title: New and Evolving Concepts Regarding the Prognosis and Treatment of Cardiac Amyloidosis.
abstract: Systemic amyloidoses are rare and proteiform diseases, caused by extracellular accumulation of insoluble misfolded fibrillar proteins. Prognosis is dictated by cardiac involvement, which is especially frequent in light chain (AL) and in transthyretin variants (ATTR, both mutated, (ATTRm), and wild-type, (ATTRwt)). Recently, ATTRwt has emerged as a potentially relevant cause of a heart failure with preserved ejection fraction (HFpEF). Cardiac amyloidosis is an archetypal example of restrictive cardiomyopathy, with signs and symptoms of global heart failure and diastolic dysfunction. Independent of the aetiology, cardiac amyloidosis is associated with left ventricular concentric "hypertrophy" (i.e. increased wall thickness), preserved (or mildly depressed) ejection fraction, reduced midwall fractional shortening and global longitudinal function, as well as evident diastolic dysfunction, up to an overly restrictive pattern of the left ventricular filling. Cardiac biomarkers such as troponins and natriuretic peptides are very robust and widely accepted diagnostic as well as prognostic tools. Owing to its dismal prognosis, accurate and early diagnosis is mandatory and potentially life-saving. Although pathogenesis is still not completely understood, direct cardiomyocyte toxicity of the amyloidogenic precursor proteins and/or oligomer aggregates adds on tissue architecture disruption caused by amyloid deposition. The clarification of mechanisms of cardiac damage is offering new potential therapeutic targets, and several treatment options with a relevant impact on prognosis are now available.
authors.affiliation: Clinica Medica II, Department of Internal Medicine, University of Pavia, P. le Golgi 19, 27100, Pavia, Italy. stefano.perlini@unipv.it.|Amyloidosis Research and Treatment Center, Fondazione Policlinico IRCCS San Matteo, University of Pavia, P. le Golgi 19, 27100, Pavia, Italy. stefano.perlini@unipv.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Perlini
authors.affiliation: Clinica Medica II, Department of Internal Medicine, University of Pavia, P. le Golgi 19, 27100, Pavia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Mussinelli
authors.affiliation: Clinica Medica II, Department of Internal Medicine, University of Pavia, P. le Golgi 19, 27100, Pavia, Italy.|Experimental Medicine PhD Program, University of Pavia, Pavia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Salinaro
mesh_terms: D000686:Amyloidosis / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D009202:Cardiomyopathies / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology; D045265:Natriuretic Peptides / Q000097:blood; D011228:Prealbumin / Q000235:genetics; D011379:Prognosis; D013318:Stroke Volume; D014336:Troponin / Q000097:blood
chemical_list: D045265:Natriuretic Peptides; D011228:Prealbumin; D014336:Troponin
keywords: Cardiac amyloidosis; Cardiac imaging; Cardiac toxicity; Diastolic function; Heart failure; NT-proBNP; Systolic function