Systemic forms of amyloidosis affecting the heart are mostly light-chain (AL) and transthyretin (ATTR) amyloidoses. The latter is caused by deposition of misfolded transthyretin, either in wild-type (ATTRwt) or mutant (ATTRv) conformation. For diagnostics, specific serum biomarkers and modern non-invasive imaging techniques, such as cardiovascular magnetic resonance imaging (CMR) and scintigraphic methods, are available today. These imaging techniques do not only complement conventional echocardiography, but also allow for accurate assessment of the extent of cardiac involvement, in addition to diagnosing cardiac amyloidosis. Endomyocardial biopsy still plays a major role in the histopathological diagnosis and subtyping of cardiac amyloidosis. The main objective of the diagnostic algorithm outlined in this position statement is to detect cardiac amyloidosis as reliably and early as possible, to accurately determine its extent, and to reliably identify the underlying subtype of amyloidosis, thereby enabling subsequent targeted treatment.

HF patients exhibit cognitive deficits in the domains of attention and memory. MTA but not white matter lesion load seems to be related to cognitive impairment.

he term systemic amyloidosis embraces a number of heterogeneous syndromes characterized by protein deposits in the form of insoluble fibrils in the patient's tissues (1). The clinical findings vary according to the identity of the protein concerned and the extent and pattern of organ involvement (1, 2). As yet there are no valid epidemiological data for systemic amyloidosis in Germany. Light chain (AL) amyloidosis is so far considered to be the most frequently occurring form (1, 3), with an incidence of 8.9-12.7/million person-years and prevalence of 40-58/million person-years (4). Hereditary transthyretin (ATTRv) amyloidosis is estimated to affect 5000-10 000 persons worldwide ( 5). These figures meet the definition of a rare disease. In contrast, age-related wild-type transthyretin (ATTRwt) amyloidosis is being diagnosed increasingly often: 25% of patients with heart failure with preserved left ventricular ejection fraction (HFpEF) over 80 and 13% of those over 60 years of age are thought to be affected (6,7). This means that the prevalence has been underestimated.This article reviews the data on systemic amyloidosis, focusing on the prognostic relevance of cardiac involvement, on diagnosis of the disease, and on the spectrum of emerging treatment concepts. MethodsWe carried out a selective search of PubMed for pertinent records published in the period 2005-2019. The search terms were "systemic amyloidosis," "AL amyloidosis," "ATTR amyloidosis," "senile systemic amyloidosis," "cardiac amyloidosis," "familial amyloid polyneuropathy," and "familial amyloid cardiomyopathy." PathophysiologySystemic amyloidosis arises from the formation of insoluble amyloid fibrils, which in turn results from deposition of misfolded proteins. Over 30 proteins are known to be involved (8), causing different subtypes that cannot be distinguished by clinical means.• AL amyloidosis: This results from the deposition of monoclonal free light chains-systemically due to monoclonal gammopathy, multiple myeloma, or, more rarely, B-cell lymphoma, or locally due to local production of light chains. In systemic manifestations, circulating light chains have a direct cardiotoxic action (1). Deposits of light chains lead to mechanical interference and have cytotoxic and proapoptotic effects (1).

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