Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs

Adam Castaño, Brian M. Drachman, Daniel Judge, Mathew S. Maurer

Research output: Contribution to journalArticlepeer-review

Abstract

Transthyretin-cardiac amyloidoses (ATTR-CA) are an underdiagnosed but increasingly recognized cause of heart failure. Extracellular deposition of fibrillary proteins into tissues due to a variety of inherited transthyretin mutations in ATTRm or due to advanced age in ATTRwt eventually leads to organ failure. In the heart, amyloid deposition causes diastolic dysfunction, restrictive cardiomyopathy with progressive loss of systolic function, arrhythmias, and heart failure. While traditional treatments have consisted of conventional heart failure management and supportive care for systemic symptoms, numerous disease-modifying therapies have emerged over the past decade. From organ transplantation to transthyretin stabilizers (diflunisal, tafamidis, AG-1), TTR silencers (ALN-ATTR02, ISIS-TTR(Rx)), and degraders of amyloid fibrils (doxycycline/TUDCA), the potential for effective transthyretin amyloid therapy is greater now than ever before. In light of these multiple agents under investigation in human clinical trials, clinicians should be familiar with the systemic cardiac amyloidoses, their differing pathophysiology, natural histories, and unique treatment strategies.

Original languageEnglish (US)
Pages (from-to)163-178
Number of pages16
JournalHeart Failure Reviews
Volume20
Issue number2
DOIs
StatePublished - Mar 13 2015

Keywords

  • ALN-TTR02
  • ALN-TTRSc
  • Cardiac amyloidosis
  • Cardiomyopathy
  • Diflunisal
  • Doxycycline
  • Familial amyloid polyneuropathy
  • Oligonucleotides
  • Senile systemic amyloidosis
  • siRNA
  • Tafamidis
  • Transthyretin
  • TUDCA

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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