Understanding Diagnostic Gaps Among Medicare Patients with ATTRwt-CM

A recent analysis of US Medicare Fee-for-Service claims data has identified a discrepancy between diagnostic coding for wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) and the frequency of recommended diagnostic testing.

Conducted between 2018 and 2022, the study evaluated claims for 2,050 patients aged 65 years and older who had received an ATTRwt-CM diagnosis and had documented heart failure or cardiomyopathy. Researchers found that while new diagnoses of ATTRwt-CM increased nearly threefold during the study period, the majority of patients did not undergo testing consistent with current diagnostic algorithms.

Only 14% of patients received the full noninvasive diagnostic workup defined by clinical guidelines, which includes technetium-99m pyrophosphate (99mTc-PYP) scintigraphy and a comprehensive monoclonal protein screen involving serum and urine electrophoresis with immunofixation and free light chain assays. Although PYP imaging alone was used more frequently over time—rising from 30% in 2018 to 49% in 2022—complete laboratory testing remained infrequent.

A Shift Toward Noninvasive Tools

Since 2016, guidelines have supported a non-biopsy diagnosis of ATTRwt-CM in the presence of PYP cardiac uptake and absence of monoclonal gammopathy. PYP scintigraphy, when used without adequate laboratory exclusion of AL amyloidosis, has limited specificity. The current data show that by 2022, just 16% of patients underwent both PYP imaging and full monoclonal testing. In nearly 10% of cases, PYP imaging was performed without any documented monoclonal testing.

Over the same period, the use of cardiac biopsy declined from 14% in 2018 to 5% in 2022. These trends reflect broader adoption of noninvasive diagnostic methods, yet the data indicate that a substantial proportion of patients were diagnosed with ATTRwt-CM without either biopsy or full laboratory confirmation.

Diagnostic Testing Patterns and Comorbidity Burden

Patients diagnosed with ATTRwt-CM in this study had a median age of 80 years and were predominantly male (76%) and White (78%). Cardiovascular comorbidities were prevalent, including hypertensive disease (77%), heart failure (75%), cardiac arrhythmias (69%), and ischemic heart disease (61%). Non-cardiac conditions commonly associated with amyloidosis, such as chronic kidney disease (41%), pleural effusions (34%), and carpal tunnel syndrome (15%), were also frequently observed.

These clinical features are consistent with known disease manifestations. However, the findings do not clarify whether diagnostic testing was prompted by clinical suspicion of amyloidosis or by broader screening practices. Additionally, the absence of confirmatory testing in many cases limits interpretation of the diagnostic accuracy behind the assigned codes.

Administrative Data Constraints and Generalizability

This study relied on administrative claims and was limited to patients with continuous Medicare Part A, B, and D coverage. The design likely captured most reimbursed diagnostic procedures but could not assess results or clinical decision rationales. The study excluded individuals with codes or treatment suggestive of AL amyloidosis or other amyloid subtypes to minimize misclassification, but miscoding remains a known limitation of claims-based research.

Because only patients already diagnosed with ATTRwt-CM were included, the analysis does not evaluate broader testing rates among individuals with unexplained cardiomyopathy or heart failure. Results may not apply to populations outside Medicare FFS, such as those with private insurance or those under 65 years of age.

Clinical Relevance of Incomplete Evaluation

Among the 2,050 patients studied, only 44% to 54% had claims for either PYP imaging or cardiac biopsy. The study could not determine the diagnostic basis for the remaining individuals. Given the diagnostic implications of monoclonal gammopathies and the therapeutic differences between AL and ATTR types of amyloidosis, the absence of comprehensive testing may have implications for treatment selection and disease monitoring.

These findings indicate that although utilization of cardiac imaging for ATTRwt-CM increased over the study period, comprehensive application of recommended diagnostic algorithms was limited. Further investigation into barriers to full testing—including access, awareness, and documentation practices—may support improved alignment with clinical guidelines.

Implications for Practice and Data Interpretation

This analysis contributes to the understanding of diagnostic patterns for ATTRwt-CM in older adults within the Medicare system. The results suggest that while recognition of the disease is increasing, application of the full diagnostic pathway remains inconsistent. Future research may clarify whether these patterns affect therapeutic decisions, particularly given the availability of disease-specific treatments. Standardizing the use of both imaging and laboratory testing in suspected ATTR-CM cases may improve diagnostic confidence and reduce reliance on coding alone as evidence of disease presence.

Reference:
Witteles RM, Chung H, Dai F, et al. Trends in diagnostic testing in Medicare patients with wild-type transthyretin amyloid cardiomyopathy. Front Cardiovasc Med. 2025;12:1638380. doi:10.3389/fcvm.2025.1638380