Novel strategies for the diagnosis and treatment of cardiac amyloidosis

Abstract

Systemic amyloidoses are rare, complex diseases caused by misfolding of autologous protein. The presence of heart involvement is the most important prognostic determinant. The diagnosis of amyloid cardiac involvement relies on echocardiography and magnetic resonance imaging, while scintigraphy with bone tracers is helpful in differentiating light chain amyloidosis from other types of amyloidosis involving the heart. Although these diseases are fatal, effective treatments exist that can alter their natural history, provided that they are started before irreversible cardiac damage has occurred. Refined diagnostic techniques, accurate patients’ stratification based on biomarkers of cardiac dysfunction, the availability of novel, more powerful drugs, and ultimately, the unveiling of the cellular mechanisms of cardiac damage created a favorable environment for a dramatic improvement in the treatment of this disease that we expect in the next few years.

Keywords:

• amyloidosis
• biomarkers
• cardiac toxicity
• chemotherapy
• diagnosis
• RNA-targeted therapy

Financial & competing interests disclosure

This study was supported in part by a grant from the ‘Associazione Italiana per la Ricerca sul Cancro – Special Program Molecular Clinical Oncology 5 per mille n. 9965’ and from CARIPLO ‘Structure-function relation of amyloid: understanding the molecular bases of protein misfolding diseases to design new treatments n. 2013-0964’. G Merlini is a consultant for Millenium Pharmaceuticals, Inc, Pfizer, Janssen, Prothena and ISIS. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The diagnosis of amyloid cardiac involvement is based on the sensitive biomarker N-terminal pro-natriuretic type B and several imaging technologies.

• Treatment of cardiac amyloidoses is based on early and correct diagnosis, including unequivocal typing.

• Cardiac involvement can be recognized at a pre-symptomatic, reversible stage with screening programs based on biomarkers of organ damage in patients at risk.

• Treatment should be risk-adapted based on validated staging systems, with frequent assessments of efficacy.

• Standards of care still need to be established, and patients should be treated in the framework of clinical trials.

• Novel treatment approaches aimed at interfering with the amyloidogenic process, targeting the amyloid deposits and inhibiting newly discovered pathways of organ damage are emerging and will likely be used in combination with classical approaches aimed at reducing the availability of the amyloidogenic precursors.

• Supportive therapy is vital, but must be cautiously given due to systemic involvement.

Notes