Prognosis of Transthyretin Cardiac Amyloidosis Without Heart Failure Symptoms

Esther Gonzalez-Lopez, Luis Escobar-Lopez, Laura Obici, Giulia Saturi, Mélanie Bezard, Sunil E. Saith, Omar F. AbouEzzeddine, Roberta Mussinelli, Christian Gagliardi, Mounira Kharoubi, Jan M. Griffin, Angela Dispenzieri, Silvia Vilches, Stefano Perlini, Simone Longhi, Silvia Oghina, Adrian Rivas, Martha Grogan, Mathew S. Maurer, Thibaud DamyGiovanni Palladini, Claudio Rapezzi, Pablo Garcia-Pavia

Research output: Contribution to journalArticlepeer-review


Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a treatable cause of heart failure (HF). Advances in diagnosis and therapy have increased the number of patients diagnosed at early stages, but prognostic data on patients without HF symptoms are lacking. Moreover, it is unknown whether asymptomatic patients benefit from early initiation of transthyretin (TTR) stabilizers. Objectives: The aim of this study was to describe the natural history and prognosis of ATTR-CM in patients without HF symptoms. Methods: Clinical characteristics and outcomes of patients with ATTR-CM without HF symptoms were retrospectively collected at 6 international amyloidosis centers. Results: A total of 118 patients (78.8% men, median age 66 years [IQR: 53.8-75 years], 68 [57.6%] with variant transthyretin amyloidosis, mean left ventricular ejection fraction 60.5% ± 9.9%, mean left ventricular wall thickness 15.4 ± 3.1 mm, and 53 [45%] treated with TTR stabilizers at baseline or during follow-up) were included. During a median follow-up period of 3.7 years (IQR: 1-6 years), 38 patients developed HF symptoms (23 New York Heart Association functional class II and 14 functional class III or IV), 32 died, and 2 required cardiac transplantation. Additionally, 20 patients received pacemakers, 13 developed AF, and 1 had a stroke. Overall survival was 96.5% (95% CI: 91%-99%), 90.4% (95% CI: 82%-95%), and 82% (95% CI: 71%-89%) at 1, 3, and 5 years, respectively. Treatment with TTR stabilizers was associated with improved survival (HR: 0.31; 95% CI: 0.12-0.82; P = 0.019) and remained significant after adjusting for sex, age, ATTR-CM type, and estimated glomerular filtration rate (HR: 0.18; 95% CI: 0.06-0.55; P = 0.002). Conclusions: After a median follow-up period of 3.7 years, 1 in 3 patients with asymptomatic ATTR-CM developed HF symptoms, and nearly as many died or required cardiac transplantation. Treatment with TTR stabilizers was associated with improved prognosis.

Original languageEnglish (US)
Pages (from-to)442-454
Number of pages13
JournalJACC: CardioOncology
Issue number4
StatePublished - Nov 2022


  • cardiac amyloidosis
  • early stages
  • heart failure
  • stabilizers
  • transthyretin

ASJC Scopus subject areas

  • Oncology
  • Cardiology and Cardiovascular Medicine


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