Advances in pharmacotherapy for cardiac amyloidosis

ABSTRACT

Introduction

Amyloidosis is a group of progressive and devastating disorders resulting from extracellular deposition of misfolded proteins into tissues. When deposition of fibrils occurs in cardiac tissues, this systemic disease can lead to a very poor prognosis. Systemic amyloidosis can be acquired [light chain (AL) amyloidosis; AA amyloidosis], or hereditary [transthyretin (ATTR) amyloidosis]. Cardiac disease in amyloidosis is usually secondary to a systemic disease. The diagnosis of cardiac involvement is often delayed and yields an adverse prognosis.

Areas covered

in this review, the authors report current literature on advances in pharmacotherapy for cardiac amyloidosis, mainly focused on AL and ATTR amyloidosis treatment.

Expert opinion

Most pharmacological trials in amyloidosis patients, both AL and TTR, are directed to study the effects of drugs on polyneuropathy. However, since cardiac involvement carries a prominent negative survival impact in amyloidosis patients, future research should be more focused on amyloidosis cardiomyopathy as primary endpoint. Additionally, in AL amyloidosis therapies are mainly derived from experience on multiple myeloma treatment. In this specific setting, possible future research could particularly focus on immunotherapeutic agents able to optimize the standard chemotherapy results and, thus, allowing a larger population of patients to be treated by bone marrow stem cell transplantation.

KEYWORDS:

• Amyloidosis
• cardiomyopathy
• drugs
• therapy
• light chain
• transthyretin

Article highlights

• Amyloidosis is a group of progressive and devastating disorders resulting from extracellular deposition of misfolded proteins into tissues.

• The diagnosis of cardiac involvement is often delayed and yields an adverse prognosis.

• The three main cardiac types of amyloidosis are monoclonal AL amyloidosis, hereditary TTR amyloidosis and wild-type amyloidosis (senile systemic amyloidosis – SSA).

• The first aim of therapy in AL amyloidosis is to eradicate the amyloidogenic plasma cell clone in order to block progression of end-organ damage.

• At present, treatment options for AL amyloidosis are largely based on data derived from treatment strategies adopted in multiple myeloma.

• Different new drugs have been developed for treatment of transthyretin amyloidosis. Some of them potentially interfere with amyloidogenic wild-type and mutated transthyretin production, others reduce the ensuing fibrils formation at different stages of disease.

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Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.