Rare Disease AdvisorSymptoms of Heart Failure Should Prompt Suspicion of ATTR-CM

ℹ️ Observational Association Only Evidence

ATTR-CM is frequently underdiagnosed in older adults with heart failure, in part because its symptoms and comorbidities overlap with more common HF etiologies. This retrospective cohort of 7,770 Medicare beneficiaries (2016-2022) characterized diagnostic delay patterns and identified clinical features associated with earlier or later ATTR-CM recognition.

Clinical Considerations

• Median time from heart failure diagnosis to ATTR-CM diagnosis was 494 days; among the 79.5% prescribed a loop diuretic pre-diagnosis, the median delay extended to 840 days
• Older age, atrial fibrillation, and carpal tunnel syndrome were associated with a reduced likelihood of delayed diagnosis, suggesting these features prompt earlier ATTR-CM suspicion
• Female sex, aortic stenosis, COPD, CAD, diabetes, and hypertension were associated with greater diagnostic delay, likely because these conditions provide alternative explanations for HF symptoms
• Median age at ATTR-CM diagnosis was 81 years; 77% of patients were male, consistent with known epidemiology but limiting generalizability to women
• Study design does not establish causality and cannot account for variation in clinician awareness of ATTR-CM across the study period

Practice Applications

• Recognize ATTR-CM as a diagnostic consideration in older patients with HF, particularly when loop diuretic dependence is established without a clear etiology
• Interpret carpal tunnel syndrome and atrial fibrillation as clinical features warranting earlier ATTR-CM workup in the appropriate HF context
• Avoid anchoring to common HF comorbidities (CAD, hypertension, diabetes) as sufficient explanation when symptom burden or disease trajectory suggests an alternative etiology
• Consider ATTR-CM evaluation in women with HF, where diagnostic delay appears more pronounced