Overview
Autosomal dominant excess of transthyretin (ATTR) leads to the formation of misfolded TTR fibrils that deposit in various organs, causing significant morbidity and mortality, particularly in cardiac and neurologic contexts 13.Diagnosis
Key Diagnostic Criteria: Presence of cardiac tracer uptake in bone scintigraphy or transthyretin-positive cardiac biopsy 2.
Recommended Tests: Electrocardiogram (ECG), echocardiogram, and laboratory tests for initial screening 2.
Serial Evaluation: Essential for monitoring disease progression, especially in high-risk familial cohorts 2.Management
First-Line Treatments:
- TTR Stabilizers: Drugs like tafamidis stabilize TTR, reducing amyloid deposition 1.
- TTR Gene Silencers: Antisense oligonucleotides such as patisiran and inotersen reduce TTR production 1.
Adjunctive Treatments: Specific adjunctive therapies are not extensively detailed in the provided abstracts, focusing primarily on pharmacological interventions 1.Special Populations
Elderly: Higher prevalence of cardiac amyloidosis noted in elderly patients with conditions like hypertrophic cardiomyopathy and aortic stenosis 3.
Comorbidities: Patients with heart failure with preserved ejection fraction and aortic stenosis are at increased risk 3.Key Recommendations
Use of TTR Stabilizers or Gene Silencers Significantly Reduces Mortality: Both TTR stabilizers and gene silencers effectively reduce all-cause mortality in ATTR patients compared to placebo (Evidence: Strong 1).
Regular Screening for Familial ATTR: Implement systematic screening for relatives of ATTR patients, particularly within 10 years before predicted disease onset, using ECG, echocardiogram, and laboratory tests (Evidence: Moderate 2).
Consider Novel Therapeutics Early in Disease Course: Early initiation of novel therapeutics can alter the natural course of ATTR, improving survival outcomes (Evidence: Moderate 3).References
1 Piragine E, Lucenteforte E, Veneziano S, Calderone V, Martelli A. Drugs for transthyretin amyloidosis under the microscope: Survival, safety, and a meta-analysis with certainty of evidence assessment. Pharmacological research 2025. link
2 Muller SA, Peiró-Aventin B, Biagioni G, Tini G, Saturi G, Kronberger C et al.. Evaluation of the 2021 ESC recommendations for family screening in hereditary transthyretin cardiac amyloidosis. European journal of heart failure 2024. link
3 Antonopoulos AS, Panagiotopoulos I, Kouroutzoglou A, Koutsis G, Toskas P, Lazaros G et al.. Prevalence and clinical outcomes of transthyretin amyloidosis: a systematic review and meta-analysis. European journal of heart failure 2022. link
4 Gajdusek DC. Transthyretin amyloidoses of familial amyloidotic polyneuropathy as a paradigm for the genetic control of spontaneous generation of infectious amyloids by patterned configurational change in host precursors in Creutzfeldt-Jacob disease. Acta medica portuguesa 1991. link