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cardio.acute-hf.fabry-cardiomyopathy.v1PRODUCTION
cardio.acute-hf.fabry-cardiomyopathy.v1

ADHF in Fabry cardiomyopathy

cardiologyacuteadult
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Detailed

Fabry cardiomyopathy presenting as ADHF — phenotype-first triage (genotype-amenable for migalastat vs requires ERT vs advanced refractory)

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Fabry suspected

Patient inputs (13)

Diagnostic in males (<1% activity); intermediate in carrier females (unreliable — must do GLA sequencing)

Mandatory in females; confirms in males with intermediate enzyme activity; identifies mutation for amenability check (migalastat eligibility) and family cascade

Basal inferolateral mid-wall LGE + LOW native T1 (<950 ms at 1.5T) — pathognomonic Fabry per Sado/Pica PMID 24875668

Classic Fabry presents 25-50 in males (cardiac), 40-60 in females (cardiac variant); pediatric onset in classic males

X-linked: hemizygous males early/severe; heterozygous females variable due to X-inactivation

X-linked cardiomyopathy / renal failure / stroke / neuropathic pain in male relatives → Fabry pedigree clue

Fabry nephropathy common; baseline before ERT (no renal dose adjustment) + ACEi/ARB; KDIGO 2026 staging

HF severity stratification + ERT response monitoring

Persistently elevated in Fabry (myocardial fibrosis); diagnostic ambiguity vs ACS

Fabry nephropathy screen — proteinuria often early sign before eGFR decline

Concentric LVH, papillary muscle hypertrophy, diastolic dysfunction; speckle tracking — basal-to-apex strain gradient differs from amyloid

Hypotension in advanced Fabry (autonomic dysfunction + restrictive physiology); narrow tolerance for diuretics

Plasma globotriaosylsphingosine — severity marker + ERT response monitoring; elevated in classic Fabry

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Severity triggers (5)

5 need judgement
  • informationallife_threateningicd_eligibility_per_hrs_2017_in_fabry
    Fabry cardiomyopathy with EF <35 + sustained VT despite ≥3 mo GDMT + ERT/migalastat OR extensive LGE on CMR (>15% LV mass per ESC 2022 VA emerging consensus)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningfabry_with_high_grade_av_block
    Mobitz II / 2:1 AV block / complete heart block in Fabry (infiltrative conduction disease) ± syncope
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepediatric_or_family_screening_genetic_counseling
    Pediatric Fabry case OR newly diagnosed adult triggers cascade screening of family (X-linked: mother of male is obligate carrier; all daughters of males obligate carriers; sons of females 50% affected)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereert_infusion_related_reaction
    Acute infusion reaction during ERT (chills, fever, urticaria, dyspnea, hypotension) — most common in first months of agalsidase beta
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateamenable_mutation_check_for_migalastat_eligibility
    Newly diagnosed Fabry — check GLA mutation amenability via FDA-approved in vitro assay before initiating ERT (offers oral migalastat alternative for ~35-50% of mutations)
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

Fabry cardiomyopathy ADHF — disease-modifying therapy phenotype (ESC 2023 cardiomyopathies PMID 37622666 + FOS/Fabry Registry + ATTRACT PMID 27114250)
axis: fabry_cardiomyopathy_dmt_phenotype
Selected axis "Fabry cardiomyopathy ADHF — disease-modifying therapy phenotype (ESC 2023 cardiomyopathies PMID 37622666 + FOS/Fabry Registry + ATTRACT PMID 27114250)" by default fallback (first axis)
  • agalsidase beta
    first line
    enzyme_replacement_therapy_recombinant_alpha_galactosidase
    1 mg/kg IV every 2 weeks (premedicate with antihistamine + acetaminophen for infusion reaction prevention) • IV • every 2 weeks lifelong
    triggers: classic_fabry_diagnosed_male, fabry_with_significant_cardiac_or_renal_involvement
    FOS + Fabry Registry — slows progression of LV mass + eGFR decline + neuropathic pain; agalsidase beta (Fabrazyme) is US/EU standard
    rxcui 338817
  • agalsidase alfa
    first line
    enzyme_replacement_therapy_recombinant_alpha_galactosidase
    0.2 mg/kg IV every 2 weeks (Replagal — outside US) • IV • every 2 weeks lifelong
    triggers: classic_fabry_diagnosed_male_outside_us, agalsidase_beta_unavailable
    FOS — alternative ERT formulation; equivalent clinical efficacy in observational data
    rxcui 2691830
  • migalastat
    first line
    pharmacologic_chaperone_oral
    123 mg PO every other day (fasting state) • PO • every other day lifelong
    triggers: fabry_with_amenable_gla_mutation, patient_preference_for_oral_dmt
    ATTRACT (Hughes JMG 2017; PMID 27114250) — non-inferior to ERT in patients with amenable mutations (~35-50% of GLA variants); check amenability via FDA-approved in vitro assay before initiation
    rxcui 2054252
  • furosemide
    first line
    loop_diuretic
    20-40 mg IV (diuretic-naive starting per DOSE PMID 21366472) • IV • q12h with reassessment
    triggers: volume_overload_in_fabry_adhf
    Standard ADHF; gentle in Fabry HFpEF restrictive physiology — narrow preload window
    rxcui 4603
  • carvedilol
    first line
    beta_blocker_alpha1_combined
    3.125 mg PO BID, titrate q2wk to max tolerated • PO • BID
    triggers: residual_hfref_with_ef_below_40_in_fabry
    GDMT 4-pillar for residual HFrEF; CAPRICORN PMID 11356436
    rxcui 20352
  • sacubitril/valsartan
    first line
    arni_neprilysin_arb_combination
    24/26 mg PO BID, titrate to 97/103 mg BID • PO • BID
    triggers: residual_hfref_with_ef_below_40_in_fabry
    GDMT 4-pillar; PARADIGM-HF; PIONEER-HF in-hospital initiation PMID 30403955
    rxcui 1656328
  • spironolactone
    first line
    mineralocorticoid_receptor_antagonist
    25 mg PO daily, titrate to 50 mg if K + creatinine permit • PO • daily
    triggers: residual_hfref_with_ef_below_40_in_fabry
    GDMT 4-pillar; RALES + EMPHASIS-HF
    rxcui 9997
  • empagliflozin
    first line
    sglt2_inhibitor
    10 mg PO daily • PO • daily
    triggers: hfref_or_hfpef_in_fabry_with_egfr_above_20
    GDMT 4-pillar; EMPEROR-Reduced + EMPEROR-Preserved + EMPULSE PMID 35347356
    rxcui 1545653
  • warfarin
    comorbidity specific
    vitamin_k_antagonist
    5 mg PO daily, INR target 2-3 • PO • daily
    triggers: fabry_with_af_or_atrial_myopathy, intracardiac_thrombus_on_echo
    Fabry atrial myopathy → low CHA2DS2-VASc threshold for AC; warfarin or DOAC per individual choice (DOACs first-line for nonvalvular AF)
    rxcui 11289
  • apixaban
    first line
    doac_factor_xa_direct
    5 mg PO BID (or 2.5 mg BID per dose-reduction criteria) • PO • BID
    triggers: fabry_with_af_or_atrial_myopathy_no_apl
    DOAC first-line for nonvalvular AF in Fabry; preferred over warfarin per AHA/ACC/HRS 2023 AF guideline
    rxcui 1364430

outpatient playbook — drug actions (5)

  1. 1. continue ERT lifelong
    agalsidase beta 1 mg/kg IV q2wk • IV • every 2 weeks lifelong
    trigger: Fabry maintenance
    FOS + Fabry Registry
  2. 2. or continue migalastat lifelong if amenable
    rxcui 1808217
    123 mg PO QOD • PO • QOD lifelong
    trigger: amenable mutation maintenance
    ATTRACT PMID 27114250
  3. 3. continue GDMT 4-pillar if residual HFrEF
    rxcui 593411
    empagliflozin 10 mg + carvedilol + ARNI + MRA at max tolerated • PO • as scheduled
    trigger: EF <40 maintained
    ACC/AHA 2022 HF guideline
  4. 4. continue AC for AF or atrial myopathy
    rxcui 1364430
    apixaban 5 mg PO BID (or 2.5 mg BID per dose-reduction criteria) • PO • BID
    trigger: AF maintenance
    AHA/ACC/HRS 2023 AF guideline
  5. 5. continue ACEi/ARB for Fabry nephropathy
    rxcui 18867
    lisinopril 5-40 mg PO daily • PO • daily
    trigger: proteinuric Fabry nephropathy
    KDIGO 2026

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Concentric LVH on echo without HTN history, especially male age 25-50 or female with family history; LVH + proteinuria + neuropathic pain (acroparesthesia) or angiokeratomas → Fabry screen; Cardiac MRI basal inferolateral mid-wall LGE + low native T1 (<950 ms at 1.5T) — Fabry signature.

Objective

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

Assessment

**ADHF in Fabry cardiomyopathy** (cardio.acute-hf.fabry-cardiomyopathy.v1).
Phenotype framing: Fabry vs HCM (sarcomeric mutation; LGE patchy mid-wall; high T1) vs cardiac amyloidosis (apical sparing on strain; high T1; PYP+ for ATTR; SFLC+ for AL) vs hypertensive heart vs Danon disease (LAMP2 X-linked) vs PRKAG2
Scope: Fabry cardiomyopathy presenting as ADHF — phenotype-first triage (genotype-amenable for migalastat vs requires ERT vs advanced refractory)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Fabry cardiomyopathy ADHF — disease-modifying therapy phenotype (ESC 2023 cardiomyopathies PMID 37622666 + FOS/Fabry Registry + ATTRACT PMID 27114250)**.
1. agalsidase beta 1 mg/kg IV every 2 weeks (premedicate with antihistamine + acetaminophen for infusion reaction prevention) IV every 2 weeks lifelong (enzyme_replacement_therapy_recombinant_alpha_galactosidase, first line) — FOS + Fabry Registry — slows progression of LV mass + eGFR decline + neuropathic pain; agalsidase beta (Fabrazyme) is US/EU standard
2. agalsidase alfa 0.2 mg/kg IV every 2 weeks (Replagal — outside US) IV every 2 weeks lifelong (enzyme_replacement_therapy_recombinant_alpha_galactosidase, first line) — FOS — alternative ERT formulation; equivalent clinical efficacy in observational data
3. migalastat 123 mg PO every other day (fasting state) PO every other day lifelong (pharmacologic_chaperone_oral, first line) — ATTRACT (Hughes JMG 2017; PMID 27114250) — non-inferior to ERT in patients with amenable mutations (~35-50% of GLA variants); check amenability via FDA-approved in vitro assay before initiation
4. furosemide 20-40 mg IV (diuretic-naive starting per DOSE PMID 21366472) IV q12h with reassessment (loop_diuretic, first line) — Standard ADHF; gentle in Fabry HFpEF restrictive physiology — narrow preload window
5. carvedilol 3.125 mg PO BID, titrate q2wk to max tolerated PO BID (beta_blocker_alpha1_combined, first line) — GDMT 4-pillar for residual HFrEF; CAPRICORN PMID 11356436
6. sacubitril/valsartan 24/26 mg PO BID, titrate to 97/103 mg BID PO BID (arni_neprilysin_arb_combination, first line) — GDMT 4-pillar; PARADIGM-HF; PIONEER-HF in-hospital initiation PMID 30403955
7. spironolactone 25 mg PO daily, titrate to 50 mg if K + creatinine permit PO daily (mineralocorticoid_receptor_antagonist, first line) — GDMT 4-pillar; RALES + EMPHASIS-HF
8. empagliflozin 10 mg PO daily PO daily (sglt2_inhibitor, first line) — GDMT 4-pillar; EMPEROR-Reduced + EMPEROR-Preserved + EMPULSE PMID 35347356
9. warfarin 5 mg PO daily, INR target 2-3 PO daily (vitamin_k_antagonist, comorbidity specific) — Fabry atrial myopathy → low CHA2DS2-VASc threshold for AC; warfarin or DOAC per individual choice (DOACs first-line for nonvalvular AF)
10. apixaban 5 mg PO BID (or 2.5 mg BID per dose-reduction criteria) PO BID (doac_factor_xa_direct, first line) — DOAC first-line for nonvalvular AF in Fabry; preferred over warfarin per AHA/ACC/HRS 2023 AF guideline

Setting playbook (outpatient) — Long-term lysosomal storage center care: lifelong ERT or migalastat; GDMT for residual HFrEF; ICD eval per HRS 2017 / ESC 2022 VA if EF <35 + sustained VT or extensive LGE; family screening cascade; multi-organ surveillance (renal, neurologic, ophthalmologic, audiologic)
11. continue ERT lifelong agalsidase beta 1 mg/kg IV q2wk IV every 2 weeks lifelong — Fabry maintenance (FOS + Fabry Registry)
12. or continue migalastat lifelong if amenable 123 mg PO QOD PO QOD lifelong — amenable mutation maintenance (ATTRACT PMID 27114250)
13. continue GDMT 4-pillar if residual HFrEF empagliflozin 10 mg + carvedilol + ARNI + MRA at max tolerated PO as scheduled — EF <40 maintained (ACC/AHA 2022 HF guideline)
14. continue AC for AF or atrial myopathy apixaban 5 mg PO BID (or 2.5 mg BID per dose-reduction criteria) PO BID — AF maintenance (AHA/ACC/HRS 2023 AF guideline)
15. continue ACEi/ARB for Fabry nephropathy lisinopril 5-40 mg PO daily PO daily — proteinuric Fabry nephropathy (KDIGO 2026)

Non-pharmacologic actions:
- Family GLA genotype screening + cascade through generations
- Advanced HF / transplant program referral when DMT inadequate (Fabry can be transplanted; ERT continued post-transplant)
- Patient education + reproductive counseling
- Pediatric case → mother + siblings cascade screen mandatory

AVOID / contraindication checks:
- Migalastat_only_for_amenable_mutations (FDA approved in vitro assay required before initiation)
- Ert_infusion_reaction_premedicate (antihistamine + acetaminophen ± steroids)
- Digoxin_caution_in_advanced_fabry (some restrictive physiology overlap with amyloid; not absolute contraindication but caution warranted)
- Live_vaccines_safe_in_fabry (no immunosuppression)

Monitoring

Regimen monitoring:
- lyso gb3 at 3 6 months on dmt response marker
- echo at 12 months for lv mass response
- cmr at 12 24 months for lge progression
- egfr q 3 months for fabry nephropathy progression
- ecg q 6 months for conduction disease progression
- audiometry annually
- ophthalmology annually for cornea verticillata

Setting (outpatient) monitoring:
- Quarterly clinic + annual full restage
- CMR every 12-24 mo
- Cross-link to advanced HF if NYHA III on max DMT

Follow-up plan: Lifelong ERT or chaperone therapy; GDMT for residual HFrEF; ICD per HRS 2017 / ESC 2022 VA if EF <35 + sustained VT or extensive LGE; family screening cascade; multidisciplinary lysosomal storage disease center
- Close-out criterion: long-term plan booked

Monitoring phase: Daily weight + BMP; weekly NT-proBNP early; ERT infusion tolerance; lyso-Gb3 trend at 3-6 mo on therapy; echo + CMR at 12 mo for LV mass response

Disposition

Current setting: outpatient — Long-term lysosomal storage center care: lifelong ERT or migalastat; GDMT for residual HFrEF; ICD eval per HRS 2017 / ESC 2022 VA if EF <35 + sustained VT or extensive LGE; family screening cascade; multi-organ surveillance (renal, neurologic, ophthalmologic, audiologic)

Disposition criteria:
- Long-term lysosomal storage center 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 evaluation
- New conduction disease → PPM/ICD eval per HRS 2017
- New stroke → TEE for intracardiac thrombus + AC reassessment

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Fabry cardiomyopathy with EF <35 + sustained VT despite ≥3 mo GDMT + ERT/migalastat OR extensive LGE on CMR (>15% LV mass per ESC 2022 VA emerging consensus)
- [LIFE_THREATENING] Mobitz II / 2:1 AV block / complete heart block in Fabry (infiltrative conduction disease) ± syncope
- [SEVERE] Pediatric Fabry case OR newly diagnosed adult triggers cascade screening of family (X-linked: mother of male is obligate carrier; all daughters of males obligate carriers; sons of females 50% affected)

Citations

- ESC 2023 cardiomyopathies guideline (PMID 37622666) + Fabry Outcome Survey (FOS) + Fabry Registry + ATTRACT migalastat (PMID 27114250) + ACMG 2018 Fabry genetic testing + HRS 2017 SCD prevention (PMID 28219760) [PMID:37622666](https://pubmed.ncbi.nlm.nih.gov/37622666/)
- Cited evidence (PMID 27114250) [PMID:27114250](https://pubmed.ncbi.nlm.nih.gov/27114250/)
- Cited evidence (PMID 24875668) [PMID:24875668](https://pubmed.ncbi.nlm.nih.gov/24875668/)
- Cited evidence (PMID 28219760) [PMID:28219760](https://pubmed.ncbi.nlm.nih.gov/28219760/)
- Cited evidence (PMID 21366472) [PMID:21366472](https://pubmed.ncbi.nlm.nih.gov/21366472/)

Last reconciled with current guidelines: 2026-05-15.
References
  • ESC 2023 cardiomyopathies guideline (PMID 37622666) + Fabry Outcome Survey (FOS) + Fabry Registry + ATTRACT migalastat (PMID 27114250) + ACMG 2018 Fabry genetic testing + HRS 2017 SCD prevention (PMID 28219760) — PMID:37622666
  • Cited evidence (PMID 27114250) — PMID:27114250
  • Cited evidence (PMID 24875668) — PMID:24875668
  • Cited evidence (PMID 28219760) — PMID:28219760
  • Cited evidence (PMID 21366472) — PMID:21366472