*2.4.1.6 Endocrine/metabolic disorders*

*Visions of Cardiomyocyte - Fundamental Concepts of Heart Life and Disease*

toxic cardiomyopathy are summarized in **Figure 2**.

and elevation of left and/or biventricular filling pressure [26].

Several, systemic diseases may infiltrate the myocardium and result in DCM. Sarcoidosis, iron overload, and amyloidosis represent the most common clinical entities. Sarcoidosis is a multisystem inflammatory disease of unknown origin characterized by non-caseating granulomas in multiple organs. Sarcoidosis can progress to a fibrotic stage leading to DCM [26]. In the setting of iron overload, such as hereditary hematochromatosis, high blood volume, or parenteral iron infusions,

*2.4.1.4 Arrhythmia-induced DCM*

*2.4.1.5 Infiltrative diseases*

which can occur 10–30 years after exposure. Both chronic forms tend to be irreversible, are dosage dependent and are associated with ultrastructural changes in the cardiac myocytes [40]. Trastuzumab, a monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2), is wildly used and very effective for the treatment of HER2-positive breast cancer. HER2 receptors are also localized on the cardiomyocyte. The inhibition of the Her2:Her4 signaling process in the myocardium is principally responsible for the cardiotoxicity [26]. In addition, a number of other, non-chemotherapeutical medications are associated with DCM, such as cyclophosphamide, phenothiazines, antidepressant drugs, carbon monoxide, lead, lithium, pseudoephedrine, ephedrine, cobalt, anabolic steroids, hydroxychloroquine, clozapine, and catecholamines [38, 41]. Possible causes of

Tachycardia-induced cardiomyopathy was described more than 100 years ago by Gossage et al. as a reversible form of systolic dysfunction caused by long-lasting supraventricular or ventricular arrhythmias [42]. Ongoing rapid atrial or ventricular pacing may result in systemic changes by neurohormonal activation, characterized by reduction in serum sodium, activation of the renin-angiotensin system, and an increase of plasma atrial natriuretic peptide, aldosterone, and norepinephrine. Abnormal myocardial and cellular remodeling occurs, which may result in DCM. Furthermore, epinephrine can also lead to abnormal myocardial and cellular remodeling, which further result in biventricular dilatation, decreased contractility,

**44**

**Figure 2.**

*Reasons for toxic cardiomyopathies.*

Endocrinologic disorders rarely lead to the phenotype of DCM. Especially thyroid hormones have a significant impact on cardiac function and structure via regulation and expression of key structural and regulatory genes like myosin heavy chain and phospholamban. Therefore, excess or deficiency of triiodothyronine (T3) may lead to DCM in a late stage [45]. Growth hormone disorders, pheochromocytoma, and Cushing's disease are also very rare causes of DCM [26, 46]. Furthermore, the literature names nutritional deficiencies of thiamine (beriberi disease), selenium (Keshan disease), and l-carnitine being responsible for DCM [47, 48].
