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cardio.acute-hf.transplant-recipient.v1PRODUCTION
cardio.acute-hf.transplant-recipient.v1

ADHF in cardiac transplant recipient (CAV / ACR / AMR)

cardiologyacuteadult
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11/12 authored

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

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Detailed

Heart transplant recipient with acute decompensation — differential is allograft-specific (CAV vs ACR vs AMR vs non-allograft causes); inherits ADHF arc from cardio.acute-hf.core.v1

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transplant context confirmed

Patient inputs (12)

Donor-specific antibodies — required for AMR diagnosis (ISHLT 2013 AMR criteria)

Gold standard for ACR grading (ISHLT 2010 1R/2R/3R) and AMR (pAMR0–pAMR3)

Recipient age + transplant vintage shape CAV vs rejection probability

Time post-transplant: <1 yr → ACR/AMR dominate; >5 yr → CAV dominates (ISHLT 2023)

Tacrolimus/cyclosporine (CNI) trough levels + MMF + prednisone regimen drives differential and adjustment plan

CNI nephrotoxicity baseline; informs imaging contrast safety + diuretic dosing

Sub-therapeutic CNI trough → rejection risk; supratherapeutic → toxicity (KDIGO transplant 2009)

Graft injury marker; persistent rise without ischemia → rejection until proven otherwise

Diagnostic + monitoring; rises with both rejection and CAV-driven dysfunction

STAT echo for new LV/RV dysfunction; restrictive pattern can suggest rejection

Hypotension + graft dysfunction → cardiogenic shock pathway; CNI-related vasoplegia possible

CAV diagnosis + staging (ISHLT CAV 1/2/3 per stenosis severity + LV dysfunction)

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Severity triggers (5)

5 need judgement
  • informationallife_threateningantibody_mediated_rejection_with_lv_dysfunction
    Endomyocardial biopsy pAMR2 or pAMR3 + DSA positive + new LVEF reduction
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningacr_grade_3r_on_endomyocardial_biopsy
    ISHLT 2010 grade 3R ACR (severe acute cellular rejection with myocyte damage)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningcardiogenic_shock_in_transplant_recipient
    Transplant recipient with SBP <90 + lactate ≥2 + new severe LV/RV dysfunction (graft failure)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverecav_ishlt_grade_3_with_lv_dysfunction
    Cardiac allograft vasculopathy ISHLT grade 3 (severe distal pruning + LVEF <45) on annual surveillance
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresubtherapeutic_cni_trough_with_active_rejection
    Tacrolimus trough <5 ng/mL early or <4 ng/mL late + biopsy-proven active rejection
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

Cardiac transplant ADHF — rejection / CAV phenotype-based regimen (ISHLT 2010 + 2023; KDIGO transplant 2009)
axis: transplant_rejection_phenotype
Selected axis "Cardiac transplant ADHF — rejection / CAV phenotype-based regimen (ISHLT 2010 + 2023; KDIGO transplant 2009)" by default fallback (first axis)
  • methylprednisolone
    first line
    corticosteroid
    1000 mg IV daily × 3 days (pulse therapy) • IV • daily × 3
    triggers: acr_grade_2r_or_higher, amr_with_lv_dysfunction
    ISHLT 2010 (Stewart PMID 21177015) — pulse steroids first line for ≥2R ACR; also adjunct in AMR
    rxcui 6902
  • mycophenolate mofetil
    add on
    antiproliferative_immunosuppressant
    1000–1500 mg PO BID (continue maintenance; do not hold for rejection) • PO • BID
    triggers: transplant_maintenance
    ISHLT 2023 maintenance triple therapy (CNI + MMF + steroids); continue during rejection treatment
    rxcui 68149
  • tacrolimus
    first line
    calcineurin_inhibitor
    Maintain trough 8–12 ng/mL early post-transplant; 5–10 ng/mL late; AVOID over-reduction • PO • BID
    triggers: transplant_maintenance, sub_therapeutic_trough_with_rejection
    KDIGO transplant 2009 — narrow therapeutic window; sub-therapeutic trough is the most modifiable rejection driver
    rxcui 42316
  • rituximab
    add on
    anti_cd20_monoclonal_antibody
    375 mg/m² IV weekly × 4 • IV • weekly × 4
    triggers: amr_pamr2_or_pamr3, dsa_high_titer
    AMR B-cell depletion; ISHLT 2013 AMR working formulation
    rxcui 121191
  • immune globulin (IVIG)
    add on
    pooled_immunoglobulin
    1–2 g/kg IV (split over 2–5 days) • IV • one course (often combined with plasmapheresis)
    triggers: amr_pamr2_or_pamr3
    AMR neutralization of circulating DSA; combined with plasmapheresis per ISHLT 2013
    rxcui 1426680
  • torsemide
    first line
    loop_diuretic
    20–40 mg IV/PO • IV/PO • daily–BID
    triggers: volume_overload_in_transplant_recipient
    Decongestion; preferred over furosemide if gut edema (TRANSFORM-HF Mentz JAMA 2023); avoid NSAIDs
    rxcui 38413

outpatient playbook — drug actions (3)

  1. 1. continue triple immunosuppression long-term
    rxcui 42316
    tacrolimus trough 5–8 ng/mL late + MMF 1000 BID + prednisone 2.5–5 daily • PO • as scheduled
    trigger: transplant maintenance
    ISHLT 2023; lower troughs late to balance CAV/malignancy/infection vs rejection risk
  2. 2. statin for CAV prevention
    rxcui 617314
    pravastatin 20–40 mg daily (preferred — lowest CYP3A4 interaction with CNI) • PO • daily
    trigger: transplant maintenance — CAV prevention
    ISHLT 2023 Class I; Kobashigawa NEJM 1995 transplant statin trial
  3. 3. consider mTOR switch (sirolimus/everolimus) for CAV progression
    rxcui 35302
    sirolimus per trough 4–8 ng/mL; reduce CNI • PO • daily
    trigger: CAV progression on annual angio
    mTOR slows CAV progression; CRAD trial

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Heart transplant recipient with new dyspnea / orthopnea / edema (concern for rejection or CAV); Unexplained troponin or BNP rise in transplant recipient (rejection screen); New LVEF reduction on surveillance echo in transplant recipient.

Objective

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

Assessment

**ADHF in cardiac transplant recipient (CAV / ACR / AMR)** (cardio.acute-hf.transplant-recipient.v1).
Phenotype framing: Assign rejection class — ACR 1R/2R/3R per ISHLT 2010 (PMID 21177015); AMR pAMR0/pAMR1/pAMR2/pAMR3; CAV ISHLT 1/2/3; non-allograft (sepsis, PE, CNI cardiotoxicity)
Scope: Heart transplant recipient with acute decompensation — differential is allograft-specific (CAV vs ACR vs AMR vs non-allograft causes); inherits ADHF arc from cardio.acute-hf.core.v1

No severity triggers fired against current inputs.

Plan

Regimen axis: **Cardiac transplant ADHF — rejection / CAV phenotype-based regimen (ISHLT 2010 + 2023; KDIGO transplant 2009)**.
1. methylprednisolone 1000 mg IV daily × 3 days (pulse therapy) IV daily × 3 (corticosteroid, first line) — ISHLT 2010 (Stewart PMID 21177015) — pulse steroids first line for ≥2R ACR; also adjunct in AMR
2. mycophenolate mofetil 1000–1500 mg PO BID (continue maintenance; do not hold for rejection) PO BID (antiproliferative_immunosuppressant, add on) — ISHLT 2023 maintenance triple therapy (CNI + MMF + steroids); continue during rejection treatment
3. tacrolimus Maintain trough 8–12 ng/mL early post-transplant; 5–10 ng/mL late; AVOID over-reduction PO BID (calcineurin_inhibitor, first line) — KDIGO transplant 2009 — narrow therapeutic window; sub-therapeutic trough is the most modifiable rejection driver
4. rituximab 375 mg/m² IV weekly × 4 IV weekly × 4 (anti_cd20_monoclonal_antibody, add on) — AMR B-cell depletion; ISHLT 2013 AMR working formulation
5. immune globulin (IVIG) 1–2 g/kg IV (split over 2–5 days) IV one course (often combined with plasmapheresis) (pooled_immunoglobulin, add on) — AMR neutralization of circulating DSA; combined with plasmapheresis per ISHLT 2013
6. torsemide 20–40 mg IV/PO IV/PO daily–BID (loop_diuretic, first line) — Decongestion; preferred over furosemide if gut edema (TRANSFORM-HF Mentz JAMA 2023); avoid NSAIDs

Setting playbook (outpatient) — Long-term transplant cardiology surveillance: annual coronary angiography or IVUS for CAV (years 1, 3, 5, then per program), surveillance biopsy schedule, DSA monitoring, secondary-prevention bundle, malignancy screening (PTLD, skin cancer)
7. continue triple immunosuppression long-term tacrolimus trough 5–8 ng/mL late + MMF 1000 BID + prednisone 2.5–5 daily PO as scheduled — transplant maintenance (ISHLT 2023; lower troughs late to balance CAV/malignancy/infection vs rejection risk)
8. statin for CAV prevention pravastatin 20–40 mg daily (preferred — lowest CYP3A4 interaction with CNI) PO daily — transplant maintenance — CAV prevention (ISHLT 2023 Class I; Kobashigawa NEJM 1995 transplant statin trial)
9. consider mTOR switch (sirolimus/everolimus) for CAV progression sirolimus per trough 4–8 ng/mL; reduce CNI PO daily — CAV progression on annual angio (mTOR slows CAV progression; CRAD trial)

Non-pharmacologic actions:
- Annual CAV imaging
- Sun protection + dermatology yearly
- Vaccinations (no live)
- Adherence reinforcement

AVOID / contraindication checks:
- Nsaid_avoid_absolutely (allograft nephrotoxicity; CNI synergistic AKI)
- Cni_minimal_reduction_only (over reduction precipitates rejection — narrow therapeutic window)
- Live_vaccines_contraindicated (chronic immunosuppression)
- Interaction:cni_with_clarithromycin_diltiazem_azole (CYP3A4 — toxic CNI levels)

Monitoring

Regimen monitoring:
- cni trough daily during rejection workup
- troponin q12h x 48h post treatment
- surveillance emb at 2 4 12 weeks post rejection treatment
- dsa titer q month x 3 post amr

Setting (outpatient) monitoring:
- Quarterly clinic + labs
- Annual CAV imaging + DSA + cancer screen

Monitoring phase: Repeat troponin q12h × 48 h; CNI troughs daily; surveillance biopsy at 2 wk, 4 wk, 12 wk after rejection treatment; DSA q month × 3 (ISHLT 2023)

Disposition

Current setting: outpatient — Long-term transplant cardiology surveillance: annual coronary angiography or IVUS for CAV (years 1, 3, 5, then per program), surveillance biopsy schedule, DSA monitoring, secondary-prevention bundle, malignancy screening (PTLD, skin cancer)

Disposition criteria:
- Long-term continuation with transplant program; cross-link to cardio.hf.core.v1 for residual HFrEF management

Escalation triggers (move to higher acuity):
- New LV dysfunction → STAT biopsy + DSA
- CAV ISHLT 3 progression → re-transplant evaluation
- PTLD suspicion → reduce immunosuppression + oncology consult

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Endomyocardial biopsy pAMR2 or pAMR3 + DSA positive + new LVEF reduction
- [LIFE_THREATENING] ISHLT 2010 grade 3R ACR (severe acute cellular rejection with myocyte damage)
- [LIFE_THREATENING] Transplant recipient with SBP <90 + lactate ≥2 + new severe LV/RV dysfunction (graft failure)

Citations

- ISHLT 2010 ACR grading + ISHLT 2013 AMR working formulation + ISHLT 2023 update + KDIGO transplant 2009 [PMID:21177015](https://pubmed.ncbi.nlm.nih.gov/21177015/)
- Cited evidence (PMID 23446352) [PMID:23446352](https://pubmed.ncbi.nlm.nih.gov/23446352/)
- Cited evidence (PMID 25997674) [PMID:25997674](https://pubmed.ncbi.nlm.nih.gov/25997674/)
- Cited evidence (PMID 26277690) [PMID:26277690](https://pubmed.ncbi.nlm.nih.gov/26277690/)
- Cited evidence (PMID 32067844) [PMID:32067844](https://pubmed.ncbi.nlm.nih.gov/32067844/)

Last reconciled with current guidelines: 2026-05-14.
References