Proceedings and Predictions in Cardiac Amyloidosis: Unsolved mysteries and challenges for the future

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Background

Cardiac amyloidosis (CA) is a progressive and often fatal disorder that may be greatly underdiagnosed and is certainly an underappreciated cause of heart failure. Almost all clinical cases of CA arise from either misfolded monoclonal immunoglobulin light chains (AL) from an abnormal clonal proliferation of plasma cells, or transthyretin amyloidosis (ATTR), a liver-synthesized protein normally involved in the transportation of the hormone thyroxine and retinol-binding protein. Clinical validation of non-invasive criteria for the diagnosis of ATTR-CA and the development of disease-modifying drugs has been shown to improve patients’ survival. Nowadays, the hardest challenge is the recognition of CA at early stages, but clinicians will have to deal with many grey areas and challenges in the future, including mechanisms of amyloid genesis, diagnosis, management, prognostic stratification, therapy and monitoring treatment response.

Recent years have been characterized by landmark advances in echocardiography, cardiac magnetic resonance, nuclear imaging and genetics, with a rapidly changing diagnostic and therapeutic landscape. CA is projected to exponentially increase in the future and addressing grey areas in clinical research will be paramount for patients’ management:

· Characterizing further biological mechanisms of the “amyloidogenic cascade”;

· Differentiating indolent “cardiac accumulation” associated with ageing from ATTR-CA;

· Detecting the minimal disease threshold to justify the initiation of novel treatments;

· Understanding the epidemiology of ATTR amyloidosis in the various clinical settings;

· Re-defining the paradigm of clinical management of comorbidities in CA

· Maximizing the application of cardiac magnetic resonance and nuclear imaging for diagnostic and prognostic purposes

Although current knowledge on amyloidosis has significantly improved, CA still represents a fascinating and challenging disease with many grey areas to address, from mechanisms of amyloidogenesis, to early recognition, prognostic stratification, and to monitoring of disease course and response to treatment.

The two main objectives of this Research Topic are: (1) to provide a comprehensive state-of-art of the current knowledge about CA from bench to bedside; (2) to stimulate researchers to share their experience in this field starting from current knowledge and to deal with future challenges in amyloidosis.

Keywords: Therapy, Cardiac Amyloidosis, Transthyretin, Light Chain, Epidemiology, Imaging

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