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Newer Therapies for Amyloid Cardiomyopathy

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source: Current Heart Failure Reports

year: 2016

authors: Chakraborty R, Muchtar E, Gertz MA

summary/abstract:

The heart and the kidneys are the most commonly involved organs in systemic amyloidosis. Cardiac involvement is associated with an increased morbidity, treatment intolerance, and poorer overall survival. The most common types of amyloidosis that are associated with cardiac involvement include light chain (AL) amyloidosis and transthyretin (TTR) amyloidosis (both mutant and wild type).

The traditional first-line treatment for AL amyloidosis includes alkylator-based chemotherapy or high-dose melphalan followed by autologous stem cell transplantation (ASCT). Novel agents, including proteasome inhibitors, immunomodulators, and monoclonal antibodies, have shown promising activity in both frontline and relapsed settings.

Orthotopic heart transplantation (OHT) followed by ASCT has led to superior outcomes compared to OHT alone. Orthotopic liver transplantation (OLT) is the first-line treatment for TTR amyloidosis. However, progression of cardiac amyloidosis after OLT is often noted due to deposition of wild TTR. Combined OLT and OHT also has a role in treatment and leads to superior outcomes in carefully selected candidates. Pharmacologic agents, including diflunisal, tafamidis, small interfering ribonucleic acid, and doxycycline, have shown promising activity in stabilizing TTR from misfolding into fibrils and are being actively investigated.

Best supportive care and management of heart failure symptoms with diuretics are a mainstay of treatment in all cardiac amyloidosis subtypes. Robust data on the benefit of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta blockers in amyloid cardiomyopathy is lacking.

organization: Mayo Clinic,USA

DOI: 10.1007/s11897-016-0300-1

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