Advancing Diagnosis of Transthyretin Cardiac Amyloidosis in Underserved Populations

A new study out of Cape Fear Valley Medical Center in North Carolina presents a community-based model for identifying transthyretin cardiac amyloidosis in high-risk populations often left behind by traditional referral pathways. The research, which explores both the feasibility and impact of structured screening in medically underserved areas (MUAs), sheds light on both persistent barriers and promise in diagnosing this underrecognized condition.

A Hidden Diagnosis in Vulnerable Populations

This study focused on a cohort of 37 patients across rural and nonrural MUAs who underwent technetium-99m pyrophosphate (99mTc-PYP) scintigraphy between 2021 and 2024. Approximately two-thirds of the cohort identified as African American. Notably, nearly 30% of these patients showed positive scans consistent with transthyretin cardiac amyloidosis despite prior misdiagnoses, such as hypertensive heart disease in several cases.

These findings highlight how transthyretin cardiac amyloidosis is underdiagnosed in MUAs, where advanced heart failure (AHF) centers and cardiac biopsy services are frequently limited.

High-Value, Low-Resource Diagnostics

While 99mTc-PYP imaging is considered a gold standard for noninvasive ATTR-CA detection, its implementation in community settings has been questioned. However, Cape Fear Valley Hospital demonstrated successful deployment using standardized imaging protocols—planar and SPECT imaging—interpreted via heart-to-contralateral lung uptake ratios.

Some key criteria for selecting patients included:

• Age >60 with heart failure
• Diastolic dysfunction and increased LV wall thickness
• Conduction system abnormalities or atrial arrhythmias
• Elevated troponin or NT-proBNP levels

All patients were screened to exclude light chain amyloidosis before PYP imaging.

Despite similarities in echocardiographic features between positive and negative patients, positive cases had significantly higher troponin levels and lower ECG voltages. Bilateral carpal tunnel syndrome emerged as a notable clinical differentiator—present in 55% of ATTR-CA positive patients vs. 8% in the negative group (p = 0.002).

Systemic Barriers and Delays

Importantly, the average time from initial heart failure diagnosis to suspicion of cardiac amyloidosis was 56 months. Contributing factors included:

• Limited access to serum/urine monoclonal protein testing
• PYP radiotracer shortages
• Low provider awareness
• Patient no-shows for outpatient testing

Patients lived an average of about 82 miles from the nearest AHF center, amplifying access challenges. The study reinforces the importance of empowering local institutions to adopt risk-based diagnostic strategies, especially where specialist infrastructure is lacking.

Beyond Diagnosis: Why Early Detection Still Matters

Even in the face of limited therapeutic access, the rationale for early diagnosis remains strong. Accurate identification alters medical management significantly. Standard heart failure drugs, such as ACE inhibitors, are often poorly tolerated and beta blockers may worsen outcomes in these patients, while others like mineralocorticoid receptor antagonists and diuretics are generally better tolerated. Additionally, early diagnosis enables timely initiation of therapy when available, facilitates clinical trial enrollment, and supports family screening in cases with hereditary patterns.

Looking Forward

Despite its retrospective design, small sample size, and lack of formal cost-analysis, this study suggests that targeted, risk-based screening for transthyretin cardiac amyloidosis using 99mTc-PYP scintigraphy may be implemented in community hospitals serving MUAs, without increasing overall health care costs. By focusing testing on patients with high pretest probability, this approach supports earlier identification of disease and improved treatment access in settings with limited specialty infrastructure. Scaling community-based screening models could therefore be pivotal in closing long-standing gaps in care.

Reference
Bahuva R, Mehta N, Riaz AH, et al. Screening and diagnosis of transthyretin cardiac amyloidosis in medically underserved populations: Feasibility, challenges, and opportunities. JACC: Advances. 2025;4(9):102061. doi:10.1016/j.jacadv.2025.102061