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cardio.acute-hf.amyloidosis.v1PRODUCTION
cardio.acute-hf.amyloidosis.v1

ADHF in cardiac amyloidosis (ATTR-CM and AL)

cardiologyacuteadult
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11/12 authored

Canonical 12-phase frame with authored status for this dossier.

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Detailed

Cardiac amyloidosis presenting as ADHF; phenotype-first triage (AL = oncologic emergency vs ATTR = disease-modifying therapy)

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Advance rule
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amyloid clinically suspected

Patient inputs (12)

MANDATORY before PYP read — rule out AL amyloidosis; difference >18 mg/L abnormal (Mayo AL staging)

Detect monoclonal protein for AL workup (combined sensitivity ~99% with SFLC)

TTR PYP scan: visual grade 2–3 + H/CL ratio ≥1.5 + negative monoclonal screen → ATTR diagnosis (no biopsy needed); otherwise endomyocardial biopsy with mass spec for definitive typing

ATTRwt overwhelmingly age >65; AL across ages; ATTRv often presents 30–60 with hereditary mutation

Cardiorenal common; tafamidis dose unaffected; patisiran requires baseline LFT/eGFR

Markedly elevated in amyloid (often >3000 even with normal LVEF); also a Mayo AL staging variable (>1800)

Persistently elevated in amyloid (myocardial infiltration); Mayo AL stage variable (cTnT >0.025 or hsTnT >40)

Apical sparing pattern (preserved apical longitudinal strain with reduced basal strain) — amyloid signature; LV wall thickness + restrictive filling

Hypotension highly common in amyloid (autonomic + restrictive); narrow tolerance for diuretics + vasodilators

Distinguish ATTRwt vs ATTRv after ATTR diagnosis confirmed (drives family screening)

V122I ATTR variant prevalent in West African / African-American descent (~3–4%) — drives variant ATTR screen

ATTRv signal — autonomic + peripheral neuropathy + bilateral carpal tunnel

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Severity triggers (5)

5 need judgement
  • informationallife_threateningal_amyloidosis_with_cardiac_stage_iii_or_iv
    AL amyloidosis (positive monoclonal screen) + Mayo cardiac stage IIIa/IIIb/IV (NT-proBNP + troponin elevated + dFLC abnormal) — oncologic emergency
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningamyloid_with_high_grade_av_block
    Mobitz II / 2:1 AV block / complete heart block in amyloid (infiltrative conduction disease) ± syncope
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereattr_cm_diagnosed_initiate_tafamidis
    ATTR-CM diagnosed via PYP (visual grade 2–3 + H/CL ≥1.5) with negative monoclonal screen — start tafamidis 61 mg daily lifelong
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereamyloid_with_diuretic_precipitated_hypotension
    Symptomatic hypotension or syncope after diuretic dose increase in amyloid (restrictive physiology preload-dependent)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveredigoxin_inadvertently_prescribed_in_amyloid
    Digoxin prescribed in cardiac amyloidosis (frequently transferred patients with prior AF treatment)
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

Cardiac amyloidosis ADHF — AL vs ATTR phenotype-based regimen (ESC 2023 PMID 37596926)
axis: cardiac_amyloidosis_phenotype_based
Selected axis "Cardiac amyloidosis ADHF — AL vs ATTR phenotype-based regimen (ESC 2023 PMID 37596926)" by default fallback (first axis)
  • tafamidis
    first line
    ttr_stabilizer
    61 mg PO daily (free acid; equivalent to tafamidis meglumine 80 mg) • PO • daily lifelong
    triggers: attr_cm_diagnosed, nyha_class_1_or_2_attr
    ATTR-ACT (Maurer NEJM 2018; PMID 30145930) — 30% all-cause mortality reduction over 30 mo; greatest benefit NYHA I–II; less impact NYHA III
    rxcui 1545063
  • patisiran
    add on
    ttr_silencer_sirna
    0.3 mg/kg IV every 3 weeks (premedicate with dex/H1/H2/acetaminophen) • IV • every 3 weeks
    triggers: attrv_cm_with_polyneuropathy, attr_cm_progression_on_tafamidis
    APOLLO (Adams NEJM 2018; PMID 30144829) — siRNA reduces hepatic TTR production
    rxcui 2053490
  • vutrisiran
    add on
    ttr_silencer_sirna
    25 mg SC every 3 months • SC • every 3 months
    triggers: attr_cm_with_polyneuropathy, tafamidis_inadequate_response
    HELIOS-A (Adams Lancet Neurol 2023; PMID 35262029) — SC dosing convenience
    rxcui 2604578
  • daratumumab
    first line
    anti_cd38_monoclonal_antibody
    1800 mg SC weekly × 8, then biweekly × 16, then monthly (with dex + bortezomib + cyclophosphamide — D-VCd regimen) • SC • per ANDROMEDA schedule
    triggers: al_amyloidosis_newly_diagnosed, al_amyloidosis_with_cardiac_involvement_stage_2_or_3a
    ANDROMEDA (Kastritis NEJM 2021; PMID 34077641) — daratumumab + CyBorD improved hematologic CR + organ response in AL
    rxcui 1721947
  • bortezomib
    first line
    proteasome_inhibitor
    1.3 mg/m² SC weekly (with cyclophosphamide + dexamethasone — CyBorD) • SC • weekly cycles per oncology
    triggers: al_amyloidosis_newly_diagnosed
    CyBorD backbone for AL (proteasome inhibition kills plasma cells); base regimen prior to ANDROMEDA daratumumab era
    rxcui 402244
  • furosemide
    first line
    loop_diuretic
    20–40 mg IV/PO (gentle — narrow preload window in restrictive physiology) • IV/PO • daily
    triggers: volume_overload_in_amyloid
    Restrictive amyloid is preload-dependent; over-diuresis precipitates hypotension/syncope; titrate carefully
    rxcui 4603
  • midodrine
    add on
    alpha1_agonist_orthostasis
    5–10 mg PO TID (last dose before 6 PM to avoid supine HTN) • PO • TID
    triggers: symptomatic_orthostatic_hypotension_amyloid_autonomic_neuropathy
    Amyloid autonomic neuropathy → orthostasis; midodrine increases vascular tone without bradycardia
    rxcui 6963

outpatient playbook — drug actions (3)

  1. 1. continue tafamidis lifelong if ATTR
    rxcui 1495093
    61 mg PO daily • PO • daily
    trigger: ATTR maintenance
    ATTR-ACT PMID 30145930 (continued benefit at 5 yr per OL extension)
  2. 2. consider gene-silencer if ATTR progression
    vutrisiran 25 mg SC q 3 mo • SC • q 3 mo
    trigger: ATTR-CM progression on tafamidis or polyneuropathy phenotype
    HELIOS-A PMID 35262029
  3. 3. continue AL maintenance per hematology
    daratumumab maintenance per ANDROMEDA • SC • monthly
    trigger: AL maintenance
    ANDROMEDA PMID 34077641

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: HF symptoms + LV wall thickness ≥12 mm + no long-standing HTN → amyloidosis screen; HF + low-voltage QRS on ECG + thick LV walls (voltage-mass mismatch — amyloid signature); Elderly male with bilateral carpal tunnel release history + new HF (ATTRwt clue).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**ADHF in cardiac amyloidosis (ATTR-CM and AL)** (cardio.acute-hf.amyloidosis.v1).
Phenotype framing: AL vs ATTRwt vs ATTRv; consider mimics (HOCM, hypertensive heart, Fabry, sarcoidosis)
Scope: Cardiac amyloidosis presenting as ADHF; phenotype-first triage (AL = oncologic emergency vs ATTR = disease-modifying therapy)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Cardiac amyloidosis ADHF — AL vs ATTR phenotype-based regimen (ESC 2023 PMID 37596926)**.
1. tafamidis 61 mg PO daily (free acid; equivalent to tafamidis meglumine 80 mg) PO daily lifelong (ttr_stabilizer, first line) — ATTR-ACT (Maurer NEJM 2018; PMID 30145930) — 30% all-cause mortality reduction over 30 mo; greatest benefit NYHA I–II; less impact NYHA III
2. patisiran 0.3 mg/kg IV every 3 weeks (premedicate with dex/H1/H2/acetaminophen) IV every 3 weeks (ttr_silencer_sirna, add on) — APOLLO (Adams NEJM 2018; PMID 30144829) — siRNA reduces hepatic TTR production
3. vutrisiran 25 mg SC every 3 months SC every 3 months (ttr_silencer_sirna, add on) — HELIOS-A (Adams Lancet Neurol 2023; PMID 35262029) — SC dosing convenience
4. daratumumab 1800 mg SC weekly × 8, then biweekly × 16, then monthly (with dex + bortezomib + cyclophosphamide — D-VCd regimen) SC per ANDROMEDA schedule (anti_cd38_monoclonal_antibody, first line) — ANDROMEDA (Kastritis NEJM 2021; PMID 34077641) — daratumumab + CyBorD improved hematologic CR + organ response in AL
5. bortezomib 1.3 mg/m² SC weekly (with cyclophosphamide + dexamethasone — CyBorD) SC weekly cycles per oncology (proteasome_inhibitor, first line) — CyBorD backbone for AL (proteasome inhibition kills plasma cells); base regimen prior to ANDROMEDA daratumumab era
6. furosemide 20–40 mg IV/PO (gentle — narrow preload window in restrictive physiology) IV/PO daily (loop_diuretic, first line) — Restrictive amyloid is preload-dependent; over-diuresis precipitates hypotension/syncope; titrate carefully
7. midodrine 5–10 mg PO TID (last dose before 6 PM to avoid supine HTN) PO TID (alpha1_agonist_orthostasis, add on) — Amyloid autonomic neuropathy → orthostasis; midodrine increases vascular tone without bradycardia

Setting playbook (outpatient) — Long-term amyloid program care: ATTR-NAC or Mayo AL stage progression monitoring, DMT adherence, family screening (ATTRv), conduction surveillance, advanced HF/transplant evaluation when DMT fails
8. continue tafamidis lifelong if ATTR 61 mg PO daily PO daily — ATTR maintenance (ATTR-ACT PMID 30145930 (continued benefit at 5 yr per OL extension))
9. consider gene-silencer if ATTR progression vutrisiran 25 mg SC q 3 mo SC q 3 mo — ATTR-CM progression on tafamidis or polyneuropathy phenotype (HELIOS-A PMID 35262029)
10. continue AL maintenance per hematology daratumumab maintenance per ANDROMEDA SC monthly — AL maintenance (ANDROMEDA PMID 34077641)

Non-pharmacologic actions:
- Family TTR genotype screening if ATTRv
- Advanced HF/transplant program referral when DMT inadequate
- Patient education + advance care planning

AVOID / contraindication checks:
- Digoxin_contraindicated_in_amyloid (binds amyloid fibrils → toxicity)
- Ccb_nondihydropyridine_contraindicated (verapamil/diltiazem also bind fibrils + worsen heart block)
- Ace_arb_caution_hypotension (amyloid autonomic + restrictive physiology poorly tolerates afterload reduction)
- Beta_blocker_caution (autonomic + restrictive — often poorly tolerated; stop if symptomatic)
- Patisiran_pretreatment_required (dexamethasone + H1 + H2 + acetaminophen for infusion reaction prevention)

Monitoring

Regimen monitoring:
- al serum free light chains weekly during chemo
- attr nt probnp and 6mwd at 6 months on tafamidis
- echo at 12 months on disease modifying therapy
- ecg q 3 months for conduction disease progression

Setting (outpatient) monitoring:
- Quarterly clinic + annual full restage
- Cross-link to advanced HF if NYHA III on max DMT

Monitoring phase: Daily weight, BMP, gentle diuresis; AL: monitor FLC weekly during chemotherapy; ATTR: NT-proBNP + 6MWD + echo at 6 mo on tafamidis

Disposition

Current setting: outpatient — Long-term amyloid program care: ATTR-NAC or Mayo AL stage progression monitoring, DMT adherence, family screening (ATTRv), conduction surveillance, advanced HF/transplant evaluation when DMT fails

Disposition criteria:
- Long-term amyloid program continuation; cross-link to cardio.hf.core.v1 for residual HF management; cross-link to cardio.acute-hf.core.v1 for inpatient decompensations

Escalation triggers (move to higher acuity):
- Disease progression on max DMT → advanced HF / transplant or hospice
- New conduction disease → PPM/ICD eval

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] AL amyloidosis (positive monoclonal screen) + Mayo cardiac stage IIIa/IIIb/IV (NT-proBNP + troponin elevated + dFLC abnormal) — oncologic emergency
- [LIFE_THREATENING] Mobitz II / 2:1 AV block / complete heart block in amyloid (infiltrative conduction disease) ± syncope
- [SEVERE] ATTR-CM diagnosed via PYP (visual grade 2–3 + H/CL ≥1.5) with negative monoclonal screen — start tafamidis 61 mg daily lifelong

Citations

- ESC 2023 cardiac amyloidosis position statement + ACC/AHA 2023 expert decision pathway (Kittleson) + ATTR-ACT + ANDROMEDA + APOLLO + HELIOS-A [PMID:37596926](https://pubmed.ncbi.nlm.nih.gov/37596926/)
- Cited evidence (PMID 30145930) [PMID:30145930](https://pubmed.ncbi.nlm.nih.gov/30145930/)
- Cited evidence (PMID 34077641) [PMID:34077641](https://pubmed.ncbi.nlm.nih.gov/34077641/)
- Cited evidence (PMID 30144829) [PMID:30144829](https://pubmed.ncbi.nlm.nih.gov/30144829/)
- Cited evidence (PMID 35262029) [PMID:35262029](https://pubmed.ncbi.nlm.nih.gov/35262029/)

Last reconciled with current guidelines: 2026-05-14.
References
  • ESC 2023 cardiac amyloidosis position statement + ACC/AHA 2023 expert decision pathway (Kittleson) + ATTR-ACT + ANDROMEDA + APOLLO + HELIOS-A — PMID:37596926
  • Cited evidence (PMID 30145930) — PMID:30145930
  • Cited evidence (PMID 34077641) — PMID:34077641
  • Cited evidence (PMID 30144829) — PMID:30144829
  • Cited evidence (PMID 35262029) — PMID:35262029