Cardiac Amyloidosis Diagnosis Lags After Heart Failure Onset

Transthyretin cardiac amyloidosis (ATTR-CM), once considered rare, is now recognized as an important cause of heart failure (HF), particularly HF with preserved ejection fraction (HFpEF), yet it remains substantially underdiagnosed.¹ A new cohort study published in JAMA Cardiology used Medicare fee-for-service claims from January 2016 through December 2022 to quantify diagnostic delays and identify patient characteristics associated with longer time to diagnosis.

“Timely diagnosis of transthyretin cardiac amyloidosis (ATTR-CM) is critical
for early treatment to reduce morbidity and mortality, yet the timeliness of contemporary ATTR-CM diagnosis remains poorly understood,” wrote the researchers of the study.

Researchers from Stanford University and the University of California, Los Angeles, applied a previously validated claims-based algorithm (sensitivity, 84%; positive predictive value, 94%) to identify 7770 Medicare fee-for-service beneficiaries with incident HF who subsequently met claims-based criteria for ATTR-CM. The median age at ATTR-CM diagnosis was 81 years, and 77% of the cohort was male patients

Diagnostic Delays Persisted Across the Study Period

The median (IQR) time from incident HF diagnosis to ATTR-CM diagnosis was 494 days (63-1340), and nearly two-thirds of patients (64%) went at least 6 months before receiving an ATTR-CM diagnosis. Among the 6175 patients who had initiated loop diuretic therapy, the median interval between the first prescription and ATTR-CM diagnosis was 840 days (252-1768). Even when HF hospitalization was used as the starting point, the median delay remained 276 days.

Although the annual number of ATTR-CM diagnoses increased substantially—from 415 in 2016 to a peak of 1930 in 2021—the length of the diagnostic interval did not shorten over the study period, suggesting that increases in diagnosis over time were not accompanied by faster recognition after HF onset.

Predictors of Delayed Diagnosis

After adjustment for demographic and clinical factors, several common cardiovascular and systemic comorbidities were independently associated with higher odds of delayed diagnosis: aortic stenosis (OR, 1.39; 95% CI, 1.20-1.62), coronary artery disease (OR, 1.26; 95% CI, 1.13-1.40), diabetes (OR, 1.21; 95% CI, 1.07-1.37), hypertension (OR, 1.28; 95% CI, 1.13-1.45), chronic obstructive pulmonary disease (OR, 1.18; 95% CI, 1.03-1.34), liver disease (OR, 3.30; 95% CI, 2.83-3.84), and peripheral neuropathy (OR, 3.00; 95% CI, 2.10-4.27). Female sex was also associated with longer diagnostic delays (OR, 1.28; 95% CI, 1.13-1.45), consistent with prior literature suggesting ATTR-CM is underrecognized in women.

Conversely, older age (OR, 0.68; 95% CI, 0.63-0.74), atrial fibrillation (OR, 0.39; 95% CI, 0.33-0.49), and carpal tunnel syndrome (OR, 0.85; 95% CI, 0.74-0.97) were associated with earlier diagnosis. The authors note that finding atrial fibrillation and carpal tunnel syndrome may increase clinical suspicion for amyloidosis and prompt earlier evaluation. The association between Black race and delayed diagnosis was not statistically significant after adjustment.

The authors suggest diagnostic anchoring may contribute to these delays, with clinicians attributing HF symptoms to common comorbid conditions rather than considering ATTR-CM and pursuing amyloid-specific testing. A related analysis by the same research group, drawing on both this Medicare cohort and a Veterans Health Administration cohort, found that each additional year of diagnostic delay was associated with a 7% increase in the risk of HF hospitalization or death, underscoring the potential clinical consequences of delayed recognition.²

Managed Care Implications

For payers and health systems, the findings support careful evaluation for ATTR-CM when patients with HF also present with clinical features or comorbidities associated with delayed recognition, rather than assuming more common conditions fully explain their symptoms.¹ With disease-modifying therapies now available and additional agents in late-stage development, reducing the interval between HF onset and ATTR-CM diagnosis may enable earlier treatment initiation and could help reduce downstream HF-related hospitalizations and other health care utilization.

“There were substantial delays between incident HF and diagnosis of ATTR-CM found in this study,” wrote the researchers. “Female sex and having a history of aortic stenosis, coronary artery disease, diabetes, hypertension, or chronic obstructive pulmonary disease, which are each associated with cardiomyopathy and breathlessness, were associated with delayed diagnosis. These findings highlight the need for a heightened index of suspicion for ATTR-CM in patients with other possible etiologies of cardiomyopathy or HF symptoms.”

References

1. Spencer-Bonilla G, Fan J, Cheng P, et al. Timeliness of transthyretin cardiac amyloidosis diagnosis in the Medicare population. JAMA Cardiol. 2026;11(6):524-533. doi:10.1001/jamacardio.2026.0833.
2. Spencer-Bonilla G, Fan J, Varshney AS, et al. Delayed diagnosis of transthyretin cardiac amyloidosis is associated with heart failure hospitalizations and mortality. JACC Adv. 2026;5(8):103019. doi:10.1016/j.jacadv.2026.103019