ATTR-CM Diagnosis Lags by More Than a Year After HF in Medicare Population

Transthyretin cardiac amyloidosis (ATTR-CM) is no longer considered a rare disease, yet a new study confirms it remains a persistently underdiagnosed one.¹ Research published in JAMA Cardiology found that most Medicare beneficiaries with ATTR-CM experienced significant delays for a diagnosis after their initial heart failure (HF) presentation, especially among women and patients with comorbidities.

“In this cohort study of 7770 Medicare enrollees with ATTR-CM, most patients experienced a delay of longer than 6 months, and diagnostic delay did not improve over time,” wrote the researchers of the study. “Female sex, aortic stenosis, chronic obstructive pulmonary disease, coronary artery disease, diabetes, and hypertension were associated with a statistically significant higher odds of delayed diagnosis.”

A Long Wait From Symptom to Diagnosis

Using Medicare fee-for-service data from 2016 to 2022, researchers from Stanford University and the University of California, Los Angeles, analyzed 7770 beneficiaries with confirmed ATTR-CM and a prior HF diagnosis. The median (IQR) time from incident HF to ATTR-CM diagnosis was 494 (63-1340) days. When the researchers used loop diuretic prescription as a proxy for earlier symptom onset, the median delay stretched to 840 (252-1768) days, or nearly 2 and a half years.

Critically, 64% of patients received their ATTR-CM diagnosis 6 months or more after their HF diagnosis. Despite a meaningful increase in total ATTR-CM diagnoses across the study period, the diagnostic timeline itself did not improve from 2016 through 2022.

Comorbidities as Diagnostic Noise

The study identified a consistent pattern: patients with conditions that can independently cause HF symptoms—aortic stenosis, coronary artery disease, diabetes, hypertension, and chronic obstructive pulmonary disease—had significantly higher odds of delayed ATTR-CM diagnosis. The authors described this as diagnostic anchoring, whereby clinicians attribute HF symptoms to the more familiar condition and defer further investigation.

This phenomenon is well-documented in the broader ATTR-CM literature. A targeted review published in Cardiology and Therapy found misdiagnosis occurred in 34% to 57% of patients with ATTR-CM, with evaluation by multiple providers common before reaching an accurate diagnosis.²

In contrast, older age (OR, 0.68; 95% CI, 0.63-0.74), history of 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 lower odds of delayed diagnosis.¹

Female sex (OR, 1.28; 95% CI, 1.13-1.45) was independently associated with higher odds of delayed diagnosis, even after adjusting for demographic and clinical factors. Women represented only 23% of the ATTR-CM cohort, reflecting the condition's higher prevalence in older men. But the underrepresentation of women in the disease's epidemiology may itself contribute to the diagnostic gap.

The findings underscore the need for a lower threshold of suspicion for ATTR-CM, particularly in patients whose HF symptoms are not fully explained by the most obvious comorbidity. For clinicians managing older adults with HF and concurrent aortic stenosis, coronary artery disease, or hypertension, a concurrent workup for amyloidosis may reduce the risk of anchoring on a competing diagnosis.

“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,” wrote the researchers. “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. Published online April 29, 2026. doi:10.1001/jamacardio.2026.0833

2. Rozenbaum MH, Large S, Bhambri R, et al. Impact of delayed diagnosis and misdiagnosis for patients with transthyretin amyloid cardiomyopathy (ATTR-CM): a targeted literature review. Cardiol Ther. 2021;10(1):141-159. doi:10.1007/s40119-021-00219-5