title: Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs.
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.
authors.affiliation: Center for Advanced Cardiac Care, Columbia College of Physicians and Surgeons, New York City, NY, USA, ac3220@cumc.columbia.edu.
authors.forename: Adam
authors.initials: A
authors.lastname: Castaño
authors.forename: Brian M
authors.initials: BM
authors.lastname: Drachman
authors.forename: Daniel
authors.initials: D
authors.lastname: Judge
authors.forename: Mathew S
authors.initials: MS
authors.lastname: Maurer
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis* / Q000628:therapy*; D001583:Benzoxazoles / Q000627:therapeutic use; D015415:Biomarkers; D009202:Cardiomyopathies / Q000628:therapy*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D017147:Defibrillators, Implantable; D004061:Diflunisal / Q000627:therapeutic use; D004318:Doxycycline / Q000627:therapeutic use; D006333:Heart Failure / Q000628:therapy*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D016377:Organ Transplantation; D010138:Pacemaker, Artificial; D034741:RNA, Small Interfering / Q000627:therapeutic use
chemical_list: D001583:Benzoxazoles; D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D004061:Diflunisal; C547076:tafamidis; D004318:Doxycycline