Related Experiment Video
Updated: Aug 6, 2026
Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
Delayed Diagnosis of Transthyretin Cardiac Amyloidosis Is Associated With Heart Failure Hospitalizations and
Gabriela Spencer-Bonilla1, Jun Fan2, Anubodh Sunny Varshney1
1Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA.
Insights
Diagnostic delays in transthyretin cardiac amyloidosis (ATTR-CM) are linked to worse outcomes. Longer time from heart failure (HF) diagnosis to ATTR-CM diagnosis increases risks of hospitalization and death.
Area of Science:
- Cardiology
- Amyloidosis Research
- Health Services Research
Background:
- Transthyretin cardiac amyloidosis (ATTR-CM) is an underdiagnosed cause of heart failure (HF).
- Diagnostic delays in ATTR-CM may worsen cardiac injury, but outcome associations are unclear.
Purpose of the Study:
- To assess time from HF diagnosis to ATTR-CM diagnosis as a marker of disease progression.
- To evaluate the association between diagnostic delay and heart failure hospitalization (HFH) or mortality.
Main Methods:
- Retrospective cohort study using Medicare and Veterans Health Administration (VHA) data (2016-2022).
- Identified patients with ATTR-CM using a validated algorithm.
- Analyzed time-to-diagnosis (HF diagnosis to ATTR-CM diagnosis) and its association with death or HFH using Cox models.
Main Results:
- 7,770 Medicare beneficiaries and 2,557 VHA patients with HF and ATTR-CM were identified.
- Median time-to-diagnosis was approximately 490 days in both cohorts.
- Each 1-year delay in diagnosis was associated with a 7% increased risk of death or HFH in both Medicare (HR: 1.07) and VHA (HR: 1.07) cohorts.
Conclusions:
- Diagnostic delay in ATTR-CM is a significant indicator of disease progression.
- Longer delays correlate with increased risk of heart failure hospitalization and mortality across real-world populations.
Background:
Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive, underdiagnosed cause of heart failure (HF). Diagnostic delays may increase cardiac injury at treatment initiation, but the relationship between delay and outcomes remains poorly defined.
Objectives:
The purpose of this study was to evaluate time from HF diagnosis to ATTR-CM diagnosis as a proxy for disease progression and its association with HF hospitalization (HFH) and mortality.
Methods:
This retrospective cohort study used Medicare fee-for-service and Veterans Health Administration (VHA) data. We identified patients diagnosed with ATTR-CM between 2016 and 2022 using a validated algorithm based on diagnoses and medications. Time-to-diagnosis was defined as days between each patient's first HF diagnosis and first amyloid diagnosis. Using multivariable Cox models, we evaluated its association with death or HFH.
Results:
We identified 7,770 Medicare beneficiaries and 2,557 Veterans with HF and ATTR-CM. Median age at diagnosis was 81 years in both cohorts (Medicare IQR: 76-86; VHA IQR: 74-87); women comprised 1,775 (22.8%) of Medicare and 13 (0.5%) of VHA patients. Median time-to-diagnosis was 494 days (IQR: 63-1,340) for Medicare and 490 days (IQR: 69-1,286) for VHA. After adjustment for sociodemographics, each 1-year delay was associated with a 7% increased risk of the primary outcome (Medicare HR: 1.07; 95% CI: 1.06-1.08; VHA HR: 1.07; 95% CI: 1.05-1.09). Results were similar after adjusting for comorbidities.
Conclusions:
Across 2 real-world populations, diagnostic delay in ATTR-CM is a clinically meaningful marker of disease progression, with longer delays associated with increased HFH and mortality.
Related Concept Videos
01:27Heart Failure I: Introduction
01:30Heart Failure IV: Classification and Diagnostic Evaluation
01:30Cardiomyopathy II: Dilated Cardiomyopathy
01:17Pathophysiology of Heart Failure
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:30Acute Coronary Syndrome III: Diagnostic Studies