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cardio.cardiogenic-shock.amyloidosis-related.v1PRODUCTION
cardio.cardiogenic-shock.amyloidosis-related.v1

Cardiogenic shock — cardiac amyloidosis (ATTR-CM and AL)

cardiologyacuteadult
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12/12 authored

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

Current phase

Frame

Detailed

Cardiac amyloidosis presenting with shock physiology — distinct from sister acute-hf-amyloidosis variant by hemodynamic compromise; phenotype-first triage (AL = oncologic emergency vs ATTR = disease-modifying therapy with months-to-benefit needing MCS bridge)

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Amyloid CS confirmed and AL vs ATTR phenotype routing initiated

Patient inputs (17)

MANDATORY before PYP read — rule out AL amyloidosis (PYP can be falsely positive in AL); 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 in amyloid; tafamidis dose unaffected; patisiran requires baseline LFT/eGFR

Pulm congestion from restrictive filling drives congestion easily; intubation may worsen restrictive low-output state

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

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

Low-voltage QRS + pseudo-infarct pattern + AV conduction abnormalities; may show pseudo-STEMI mimicking ACS

Apical sparing pattern (preserved apical longitudinal strain with reduced basal strain — cherry-on-top sign); LV wall thickness + restrictive filling + diastolic dysfunction

SCAI 2022 staging baseline; amyloid CS often hypotensive at baseline due to autonomic + restrictive physiology — narrow tolerance window

AF very common in amyloid (~70% lifetime); rate control challenging — BB and non-DHP CCB poorly tolerated / contraindicated

SCAI staging anchor + amyloid CS often has marked lactic acidosis from restrictive low-output state

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

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

ATTRv signal — autonomic + peripheral neuropathy + bilateral carpal tunnel release history

Heart transplant ± combined heart-liver (ATTRv) for selected; advanced HF team early evaluation

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (5)

5 need judgement
  • informationallife_threateningdigoxin_toxicity_iatrogenic_error_in_cardiac_amyloid
    Patient with cardiac amyloidosis inadvertently prescribed digoxin (binds amyloid fibrils → toxicity at therapeutic-range serum levels) — emergency: stop digoxin, supportive care, digibind for severe toxicity
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningiabp_resistance_refractory_amyloid_cs_needing_va_ecmo_or_impella
    Refractory amyloid CS despite NE + IABP — escalate to Impella 5.5 or VA-ECMO bridge to disease-modifying therapy onset (months) or transplant; LV unable to recover quickly without therapy onset
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningal_amyloidosis_oncologic_emergency_timing_window
    AL amyloidosis with cardiac stage III-IV (NT-proBNP >1800, troponin >0.025, dFLC >18) at presentation — oncologic emergency with median survival <6 months without urgent Dara-CyBorD; treatment must start within 48-72 h
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningventricular_arrhythmia_storm_in_amyloid_cs
    Ventricular arrhythmia storm in amyloid CS (≥3 sustained VT episodes in 24 h) — high mortality; AVOID typical AAD given QT prolongation in amyloid; consider amiodarone with QT monitoring + beta-stimulation withdrawal + EP consult
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereadvanced_heart_failure_with_transplant_decision_window
    NYHA IV amyloid CS bridged on MCS — transplant decision window 7-14 days; combined heart-liver transplant evaluation if ATTRv (liver produces 95% of TTR)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

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Recommended regimen

Amyloid CS — phenotype-directed disease-modifying therapy + CS support; MCS bridge to therapy onset (months) or transplant
axis: amyloid_cs_phenotype_directed_therapy
Selected axis "Amyloid CS — phenotype-directed disease-modifying therapy + CS support; MCS bridge to therapy onset (months) or transplant" by default fallback (first axis)
  • norepinephrine
    first line
    vasopressor_alpha
    0.05–0.5 µg/kg/min titrate MAP ≥65 • IV • continuous
    triggers: amyloid_cs_with_sbp_lt_90, restrictive_low_output_state
    SOAP-II PMID 20200382 — NE first-line vasopressor in CS; preferred over dobutamine in amyloid (typical inotropes paradoxically worse — worsen LVOT obstruction, ventricular arrhythmia, autonomic instability)
    rxcui 7512
  • phenylephrine
    second line
    vasopressor_pure_alpha
    0.5–2 µg/kg/min titrate • IV • continuous
    triggers: amyloid_cs_with_ventricular_arrhythmia, tachyarrhythmia_intolerance_to_norepinephrine
    Pure-alpha vasopressor — useful in amyloid CS when beta-stimulation precipitates arrhythmia or worsens LVOT gradient; avoids tachyarrhythmia exacerbation
    rxcui 8163
  • tafamidis
    first line
    ttr_stabilizer
    61 mg PO daily lifelong • PO • daily
    triggers: attr_cm_diagnosed, wild_type_or_variant_attr
    ATTR-ACT (Maurer NEJM 2018 PMID 30145930) — 30% mortality reduction; benefit takes 12-30 months → MCS bridge needed for shock presentation; recommended for ALL ATTR-CM with NYHA I-III
    rxcui 1545063
  • patisiran
    add on
    sirna_ttr_silencer
    0.3 mg/kg IV q3 weeks (max 30 mg) • IV • q3 weeks
    triggers: attr_v_with_polyneuropathy, attr_with_progression_on_tafamidis
    APOLLO PMID 30144829 — siRNA TTR silencer for ATTRv polyneuropathy; trial-evidence base extending to cardiac endpoints (APOLLO-B PMID 36867222)
    rxcui 2053490
  • vutrisiran
    add on
    sirna_ttr_silencer
    25 mg SC q3 months • SC • q3 months
    triggers: attr_v_or_wt_with_polyneuropathy, preferred_dosing_convenience_over_patisiran
    HELIOS-A (PMID 35262029) — SC vutrisiran q3 mo, more convenient than patisiran IV; HELIOS-B cardiac endpoint trial supportive
    rxcui 2604578
  • daratumumab
    first line
    anti_cd38_monoclonal
    1800 mg SC weekly cycles 1-2, q2w cycles 3-6, q4w after • SC • weekly to monthly
    triggers: al_amyloidosis_diagnosed, mayo_al_stage_iii_iv_oncologic_emergency
    ANDROMEDA PMID 34077641 — Dara-CyBorD vs CyBorD alone significantly improved hematologic complete response in newly diagnosed AL; first-line for AL amyloidosis per ISA 2024 consensus
    rxcui 1721947
  • bortezomib
    first line
    proteasome_inhibitor
    1.3 mg/m2 SC weekly cycles 1-2, then per protocol • SC • weekly
    triggers: al_amyloidosis_diagnosed, cybord_backbone
    CyBorD backbone for AL amyloidosis; proteasome inhibitor for plasma-cell dyscrasia; SC route preferred over IV for neuropathy reduction
    rxcui 358258
  • cyclophosphamide
    first line
    alkylating_agent
    300 mg/m2 PO weekly per CyBorD protocol • PO • weekly
    triggers: al_amyloidosis_diagnosed, cybord_backbone
    CyBorD backbone for AL amyloidosis; alkylating cytotoxic for plasma-cell dyscrasia
    rxcui 3002
  • dexamethasone
    first line
    corticosteroid
    40 mg PO weekly per CyBorD protocol (20 mg if frail) • PO • weekly
    triggers: al_amyloidosis_diagnosed, cybord_backbone
    CyBorD backbone steroid; dose-reduce in elderly / frail / cardiac stage IV
    rxcui 3264
  • furosemide
    add on
    loop_diuretic
    GENTLE 20–40 mg IV titrate slowly • IV • bolus or low-dose continuous
    triggers: amyloid_cs_with_pulm_congestion, preload_dependent_narrow_window
    CAUTION — preload-dependent restrictive physiology; gentle diuresis only if overt congestion + adequate perfusion; large-volume diuresis precipitates hypotension and AKI (ESC 2023 cardiac amyloidosis statement PMID 37596926)
    rxcui 4603
  • midodrine
    add on
    alpha_agonist_oral
    5 mg PO TID titrate to 10 mg TID • PO • TID
    triggers: amyloid_with_orthostasis, autonomic_dysfunction_post_pressor_wean
    Oral alpha-agonist for amyloid orthostasis (autonomic dysfunction); bridge during pressor wean post-CS recovery
    rxcui 6963

outpatient playbook — drug actions (4)

  1. 1. lifelong tafamidis if ATTR
    rxcui 1163019
    61 mg PO daily • PO • daily
    trigger: ATTR-CM diagnosed
    ATTR-ACT — lifelong therapy; benefit 12-30 mo
  2. 2. gene silencer addition if progression on tafamidis
    vutrisiran 25 mg SC q3 mo (or patisiran 0.3 mg/kg IV q3w) • SC/IV • q3 mo or q3 weeks
    trigger: Progression on tafamidis or polyneuropathy component
    HELIOS-A + APOLLO — gene silencers add benefit beyond stabilizer alone
  3. 3. Dara-CyBorD until hematologic CR for AL
    per protocol with q4w maintenance • SC • weekly to monthly
    trigger: AL amyloidosis active
    ANDROMEDA — continue until durable CR
  4. 4. autologous SCT for selected AL
    high-dose melphalan + autologous stem cell rescue • IV • one-time conditioning
    trigger: Mayo Stage I-II AL without high-risk features + age <70 + good performance status
    Selected AL patients benefit from HSCT consolidation

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Cardiogenic shock + LV wall thickness ≥12 mm + no long-standing HTN → cardiac amyloidosis with shock physiology; Cardiogenic shock + low-voltage QRS on ECG + thick LV walls (voltage-mass mismatch — pathognomonic amyloid signature); Known cardiac amyloidosis (ATTR or AL) decompensating from chronic HF to shock physiology (SBP <90, lactate ≥2).

Objective

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

Assessment

**Cardiogenic shock — cardiac amyloidosis (ATTR-CM and AL)** (cardio.cardiogenic-shock.amyloidosis-related.v1).
Phenotype framing: AL vs ATTRwt vs ATTRv; consider mimics (HOCM, hypertensive heart, Fabry, sarcoidosis, hemochromatosis); rule out concurrent ACS (pseudo-STEMI ECG mimic)
Scope: Cardiac amyloidosis presenting with shock physiology — distinct from sister acute-hf-amyloidosis variant by hemodynamic compromise; phenotype-first triage (AL = oncologic emergency vs ATTR = disease-modifying therapy with months-to-benefit needing MCS bridge)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Amyloid CS — phenotype-directed disease-modifying therapy + CS support; MCS bridge to therapy onset (months) or transplant**.
1. norepinephrine 0.05–0.5 µg/kg/min titrate MAP ≥65 IV continuous (vasopressor_alpha, first line) — SOAP-II PMID 20200382 — NE first-line vasopressor in CS; preferred over dobutamine in amyloid (typical inotropes paradoxically worse — worsen LVOT obstruction, ventricular arrhythmia, autonomic instability)
2. phenylephrine 0.5–2 µg/kg/min titrate IV continuous (vasopressor_pure_alpha, second line) — Pure-alpha vasopressor — useful in amyloid CS when beta-stimulation precipitates arrhythmia or worsens LVOT gradient; avoids tachyarrhythmia exacerbation
3. tafamidis 61 mg PO daily lifelong PO daily (ttr_stabilizer, first line) — ATTR-ACT (Maurer NEJM 2018 PMID 30145930) — 30% mortality reduction; benefit takes 12-30 months → MCS bridge needed for shock presentation; recommended for ALL ATTR-CM with NYHA I-III
4. patisiran 0.3 mg/kg IV q3 weeks (max 30 mg) IV q3 weeks (sirna_ttr_silencer, add on) — APOLLO PMID 30144829 — siRNA TTR silencer for ATTRv polyneuropathy; trial-evidence base extending to cardiac endpoints (APOLLO-B PMID 36867222)
5. vutrisiran 25 mg SC q3 months SC q3 months (sirna_ttr_silencer, add on) — HELIOS-A (PMID 35262029) — SC vutrisiran q3 mo, more convenient than patisiran IV; HELIOS-B cardiac endpoint trial supportive
6. daratumumab 1800 mg SC weekly cycles 1-2, q2w cycles 3-6, q4w after SC weekly to monthly (anti_cd38_monoclonal, first line) — ANDROMEDA PMID 34077641 — Dara-CyBorD vs CyBorD alone significantly improved hematologic complete response in newly diagnosed AL; first-line for AL amyloidosis per ISA 2024 consensus
7. bortezomib 1.3 mg/m2 SC weekly cycles 1-2, then per protocol SC weekly (proteasome_inhibitor, first line) — CyBorD backbone for AL amyloidosis; proteasome inhibitor for plasma-cell dyscrasia; SC route preferred over IV for neuropathy reduction
8. cyclophosphamide 300 mg/m2 PO weekly per CyBorD protocol PO weekly (alkylating_agent, first line) — CyBorD backbone for AL amyloidosis; alkylating cytotoxic for plasma-cell dyscrasia
9. dexamethasone 40 mg PO weekly per CyBorD protocol (20 mg if frail) PO weekly (corticosteroid, first line) — CyBorD backbone steroid; dose-reduce in elderly / frail / cardiac stage IV
10. furosemide GENTLE 20–40 mg IV titrate slowly IV bolus or low-dose continuous (loop_diuretic, add on) — CAUTION — preload-dependent restrictive physiology; gentle diuresis only if overt congestion + adequate perfusion; large-volume diuresis precipitates hypotension and AKI (ESC 2023 cardiac amyloidosis statement PMID 37596926)
11. midodrine 5 mg PO TID titrate to 10 mg TID PO TID (alpha_agonist_oral, add on) — Oral alpha-agonist for amyloid orthostasis (autonomic dysfunction); bridge during pressor wean post-CS recovery

Setting playbook (outpatient) — Quarterly cardio-amyloid center surveillance: NT-proBNP + 6MWD + echo + free light chains (AL) trends; tafamidis benefit assessment at 12-30 mo; ATTRv family screening; transplant evaluation maintenance if MCS-bridged or NYHA IV; long-term complication management (autonomic, neuropathy, atrial myopathy AF)
12. lifelong tafamidis if ATTR 61 mg PO daily PO daily — ATTR-CM diagnosed (ATTR-ACT — lifelong therapy; benefit 12-30 mo)
13. gene silencer addition if progression on tafamidis vutrisiran 25 mg SC q3 mo (or patisiran 0.3 mg/kg IV q3w) SC/IV q3 mo or q3 weeks — Progression on tafamidis or polyneuropathy component (HELIOS-A + APOLLO — gene silencers add benefit beyond stabilizer alone)
14. Dara-CyBorD until hematologic CR for AL per protocol with q4w maintenance SC weekly to monthly — AL amyloidosis active (ANDROMEDA — continue until durable CR)
15. autologous SCT for selected AL high-dose melphalan + autologous stem cell rescue IV one-time conditioning — Mayo Stage I-II AL without high-risk features + age <70 + good performance status (Selected AL patients benefit from HSCT consolidation)

Non-pharmacologic actions:
- Annual influenza + pneumococcal + COVID-19 + zoster vaccination
- Family ATTRv pedigree screening + genetic counseling
- Transplant team annual evaluation if NYHA III-IV
- Cardio-amyloid center quarterly visit
- Hematology q4-12w during AL chemo, then per response
- Falls clinic + autonomic dysfunction management
- Cardiac rehab maintenance phase if MCS-recovered

AVOID / contraindication checks:
- Digoxin_AVOID_in_cardiac_amyloidosis (binds amyloid fibrils → toxicity at low serum levels per ESC 2023 PMID 37596926 + Kittleson ACC/AHA 2023)
- Beta_blocker_AVOID_in_cardiac_amyloidosis (autonomic + amyloid heart fragility — hypotension, bradycardia, worsening output)
- Diltiazem_verapamil_AVOID_in_cardiac_amyloidosis (binds amyloid fibrils + AV block precipitant — non DHP CCB contraindicated)
- Ace_inhibitor_arb_caution_in_cardiac_amyloidosis (orthostasis, hypotension — usually poorly tolerated; may need dose reduction or discontinuation)
- Large_volume_diuresis_AVOID_in_cardiac_amyloidosis (preload dependent — hypotension, RAS activation, CR rise; gentle diuresis only)
- Typical_inotropes_AVOID_in_cardiac_amyloidosis_cs (dobutamine / milrinone often paradoxically worse — worsen LVOT obstruction, ventricular arrhythmia, autonomic instability per ESC 2023; norepinephrine first line)
- Tafamidis_no_renal_dose_adjustment_needed (lifelong therapy; benefit takes 12 30 months)
- Bortezomib_dose_reduce_for_neuropathy (existing ATTR neuropathy may worsen — neuro monitoring required)
- Daratumumab_pjp_prophylaxis_required (B cell depletion → infection risk; bactrim or atovaquone if sulfa allergy)

Monitoring

Regimen monitoring:
- continuous hemodynamics in cicu until off pressors
- daily lactate clearance trajectory
- daily weight and BMP with gentle diuresis only
- NT proBNP trend weekly for disease response
- echo at 6 months on tafamidis then annually (response 12-30 mo)
- free light chain weekly during AL chemo (hematologic response marker)
- LFT q2w during daratumumab (hepatotoxicity surveillance)
- CBC with diff q weekly during AL chemo (neutropenia risk + sepsis)
- PJP prophylaxis during daratumumab (bactrim or atovaquone)
- family ATTRv screening if variant TTR detected
- transplant evaluation if NYHA III IV or MCS dependent

Setting (outpatient) monitoring:
- Quarterly clinical + labs
- Annual echo with strain + 6MWD
- TTR levels if gene silencer
- Free light chains q4-12w if AL
- Family screening progress

Follow-up plan: Cardiology amyloid center quarterly; advanced HF / transplant team monthly if MCS-dependent; hematology q2-4w during AL chemo; ID surveillance during AL therapy (PJP prophylaxis); family ATTRv screening; cardiac rehab if MCS recovery achieved
- Close-out criterion: Long-term follow-up booked + amyloid-center handoff complete + family screening initiated

Monitoring phase: Continuous hemodynamics, daily weight (gentle diuresis), BMP, lactate clearance; AL: monitor FLC weekly during chemotherapy, LFT for daratumumab; ATTR: NT-proBNP + 6MWD + echo at 6 mo on tafamidis (response usually 12-30 mo)

Disposition

Current setting: outpatient — Quarterly cardio-amyloid center surveillance: NT-proBNP + 6MWD + echo + free light chains (AL) trends; tafamidis benefit assessment at 12-30 mo; ATTRv family screening; transplant evaluation maintenance if MCS-bridged or NYHA IV; long-term complication management (autonomic, neuropathy, atrial myopathy AF)

Disposition criteria:
- Stable on disease-modifying therapy + tolerating supportive regimen + family screening complete → continued long-term cardio-amyloid center care
- Progression despite max therapy → transplant evaluation or palliative care

Escalation triggers (move to higher acuity):
- Recurrent shock → ED + CICU + MCS evaluation
- AL relapse on FLC → hematology + second-line therapy
- ATTR progression → add gene silencer + transplant evaluation
- New high-grade AV block → EP urgent (rare in amyloid but reported)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Patient with cardiac amyloidosis inadvertently prescribed digoxin (binds amyloid fibrils → toxicity at therapeutic-range serum levels) — emergency: stop digoxin, supportive care, digibind for severe toxicity
- [LIFE_THREATENING] Refractory amyloid CS despite NE + IABP — escalate to Impella 5.5 or VA-ECMO bridge to disease-modifying therapy onset (months) or transplant; LV unable to recover quickly without therapy onset
- [LIFE_THREATENING] AL amyloidosis with cardiac stage III-IV (NT-proBNP >1800, troponin >0.025, dFLC >18) at presentation — oncologic emergency with median survival <6 months without urgent Dara-CyBorD; treatment must start within 48-72 h

Citations

- ESC 2023 cardiac amyloidosis position statement (PMID 37596926); ATTR-ACT (Maurer NEJM 2018, PMID 30145930); ANDROMEDA (Kumar PMID 34077641); SCAI 2022 CS staging (Naidu PMID 35718438); Kittleson ACC/AHA 2023 cardiac amyloidosis expert decision pathway [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 30144829) [PMID:30144829](https://pubmed.ncbi.nlm.nih.gov/30144829/)
- Cited evidence (PMID 35262029) [PMID:35262029](https://pubmed.ncbi.nlm.nih.gov/35262029/)
- Cited evidence (PMID 34077641) [PMID:34077641](https://pubmed.ncbi.nlm.nih.gov/34077641/)

Last reconciled with current guidelines: 2026-05-15.
References
  • ESC 2023 cardiac amyloidosis position statement (PMID 37596926); ATTR-ACT (Maurer NEJM 2018, PMID 30145930); ANDROMEDA (Kumar PMID 34077641); SCAI 2022 CS staging (Naidu PMID 35718438); Kittleson ACC/AHA 2023 cardiac amyloidosis expert decision pathway — PMID:37596926
  • Cited evidence (PMID 30145930) — PMID:30145930
  • Cited evidence (PMID 30144829) — PMID:30144829
  • Cited evidence (PMID 35262029) — PMID:35262029
  • Cited evidence (PMID 34077641) — PMID:34077641