Heart failure & cardiomyopathies
Cascade genetic screening in families with hereditary transthyretin amyloidosis: diagnostic and prognostic impact
Authors' conclusion
Cascade genetic screening facilitated earlier diagnosis and was associated with improved survival, likely related to identification at an earlier stage of disease and timely treatment initiation.
Study context
- Population
- Families with hereditary transthyretin amyloidosis (ATTRv), 2004–2024431 families
- Participants
- 967 participants
- Exposure
- Index vs G+/P+ vs G+/P-
- Indexn = 398reference
- G+/P+n = 108
- G+/P-n = 461
- Outcome
- Clinical characteristics, disease conversion and survival
Methodological detailsmulticentre, 15 Italian referral centres, Genetic screening of 1243 relatives identified 569 carriers
- Multicentre
- 15 Italian referral centres
- Genetic screening of 1243 relatives identified 569 carriers
Main finding
As reported in the abstract
Conversion to clinical ATTRv among G+/P- carriers · median follow-up 5.3 [1.7-9.8] years
| Group | Value | Glu89Gln | Phe64Leu | Val30Met | Ile68Leu | Val122Ile | Other variants |
|---|---|---|---|---|---|---|---|
| G+/P- | 16.7% | 42.2% (95% CI 28.8-56.9) | 24.7% (95% CI 16.1-35.8) | 13.1% (95% CI 7.4-22.1) | 7.3% (95% CI 4.1-12.8) | 5.1% (95% CI 1.3-18.3) | 22.9% (95% CI 14.5-34.1) |
G+/P-
Value16.7%
Glu89Gln42.2% (95% CI 28.8-56.9)
Phe64Leu24.7% (95% CI 16.1-35.8)
Val30Met13.1% (95% CI 7.4-22.1)
Ile68Leu7.3% (95% CI 4.1-12.8)
Val122Ile5.1% (95% CI 1.3-18.3)
Other variants22.9% (95% CI 14.5-34.1)
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| Survival | 0.43 (0.24–0.79) | |
| Mortality with disease-modifying therapy · independently associated | 0.11 (0.01–0.17) | |
| 0.050.21520Hazard ratio (log scale) |
Survival
- Mixed phenotype showed worse outcomes than cardiac presentations
Conversion >10 years earlier than predicted age of onset
- Carriers converting >10 years earlier than predicted
- 11/62 (17.7%)
Original publication
Cascade genetic screening in families with hereditary transthyretin amyloidosis: diagnostic and prognostic impact. Eur Heart J. Published 7 April 2026. doi:10.
Summarised from the published abstract; every number is checked against it