In morning report this week, we discussed a case of a patient presenting with new heart failure with findings of restrictive cardiomyopathy that we found out later was due to cardiac amyloidosis.
Below are some key learning points that we discussed.
- Diagnostic Approach to Heart Failure with Preserved Ejection Fraction
- DDx of HFpEF includes:
- HTN
- Valvular disease
- Infiltrative diseases (Amyloid, Hemochromatosis, sarcoidosis, Glycogen storage diseases)
- CAD
- Hypertrophic cardiomyopathy
- Pericardial disease (constrictive pericarditis)
- Other causes of restrictive CM: e.g., carcinoid, scleroderma, endomyocardial fibrosis (e.g. secondary to hypereosinophilia or drugs), radiation, chemo, cancer

Approach to Restrictive Cardiomyopathy

Types of Amyloidosis
- Systemic Amyloidosis/ Light chain (AL) Amyloidosis: most common
- Transthyretin (TTR) Amyloidosis
- Serum Amyloid A (AA) = Secondary
- Caused by chronic inflammation such as infection (TB), inflammation (untrreated RA); rarely cardiac
- Aβ2MG amyloidosis (Hemodialysis associated amyloidosis)

Signs and Symptoms of Amyloidosis
- Amyloid is systemic! Involving multiple organs.
- Extra cardiac manifestations:
- Kidneys (proteinuria, renal failure)
- Liver (Elevated ALP, hepatic failure)
- GI tract (Dysphagia, constipation, malabsorption, GI bleeding)
- HEENT: Macroglossia, may have OSA, carpal tunnel syndrome, voice/nail changes
- Nerves (peripheral neuropathy, autonomic dysfunction)
- MSK: Shoulder pad sign
- Cardiac dysfunction:
- HFpEF >>HFrEF
- Conduction disease with heart block, tachyarrhythmias and low voltage on ECG
- LVH and LV mass on TTE
- Elevated BNP, elevated troponin (destruction cardiomyocytes)
- Combination of increased LV mass & low voltage is very specific for amyloid!
Investigations
- CBC, lytes, creatinine, urinalysis/ACR/24 hour urine, liver function tests
- SPEP, serum immunofixation and free light chain assay
- BNP, troponin, ECG –> In AL cardiac amyloidosis, staging is based on troponin and BNP
- Echocardiogram +/- cardiac MRI
- Biopsy is gold standard: bone marrow biopsy +/- cardiac or noncardiac biopsy
- E.g., Fat pad biopsy (AL amyloid; sensitivity of ~70%) or Endomesial biopsy (gold standard, most invasive)
- If no plasma cell dyscrasia, may do nuclear update assessment and then consider genetic testing for TTR mutation



Management of AL Cardiac Amyloidosis
- Goal: 1) Treat consequences of organ dysfunction
2) Slow progression- target clonal plasma cells - Cardiac (BNP, troponin) and hematologic parameters are prognostic
CHF treatment
- Avoid BB/CCB/Digoxin
- Intolerance of ACE inhibitors
- Spironolactone
- Salt restriction
- Midodrine
- Consider heart transplant/LVAD, CRT-D
Chemotherapy for AL Amyloidosis
- Most common regimen is CyBorD = bortezomib with cyclophophadmide, dexamethasone
- In one study, only 17% with cardiac involvement responded
- Rarely, stem cell transplant may be considered
- ATTR amyloid treated differently
Further Reading: