December 17, 2025Journal of the American College of Cardiology
Delayed Diagnosis of Transthyretin Amyloid Cardiomyopathy in the Veterans Health Administration
Key result
Comorbid CKD is linked to ~79% higher odds of delayed ATTR-CM diagnosis.
- n=2,557
Why the study?
Timely diagnosis and treatment of transthyretin amyloidosis with cardiomyopathy (ATTR-CM) are critical, but there is limited data on delays and predictors of diagnosis in clinical practice.
Study Design
Type
Cohort (n=2,557)
Multicenter
Yes
Structured PICO
P
Population
2,557 veterans (mean age 81 years, 99.5% male) with heart failure and ATTR-CM diagnosed between 2016 and 2022.
O
Outcome
Time to diagnosis of ATTR-CM, defined as the number of days between each patient's first HF diagnosis and their first ATTR-CM diagnosis
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“These findings uncover an opportunity for clinicians to consider concomitant ATTR-CM in patients with alternate etiologies for their cardiomyopathy, as expediting evaluation for ATTR-CM following [heart failure] diagnosis is critical to reduce the morbidity of this progressive condition.”
HMHarlan M. KrumholzEditor-in-Chief, JACC; Professor of Medicine, Yale
“This is not a failure of individual clinical acumen. It is the predictable result of asking humans to synthesize fragmented signals across years of care without systematic support. We celebrate the astute clinician who makes a difficult diagnosis, but rarely ask how many people never encounter that clinician, or arrive too late for insight to matter. That approach cannot meet the needs of a prevalent treatable disease. It is neither scalable nor equitable.”
Implication
There is a clinically important delay of median 490 days between incident heart failure and ATTR-CM diagnosis, which is further prolonged in patients with concomitant atrial fibrillation, coronary artery disease, or chronic kidney disease.
Abstract
BACKGROUND Timely diagnosis and treatment are critical to reduce morbidity and mortality for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Limited existing data suggest underdiagnosis of ATTR-CM and inequity in predictors of diagnosis patterns. OBJECTIVE This study sought to describe the time from heart failure (HF) diagnosis to ATTR-CM diagnosis and identify predictors for delayed diagnosis of ATTR-CM. METHODS This retrospective cohort study used Veterans Health Administration (VHA) data. We identified patients with HF and ATTR-CM diagnosed between 2016 and 2022 using an algorithm based on diagnoses and medications. The primary outcome was the time to diagnosis of ATTR-CM and was defined as the number of days between each patient's first HF diagnosis and their first ATTR-CM diagnosis. We also evaluated the number of days between first HF hospitalization or first loop diuretic prescription and ATTR-CM diagnosis. We used multivariable logistic regression to assess demographic, clinical, and socioeconomic predictors of time to ATTR-CM diagnosis using >6 months as a meaningful delay. RESULTS A total of 2,557 patients with HF and ATTR-CM were identified. The mean age at the time of ATTR-CM diagnosis was 81 years. Most veterans were male (2,544; 99.5%) and White (1,440; 56%). The median time to diagnosis to ATTR-CM was 490 days. For the 1,882 veterans with a loop diuretic prescription before ATTR-CM diagnosis, the median time between initial loop prescription and ATTR-CM diagnosis was 835 days (Q1-Q3: 250-1850). Across Department of Veterans Affairs sites, the median number of days to diagnosis ranged from 169 to 1,070 days. After adjustment, Black race (OR: 0.71; 95% CI: 0.57-0.88) and older age (OR: 0.66; 95% CI: 0.59-0.73) were associated with a shorter time to diagnosis, whereas a history of atrial fibrillation (OR: 1.21; 95% CI: 1.00-1.45), coronary artery disease (OR: 1.38; 95% CI: 1.15-1.64), or chronic kidney disease (OR: 1.79; 95% CI: 1.50-2.15) was associated with longer time to diagnosis. CONCLUSIONS There are clinically important delays between incident HF and diagnosis of ATTR-CM. Carrying a diagnosis of atrial fibrillation, coronary artery disease, or chronic kidney disease was associated with a longer delay to diagnosis. These findings uncover an opportunity for clinicians to consider concomitant ATTR-CM in patients with alternate etiologies for their cardiomyopathy, as expediting evaluation for ATTR-CM following HF diagnosis is critical to reduce the morbidity of this progressive condition.
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Cite This Study
Spencer‐Bonilla et al. (2025) conducted a cohort in Heart failure and transthyretin amyloidosis with cardiomyopathy (ATTR-CM) (n=2,557). Clinical comorbidities (atrial fibrillation, coronary artery disease, chronic kidney disease) vs. Patients without these comorbidities was evaluated on Time to diagnosis of ATTR-CM (days between first HF diagnosis and first ATTR-CM diagnosis). Comorbid chronic kidney disease (OR 1.79), coronary artery disease (OR 1.38), and atrial fibrillation (OR 1.21) were associated with longer delays in ATTR-CM diagnosis (overall median 490 days).