Diagnostic Gaps in ATTR-CM: Insights from a Multispecialty Survey in France

Despite increasing treatment options and growing clinical awareness, timely diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) remains an ongoing challenge.

To better understand how different specialists engage in this diagnostic process, the DIAM-ATTR survey offers a nationwide lens into real-world practice in France. Findings, published in Annals of Medicine in 2025, reflect insights from over 1,200 healthcare professionals (HCPs) across seven specialties, revealing variability in both recognition of clinical signs and execution of diagnostic workup.

Here’s a brief overview of the results.

Specialty Distribution
The DIAM-ATTR study solicited over 13,800 HCPs involved in the diagnosis of cardiac amyloidosis, with 1,264 completing the full survey. Cardiologists represented the largest group (37%), followed by internists, nuclear medicine physicians, geriatricians, orthopaedic surgeons, neurologists, and rheumatologists.

More than two-thirds (70%) of respondents had previously suspected ATTR-CM in a patient. Unsurprisingly, cardiologists led the way (96%), but internists (87%), neurologists (61%), and geriatricians (62%) also showed substantial involvement.

In contrast, only 6% of orthopaedic surgeons and 25% of rheumatologists had ever raised suspicion of the condition.

Initial Testing Patterns
Across nearly all specialties, echocardiography was the default first-line test. Among cardiologists, it was prioritized by 73% as the initial diagnostic examination, followed by assessment for monoclonal gammopathy and bone scintigraphy.

Internists, while similarly reliant on echo, more frequently pursued gammopathy workup and even biopsies earlier in the process.

Notably, many physicians performed cardiac MRI as a second-line test, even though it is not required for ATTR-CM diagnosis and introduces delays of up to four weeks.

AL Amyloidosis Oversight
While most specialists recognized the need to rule out AL amyloidosis, less than two-thirds performed the full recommended panel: serum protein electrophoresis, immunofixation, serum free light chains, and urine studies. Only 33% completed all six key tests. Cardiologists outperformed other groups on this front, but still fell short of universal adoption.

This represents a critical gap. Since bone scintigraphy results must be interpreted in the context of gammopathy exclusion, failure to fully assess for AL amyloidosis can lead to diagnostic error or delay, especially given the aggressive nature of AL-amylodosis cardiomyopathy.

Red Flag Variability
The survey also assessed clinicians’ awareness of 22 clinical “red flags” for cardiac amyloidosis. Echocardiographic abnormalities, heart failure, and family history of amyloid neuropathy were broadly acknowledged. However, signs like conduction disorders, dysautonomia, or osteoarticular involvement (e.g., carpal tunnel syndrome) were more inconsistently flagged—especially by non-cardiology specialists. Rheumatologists and orthopaedic surgeons, despite often encountering early signs like Dupuytren’s contracture or joint replacements, rarely associated these features with amyloidosis.

Diagnostic Bottlenecks
Median delays for key tests varied significantly.

• Echocardiography: 1-2 weeks for most; up to 3 for neurologists.
• Scintigraphy and biopsy: Typically 2-3 weeks; longer for neurologists.
• Cardiac MRI: Delayed across all groups (median 4-6 weeks).
• Genotyping: Extended delays of 3-6 months; particularly limiting for hereditary forms.

These delays compound when MRI is over-prioritized or referrals are delayed. Notably, 48% of cardiologists and internists completed the full diagnostic workup themselves, while other specialties largely referred out at various stages.

System-Level Needs
Despite France’s relatively advanced infrastructure for rare diseases, this study highlights ongoing needs, including:

• Expanded awareness of early musculoskeletal signs and systemic features.
• More consistent application of the full gammopathy exclusion protocol.
• Reduced dependence on MRI when not essential to diagnosis.
• Improved access to genetic testing and expert referral centers.

Practice Implications
In sum, the DIAM-ATTR survey paints a picture of partial alignment with guideline-recommended pathways for ATTR-CM diagnosis in France. While cardiologists and internists are well-positioned to lead the diagnostic process, knowledge and access gaps remain—especially among specialties more likely to encounter patients with early extracardiac manifestations.

A multidisciplinary, networked approach remains essential to close these diagnostic delays and optimize outcomes for patients with cardiac amyloidosis.

Reference:
Oghina S, Legallois D, Hyafil F, et al. Diagnostic pathway for cardiac amyloidosis from the healthcare professional’s perspective: results from the French DIAM-ATTR survey. Ann Med. 2025;57(1):2525391. doi:10.1080/07853890.2025.2525391