ADHF in cardiac transplant recipient (CAV / ACR / AMR)
Encounter flow
11/12 authoredCanonical 12-phase frame with authored status for this dossier.
Frame
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
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)
* = hard-required. Engine cannot meaningfully run until these are filled.
Severity triggers (5)
- informationallife_threateningantibody_mediated_rejection_with_lv_dysfunctionEndomyocardial biopsy pAMR2 or pAMR3 + DSA positive + new LVEF reductionTrigger could not be auto-evaluated — needs clinician judgement.
- informationallife_threateningacr_grade_3r_on_endomyocardial_biopsyISHLT 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_recipientTransplant 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_dysfunctionCardiac allograft vasculopathy ISHLT grade 3 (severe distal pruning + LVEF <45) on annual surveillanceTrigger could not be auto-evaluated — needs clinician judgement.
- informationalseveresubtherapeutic_cni_trough_with_active_rejectionTacrolimus trough <5 ng/mL early or <4 ng/mL late + biopsy-proven active rejectionTrigger could not be auto-evaluated — needs clinician judgement.
Workflow calculators
Run this disease's risk and dosing calculators inline.
Recommended regimen
Cardiac transplant ADHF — rejection / CAV phenotype-based regimen (ISHLT 2010 + 2023; KDIGO transplant 2009)- methylprednisolonefirst linecorticosteroid1000 mg IV daily × 3 days (pulse therapy) • IV • daily × 3triggers: acr_grade_2r_or_higher, amr_with_lv_dysfunctionISHLT 2010 (Stewart PMID 21177015) — pulse steroids first line for ≥2R ACR; also adjunct in AMRrxcui 6902
- mycophenolate mofetiladd onantiproliferative_immunosuppressant1000–1500 mg PO BID (continue maintenance; do not hold for rejection) • PO • BIDtriggers: transplant_maintenanceISHLT 2023 maintenance triple therapy (CNI + MMF + steroids); continue during rejection treatmentrxcui 68149
- tacrolimusfirst linecalcineurin_inhibitorMaintain trough 8–12 ng/mL early post-transplant; 5–10 ng/mL late; AVOID over-reduction • PO • BIDtriggers: transplant_maintenance, sub_therapeutic_trough_with_rejectionKDIGO transplant 2009 — narrow therapeutic window; sub-therapeutic trough is the most modifiable rejection driverrxcui 42316
- rituximabadd onanti_cd20_monoclonal_antibody375 mg/m² IV weekly × 4 • IV • weekly × 4triggers: amr_pamr2_or_pamr3, dsa_high_titerAMR B-cell depletion; ISHLT 2013 AMR working formulationrxcui 121191
- immune globulin (IVIG)add onpooled_immunoglobulin1–2 g/kg IV (split over 2–5 days) • IV • one course (often combined with plasmapheresis)triggers: amr_pamr2_or_pamr3AMR neutralization of circulating DSA; combined with plasmapheresis per ISHLT 2013rxcui 1426680
- torsemidefirst lineloop_diuretic20–40 mg IV/PO • IV/PO • daily–BIDtriggers: volume_overload_in_transplant_recipientDecongestion; preferred over furosemide if gut edema (TRANSFORM-HF Mentz JAMA 2023); avoid NSAIDsrxcui 38413
outpatient playbook — drug actions (3)
- 1. continue triple immunosuppression long-termrxcui 42316tacrolimus trough 5–8 ng/mL late + MMF 1000 BID + prednisone 2.5–5 daily • PO • as scheduledtrigger: transplant maintenanceISHLT 2023; lower troughs late to balance CAV/malignancy/infection vs rejection risk
- 2. statin for CAV preventionrxcui 617314pravastatin 20–40 mg daily (preferred — lowest CYP3A4 interaction with CNI) • PO • dailytrigger: transplant maintenance — CAV preventionISHLT 2023 Class I; Kobashigawa NEJM 1995 transplant statin trial
- 3. consider mTOR switch (sirolimus/everolimus) for CAV progressionrxcui 35302sirolimus per trough 4–8 ng/mL; reduce CNI • PO • dailytrigger: CAV progression on annual angiomTOR slows CAV progression; CRAD trial
Auto-drafted A&P note
outpatientSubjective
- 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.
- ISHLT 2010 ACR grading + ISHLT 2013 AMR working formulation + ISHLT 2023 update + KDIGO transplant 2009 — PMID:21177015
- Cited evidence (PMID 23446352) — PMID:23446352
- Cited evidence (PMID 25997674) — PMID:25997674
- Cited evidence (PMID 26277690) — PMID:26277690
- Cited evidence (PMID 32067844) — PMID:32067844