Table 1.
General treatment strategies for cardiac amyloidosis subtypes. Adapted from @Springer Science + Business Media LLC, Stern and Kittleson.2 GDMT: guideline-directed medical treatment *with ace-inhibitors, angiotensin receptor blockers, angiotensin receptor blocker-neprilysin inhibitor, beta-blockers, aldosterone antagonists, sodium glucose cotransporter-2 inhibitors; AF: atrial fibrillation or atrial flutter; DOAC: direct oral anticoagulant; VKA: vitamin-K antagonist; PPM: permanent pacemaker; ICD: implantable cardioverter defibrillator; VT: ventricular tachycardia; SCD: aborted sudden cardiac death; HRS: Heart Rhythm Society; AL: light chain amyloidosis; ATTRv: hereditary transthyretin amyloidosis; ATTRwt: wild-type ATTR amyloidosis; CM: cardiomyopathy; PN: polyneuropathy; PO: per oral administration; SQ: subcutaneous administration; IV: intravenous administration; FDA: Food and Drug Administration; CyBorD: cyclophosphamide-bortezomib-dexamethasone; BMD: bortezomib-melphalan-dexamethasone; ASCT: autologous stem cell transplant
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| TREATMENT CATEGORY | TREATMENT | COMMENTS AND CAVEATS |
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| Heart failure | Loop diuretics | Favor bioavailable (bumetanide, torsemide) |
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| GDMT* if tolerated | Clinical benefit not established May be poorly tolerated due to restrictive physiology and renal dysfunction |
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| Autonomic dysfunction | (1) Midodrine (2) Droxidopa (3) Pyridostigmine (4) Compression stockings |
(1–3) Usually AL-CA and ATTRv-CA (3) Not formally studied in CA (4) For orthostasis and mobilization of peripheral edema for all types of CA |
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| Arrhythmias | ||
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| Medical | Amiodarone (AF) | Usually tolerated over nodal blocking agents due to tendency for conduction disease and heart rate dependence; no difference for rate or rhythm control |
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| Anticoagulation (AF) | DOAC or VKA Prescribed regardless of CHA2DS2-VASc score |
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| Device | PPM (Heart block) | CRT may be considered in select PPM-dependent patients |
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| ICD (VT/SCD) | Heart Rhythm Society recommendation75: Primary prevention: AL-CA with NSVT with > 1 yr life expectancy (IIb) Secondary: > 1 yr life expectancy (Ic) |
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| Advanced therapies | Heart transplant | AL-CM: select patients with good response to chemotherapy/immunotherapy and minimal extracardiac involvement ATTR-CM: Select patients with minimal extracardiac symptoms |
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| Heart-liver transplant | ATTRv-CM + PN: liver transplant may be unnecessary in the future with advances in silencer therapy | |
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| Currently available disease-modifying therapy | ||
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| ATTR-CA | ||
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| ATTRwt-CM | (1) Tafamidis (2) Diflunisal |
TTR stabilizers: halts disease progression PO tablets (1) FDA approved (2) Off-label, NSAID: contraindicated for renal failure and thrombocytopenia; used cautiously with anticoagulation and gastrointestinal bleed |
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| ATTRv-CM | (1) Tafamidis (2) Diflunisal |
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| ATTRv-CM + PN | (1) Tafamidis (2) Inotersen (3) Patisiran (4) Diflunisal |
TTR stabilizers: (1) FDA approved (4) off-label TTR silencers: prevent amyloid formation (2) SQ, risk of thrombocytopenia and glomerulonephritis (3) IV, fewer reported side effects |
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| ATTRv-PN | (1) Inotersen (2) Patisiran (3) Diflunisal |
TTR silencers (1,2) TTR stabilizer (3) off label |
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| AL-CA | ||
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| Chemotherapy | CyBorD/BMD | Most common chemotherapy regimens in patients who are not candidates for ASCT and as up-front therapy with daratumumab Corticosteroids/volume of therapy may precipitate decompensated heart failure |
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| Immunotherapy | Daratumumab | Anti-CD38 monoclonal antibody Only FDA-approved therapy for AL amyloidosis Up-front therapy combined with bortezomib-based chemotherapy regimens |
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| (1) Lenalidomide (2) Pomalidomide (3) Thalidomide |
Thalidomide analogs (1–3): Generally reserved for relapsed disease Potential cardiac and renal toxicity |
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| Transplant | High-dose melphalan + ASCT | Preferred approach but rarely offered if significant cardiac and/or other organ involvement May be performed after heart transplantation |
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