress plays also a crucial role in cardiac toxicity caused by industrial chemicals, like mercury. Metals like platinum, cause direct injury on the myocytes, and cause mitochondrial ultrastructural abnormalities and platelet activation and aggregation. Cobalt-related cardiomyopathy probably results from interference with energy production and contractile mechanisms, but additional factors (nutrition, hypothyroidism) are often implicated. Nanoparticles are known to affect the heart through oxidative stress and inflammation, cellular apoptosis and decreased cell proliferation, decreased heart rate and down regulation of genes functioning in heart formation and development. The aetiology of ethanol-related cardiotoxicity is multifactorial, with individual susceptibility being important. The true prevalence of toxins/ chemicals related-dilated cardiomyopathy in the general population is not known.