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cardio.acute-hf.fabry-cardiomyopathy.v1

ADHF in Fabry cardiomyopathy

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Start encounter →Print handoutPRODUCTION

Phase E adjacent-disease variant of cardio.acute-hf.core.v1 — narrowed to ADHF in Fabry cardiomyopathy (X-linked lysosomal storage disorder, GLA deficiency). Phenotype-first triage drives DMT selection (ERT vs migalastat per amenability). Diagnostic algorithm: serum α-Gal A activity (males <1% diagnostic) + GLA gene sequencing (mandatory in females; confirms in males with intermediate enzyme) + plasma lyso-Gb3 (severity marker); cardiac MRI with T1 mapping (basal inferolateral mid-wall LGE + LOW native T1 <950 ms at 1.5T per Sado/Pica PMID 24875668) — pathognomonic Fabry signature distinguishing from amyloid (high T1) and HCM (normal/high T1). DMT options: ERT (agalsidase beta 1 mg/kg IV q2wk OR agalsidase alfa 0.2 mg/kg IV q2wk) per FOS + Fabry Registry, OR migalastat 123 mg PO QOD for amenable mutations per ATTRACT (PMID 27114250) — check amenability via FDA-approved in vitro assay. Family screening cascade MANDATORY (X-linked: mother of male is obligate carrier; all daughters of male obligate carriers; sons of females 50% affected). Pediatric case → cascade screen mother + siblings. ICD eval per HRS 2017 (PMID 28219760) if EF <35 + sustained VT despite ≥3 mo GDMT + DMT, or per ESC 2022 VA guideline if extensive LGE on CMR. Manifest pointer reuses cardio.acute-hf.core.v1 manifest. Design-brief reuses parent. Status INTEGRATED; authored 2026-05-15 by shard-06-cardio-acute (Phase E wave 22 systemic-disease).

Entry points (4)

  • symptom
    Concentric LVH on echo without HTN history, especially male age 25-50 or female with family history
    unexplained_lvh_in_young_or_middle_aged_adult
  • symptom
    LVH + proteinuria + neuropathic pain (acroparesthesia) or angiokeratomas → Fabry screen
    lvh_with_proteinuria_neuropathic_pain_or_angiokeratomas
  • imaging
    Cardiac MRI basal inferolateral mid-wall LGE + low native T1 (<950 ms at 1.5T) — Fabry signature
    cmr_basal_inferolateral_lge_with_low_t1
  • history
    Family history of unexplained cardiomyopathy, renal failure, or stroke (X-linked inheritance pattern)
    family_history_of_unexplained_cardiomyopathy_or_renal_failure

Required inputs (13)

  • agerequired
    demographic • used at CONTEXT
    Classic Fabry presents 25-50 in males (cardiac), 40-60 in females (cardiac variant); pediatric onset in classic males
  • sexrequired
    demographic • used at CONTEXT
    X-linked: hemizygous males early/severe; heterozygous females variable due to X-inactivation
  • family_history_x_linked_patternrequired
    history • used at CONTEXT
    X-linked cardiomyopathy / renal failure / stroke / neuropathic pain in male relatives → Fabry pedigree clue
  • sbprequired
    vital • used at RED_FLAGS
    Hypotension in advanced Fabry (autonomic dysfunction + restrictive physiology); narrow tolerance for diuretics
  • nt_probnprequired
    lab • used at INITIAL_WORKUP
    HF severity stratification + ERT response monitoring
  • troponinrequired
    lab • used at INITIAL_WORKUP
    Persistently elevated in Fabry (myocardial fibrosis); diagnostic ambiguity vs ACS
  • creatininerequired
    lab • used at CONTEXT
    Fabry nephropathy common; baseline before ERT (no renal dose adjustment) + ACEi/ARB; KDIGO 2026 staging
  • urinalysis_with_proteinrequired
    lab • used at INITIAL_WORKUP
    Fabry nephropathy screen — proteinuria often early sign before eGFR decline
  • alpha_galactosidase_a_activityrequired
    lab • used at BRANCHING_WORKUP
    Diagnostic in males (<1% activity); intermediate in carrier females (unreliable — must do GLA sequencing)
  • gla_gene_sequencingrequired
    lab • used at BRANCHING_WORKUP
    Mandatory in females; confirms in males with intermediate enzyme activity; identifies mutation for amenability check (migalastat eligibility) and family cascade
  • plasma_lyso_gb3
    lab • used at BRANCHING_WORKUP
    Plasma globotriaosylsphingosine — severity marker + ERT response monitoring; elevated in classic Fabry
  • echo_with_strainrequired
    imaging • used at INITIAL_WORKUP
    Concentric LVH, papillary muscle hypertrophy, diastolic dysfunction; speckle tracking — basal-to-apex strain gradient differs from amyloid
  • cardiac_mri_with_t1_mappingrequired
    imaging • used at BRANCHING_WORKUP
    Basal inferolateral mid-wall LGE + LOW native T1 (<950 ms at 1.5T) — pathognomonic Fabry per Sado/Pica PMID 24875668

12-phase flow (12)

  1. 1FRAME
    Fabry cardiomyopathy presenting as ADHF — phenotype-first triage (genotype-amenable for migalastat vs requires ERT vs advanced refractory)
    inputs: age, sex
    advance: Fabry suspected
  2. 2ENTRY
    LVH without HTN, especially male 25-50 or female with family history; LVH + proteinuria + neuropathic pain or angiokeratomas; CMR basal inferolateral LGE + low T1
    inputs: age, sex
    advance: one entry trigger present
  3. 3CONTEXT
    Demographics, family history (X-linked pattern), systemic features (renal, neurologic, dermatologic, ophthalmologic), baseline renal function (KDIGO 2026)
    inputs: age, sex, family_history_x_linked_pattern, sbp, creatinine
    advance: context complete
  4. 4RED_FLAGS
    Cardiogenic shock; diuretic-precipitated hypotension (restrictive physiology); high-grade AV block (Fabry conduction disease); ERT-related infusion reaction; pediatric case requiring family screening cascade
    inputs: sbp, troponin, nt_probnp
    actions: cardiogenic_shock
    advance: red flags screened or escalated
  5. 5INITIAL_WORKUP
    NT-proBNP + troponin + BMP + CBC + UA + ECG (PR shortening early, then AV block) + bedside echo with strain
    inputs: nt_probnp, troponin, creatinine, urinalysis_with_protein, echo_with_strain
    actions: acute_pulm_edema, panel.cardiac, panel.renal
    advance: baseline workup documented
  6. 6BRANCHING_WORKUP
    Serum α-Gal A activity (males); GLA gene sequencing (females mandatory; males if borderline); plasma lyso-Gb3; cardiac MRI with T1 mapping (basal inferolateral LGE + low T1 signature); systemic features (slit lamp for cornea verticillata, EMG/skin biopsy for small-fiber neuropathy)
    inputs: alpha_galactosidase_a_activity, gla_gene_sequencing, cardiac_mri_with_t1_mapping
    advance: Fabry diagnosis confirmed (enzyme + genotype) and amenability assessed
  7. 7DIFFERENTIAL
    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
    inputs: gla_gene_sequencing, cardiac_mri_with_t1_mapping
    advance: etiology assigned + mimics excluded
  8. 8RISK_STRATIFICATION
    Mainz Severity Score Index (MSSI); cardiac involvement severity (LV mass, LGE burden, EF); concurrent renal involvement (eGFR, proteinuria); neurologic involvement; sudden death risk per HRS 2017 + ESC 2022 VA
    inputs: nt_probnp, troponin, creatinine
    advance: severity stratified
  9. 9TREATMENT
    Standard ADHF (gentle diuresis) + DISEASE-MODIFYING THERAPY: ERT (agalsidase alfa or beta IV q2wk) OR migalastat 123 mg PO QOD if amenable mutation; GDMT 4-pillar for residual HFrEF; AVOID amyloid-style cautions adapted (Fabry typically tolerates GDMT better than amyloid)
    inputs: sbp, creatinine, gla_gene_sequencing
    actions: protocol.cardiogenic_shock
    advance: DMT + supportive plan started
  10. 10DISPOSITION
    Floor vs ICU; lysosomal storage disease specialty center referral; family screening cascade initiated
    advance: unit + multidisciplinary team assigned
  11. 11MONITORING
    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
    inputs: creatinine, nt_probnp
    actions: panel.renal
    advance: monitoring plan documented
  12. 12FOLLOWUP
    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
    advance: long-term plan booked