Heart failure & cardiomyopathies
Proteomics Profiling Reveals Molecular Subtypes of Transthyretin Cardiac Amyloidosis
Authors' conclusion
Our prospective cohort study using comprehensive plasma proteomics profiling not only uncovered molecular ATTR-CA subtypes but also identified pathogenetic mechanisms associated with differential prognosis and estimated the treatment effect of tafamidis.
Study context
- Population
- Patients with transthyretin cardiac amyloidosis (ATTR-CA) enrolled at Columbia Universitypatients eligible for analysis, 96 received tafamidis · subtype A 49 · subtype B 38 · subtype C 55
- Participants
- 142 patients
- Exposure
- all-cause mortality risk and estimated treatment effect of tafamidis among the identified molecular subtypes
- subtype An = 49
- subtype Bn = 38
- subtype Cn = 55reference
Methodological detailsunsupervised machine learning, comprehensive plasma proteomics profiling of 7289 proteins
- Unsupervised machine learning
- Comprehensive plasma proteomics profiling of 7289 proteins
Main finding
As reported in the abstract
Survival across molecular subtypes · median follow-up of 5.2 years
Different survival risks (log-rank)
P =0.035
Observational data: associations, not effects.
Further findings
| Outcome | Adjusted hazard ratio | P value | |
|---|---|---|---|
| All-cause mortality | 1.95 (95% CI 1.03–3.66) | P = 0.04 | |
| Mortality, tafamidis vs no tafamidis within subtype A · within subtype A; largest treatment effect | 0.24 (CI 0.10–0.55) | ||
| 0.10.31310Adjusted hazard ratio (log scale) |
- All-cause mortality: Mortality risk highest in subtype A, followed by B and then C
- All-cause mortality: adjusted for age, sex, TTR genotype, and concomitant medication use
- Mortality, tafamidis vs no tafamidis within subtype A: P for interaction=0.001
Pathway analysis, subtype A
- Subtype A had dysregulation of Ras/MAPK (mitogen-activated protein kinase) pathways, pathways implicated in ATTR-CA pathogenesis, and metabolic/inflammatory pathways
Original publication
Proteomics Profiling Reveals Molecular Subtypes of Transthyretin Cardiac Amyloidosis. Circ Heart Fail. Published 10 September 2026. doi:10.
Summarised from the published abstract; every number is checked against it