Overview
This lecture discusses the identification, diagnosis, and management of cardiac amyloidosis, emphasizing clinical suspicion, diagnostic algorithms, and recent advances in therapy.
Introduction to Cardiac Amyloidosis
- Cardiac amyloidosis occurs when misfolded proteins (AL or TTR) deposit in the heart, causing restrictive cardiomyopathy.
- Two main types: AL (light-chain) from plasma cell disorders, and ATTR (transthyretin), either wild-type (age-related) or variant (genetic mutation).
Clinical Suspicion and Presentation
- Suspect amyloidosis in heart failure with preserved ejection fraction (HFpEF) and unexplained left ventricular wall thickening.
- Look for clues: no hypertension, elevated troponin with normal coronaries, carpal tunnel syndrome (especially bilateral/older age), lumbar spinal stenosis, biceps tendon rupture, or neuropathy.
- Autonomic dysfunction (orthostatic hypotension) and intolerance to vasodilators are red flags.
Diagnosis: Workup and Algorithms
- EKG may show low or discordant voltage, but normal voltage does not rule out amyloidosis.
- Begin with monoclonal protein screening: serum and urine immunofixation electrophoresis and free light chain assays.
- If positive for monoclonal protein, refer to hematology and pursue tissue biopsy for AL amyloidosis.
- If negative for monoclonal protein, order Technetium-99m pyrophosphate (PYP) scan; a positive scan supports ATTR diagnosis.
- Genetic testing distinguishes ATTR wild-type from variant forms.
- Cardiac MRI is not required for diagnosis unless the differential is unclear.
Management and Treatment
- AL amyloidosis: treat with hematology-directed chemotherapy; cardiology manages symptoms.
- ATTR amyloidosis: Tafamidis is the FDA-approved TTR stabilizer, shown to reduce mortality and hospitalizations.
- Silencer therapies (e.g., patisiran) are approved for variant ATTR with neuropathy but not for cardiomyopathy alone.
- Guideline-directed heart failure medications (e.g., ACEi, ARB, beta-blockers) are often poorly tolerated; prioritize symptom management.
- Patients with amyloidosis and atrial fibrillation require anticoagulation regardless of CHADS-VASc score.
Key Terms & Definitions
- Amyloidosis — Condition where misfolded proteins deposit in organs causing dysfunction.
- AL (light-chain) amyloidosis — Amyloidosis from plasma cell disorders producing abnormal light chains.
- ATTR amyloidosis — Amyloidosis from transthyretin protein, either wild-type or variant (genetic).
- Technetium-99m pyrophosphate scan — Nuclear imaging test to detect ATTR cardiac amyloid.
- Tafamidis — Medication that stabilizes TTR tetramers, slowing ATTR amyloidosis progression.
Action Items / Next Steps
- Review clinical features that should prompt suspicion of cardiac amyloidosis.
- Practice ordering and interpreting the correct amyloidosis diagnostic tests.
- Read about tafamidis and other therapies for ATTR amyloidosis.
- Know when to refer to cardiology or hematology specialists.