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cardio.nstemi.post-transplant-cav.v1

NSTEMI in heart-transplant recipient — cardiac allograft vasculopathy (CAV)-driven

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Phase E variant of cardio.nstemi.core.v1 — narrowed to NSTEMI in heart-transplant recipients driven by cardiac allograft vasculopathy (CAV). Pathophysiology: alloimmune-driven concentric coronary intimal hyperplasia per ISHLT 2010/2023; CMV-driven CAV acceleration per Hosenpud Lancet 1998 + Valantine 2004. Denervated grafts blunt classic angina — silent ischemia rule applies; any unexplained troponin rise + ECG changes + new LV dysfunction is NSTEMI-equivalent. Diagnostic specialization: coronary angiography + IVUS MANDATORY (CAV gold standard — intimal thickness >0.5 mm per Mehra PMID 26277690); cardiac MRI for CAV burden if eGFR ≥30; DSA + complement-binding (C1q) DSA + endomyocardial biopsy if concurrent rejection suspected; CMV PCR for active viremia + CAV acceleration screen. Treatment specialization: standard NSTE-ACS bundle BUT diffuse CAV may not be amenable to standard PCI; IVUS-guided PCI for focal lesions; CABG rare given diffuse pattern + redo-sternotomy risk; re-transplant evaluation if severe CAV + non-recoverable graft per ISHLT 2023. CYP3A4-safe statin only (pravastatin or pitavastatin per Kobashigawa NEJM 1995 PMID 7637810) — simvastatin/lovastatin CONTRAINDICATED with CNI. AVOID NSAIDs absolutely (allograft nephrotoxicity + CNI synergistic AKI). Cautious CCB selection (avoid diltiazem/verapamil with CNI — CYP3A4 toxicity; prefer amlodipine if BP control needed). Long-term: mTOR inhibitor (sirolimus, everolimus) substitution for CNI to slow CAV progression per CAVS-1 / CRAD trials + ISHLT 2024 update strongly considered after NSTEMI; annual CAV imaging (angio + IVUS); transplant program co-management mandatory; cross-link to cardio.acute-hf.transplant-recipient.v1 for residual HFrEF management; PJP prophylaxis lifelong; cancer surveillance (skin, PTLD). Sister-differentiated from cardio.stemi.transplant-recipient.v1 (transmural variant — same long-term workup, ECG presentation discriminates entry) and cardio.acute-hf.transplant-recipient.v1 (HF presentation — different presenting syndrome, shared immunosuppression context). Status INTEGRATED until terminology + RxNav-validated drug codes are reconciled. Authored 2026-05-15 by shard-06-cardio-acute Phase E wave 25.

Entry points (6)

  • lab_abnormality
    Unexplained hsTn rise/fall + ECG changes in heart-transplant recipient — NSTEMI-equivalent in denervated graft (silent ischemia rule); CAV-driven on differential
    unexplained_troponin_rise_in_transplant_recipient
  • symptom
    Heart-transplant recipient (denervated graft) with new dyspnea / fatigue / hypotension / syncope + non-ST-elevation ECG changes + troponin rise — silent ischemia pattern (no classic angina)
    transplant_recipient_with_silent_ischemia_dyspnea_or_fatigue
  • imaging
    Known CAV ISHLT grade 2-3 + new LV dysfunction on echo + troponin rise → emergent angiography for CAV-driven NSTEMI assessment with IVUS
    cav_progression_with_new_lv_dysfunction_or_troponin
  • history
    Heart-transplant recipient with precipitant (anemia, sepsis, hypoxia, tachycardia, dehydration) + troponin rise + ECG changes → CAV substrate + supply-demand mismatch NSTEMI
    transplant_recipient_with_anemia_or_sepsis_or_hypoxia_supply_demand
  • history
    Heart-transplant recipient with sub-therapeutic CNI trough + DSA positivity + new LV dysfunction + troponin rise → emergent biopsy + DSA panel + angio-IVUS workup
    transplant_recipient_with_concurrent_rejection_suspicion_and_troponin
  • imaging
    Heart-transplant recipient with new CMV PCR positivity + accelerated CAV on annual screen or new troponin rise (CMV-driven CAV acceleration per Hosenpud Lancet 1998)
    cmv_pcr_positive_with_new_cav_or_troponin_in_transplant

Required inputs (17)

  • agerequired
    demographic • used at CONTEXT
    Recipient age + transplant vintage shape CAV burden vs concurrent rejection probability; older patients more likely to have multi-territory CAV
  • transplant_date_and_vintagerequired
    history • used at CONTEXT
    Time post-transplant: <1 yr → ACR/AMR more likely co-driver; 1-5 yr → CAV emerging; >5 yr → CAV dominates per ISHLT 2023 registry data
  • current_immunosuppression_regimenrequired
    history • used at CONTEXT
    Tacrolimus / cyclosporine (CNI) trough levels + MMF + prednisone regimen drives differential and adjustment plan; CYP3A4 interactions with statins, CCB, antibiotics critical for medication safety
  • prior_cav_grade_and_imaging_historyrequired
    history • used at CONTEXT
    Known CAV ISHLT grade (1/2/3 per Mehra PMID 26277690) + IVUS history + prior PCI/CABG/re-transplant evaluation drives current management decisions
  • prior_rejection_episodes_and_dsa_statusrequired
    history • used at CONTEXT
    Prior ACR/AMR episodes + DSA positivity history + complement-binding (C1q) DSA + biopsy results inform current rejection probability and treatment plan
  • sbprequired
    vital • used at RED_FLAGS
    Hypotension + NSTEMI in transplant recipient → cardiogenic-shock pathway (DanGer Shock SCAI staging); CNI-related vasoplegia possible; SBP <90 triggers MCS evaluation + transplant program activation
  • hrrequired
    vital • used at CONTEXT
    Denervated graft has higher resting HR baseline (~90-110 bpm); tachycardia triggers supply-demand mismatch in CAV substrate; new tachyarrhythmia raises infection / rejection / volume status concerns
  • hs_troponin_serialrequired
    lab • used at INITIAL_WORKUP
    Defines NSTEMI per 4th UDMI (PMID 30153967) rise/fall criteria; chronic mild troponin elevation common in transplant recipients (CAV baseline) — ACUTE rise/fall above baseline drives NSTEMI label; persistent rise without ECG changes → rejection workup
  • nt_probnprequired
    lab • used at INITIAL_WORKUP
    Diagnostic + monitoring; rises with NSTEMI, CAV-driven dysfunction, and concurrent rejection; trended for decongestion if HF features present
  • creatinine_egfrrequired
    lab • used at INITIAL_WORKUP
    CNI nephrotoxicity baseline; informs imaging contrast safety + AC dosing + statin selection; AVOID NSAIDs absolutely (synergistic AKI with CNI); KDIGO 2021 race-free eGFR
  • cni_troughrequired
    lab • used at CONTEXT
    Sub-therapeutic CNI trough → concurrent rejection risk; supratherapeutic → toxicity (KDIGO transplant 2009); STAT trough on arrival drives immunosuppression adjustment
  • dsa_panel_and_c1q
    lab • used at BRANCHING_WORKUP
    Donor-specific antibodies + complement-binding (C1q) DSA assay — required if concurrent AMR suspected (ISHLT 2013 AMR criteria PMID 24263017); positive DSA + LV dysfunction triggers AMR pathway with plasmapheresis + IVIG + rituximab
  • cmv_pcrrequired
    lab • used at INITIAL_WORKUP
    CMV viremia accelerates CAV per Hosenpud Lancet 1998 + Valantine 2004 — drives preemptive valganciclovir treatment; also rules out CMV myocarditis ACS mimic
  • cbcrequired
    lab • used at INITIAL_WORKUP
    Anemia + leukopenia + thrombocytopenia common from immunosuppression; anemia worsens supply-demand mismatch in CAV substrate; baseline before any antiplatelet / AC
  • echo_statrequired
    imaging • used at INITIAL_WORKUP
    STAT echo for new LV/RV dysfunction; restrictive pattern can suggest concurrent rejection; baseline LVEF comparison critical for distinguishing acute event from chronic CAV trajectory
  • cor_angio_with_ivus_mandatoryrequired
    imaging • used at INITIAL_WORKUP
    Coronary angiography + IVUS mandatory for any NSTEMI in transplant recipient — angio shows diffuse pruning + small-vessel disease + epicardial stenosis (CAV signature); IVUS gold standard for CAV detection (intimal thickness >0.5 mm) per ISHLT staging Mehra PMID 26277690
  • endomyocardial_biopsy_if_rejection_suspected
    imaging • used at BRANCHING_WORKUP
    Gold standard for ACR (ISHLT 2010 PMID 21177015) and AMR (pAMR0-pAMR3 per ISHLT 2013) — perform if concurrent rejection suspected (sub-therapeutic CNI, DSA positivity, restrictive echo pattern, recent biopsy positive)

12-phase flow (12)

  1. 1FRAME
    Heart-transplant recipient with NSTE-ACS pattern — differential dominated by CAV-driven NSTEMI; concurrent rejection (ACR/AMR) possible; classical plaque rupture less common; denervated graft blunts angina (silent ischemia rule); inherits NSTEMI arc from cardio.nstemi.core.v1; treatment paradox vs atherosclerotic NSTEMI: CYP3A4-safe statin + NSAID absolute avoidance + cautious CCB selection + CNI management
    inputs: transplant_date_and_vintage, current_immunosuppression_regimen
    advance: Transplant context + CAV vs rejection vs plaque-rupture framed
  2. 2ENTRY
    Notify transplant cardiology immediately (24/7 line); emergent cath lab activation with mandatory IVUS for CAV substrate confirmation; concurrent biopsy planning if rejection suspected; bedside echo; consider CMV PCR + DSA panel up front
    inputs: age
    actions: acs_pathway
    advance: Transplant team activated + cath lab booked with IVUS
  3. 3CONTEXT
    Transplant vintage, full immunosuppression regimen with troughs, baseline LVEF + LV mass, CAV grade history with prior IVUS measurements, DSA history with C1q, prior rejection episodes, CMV/EBV serology + PCR history, CYP3A4 drug-interaction screen for statins / CCB / antibiotics / antifungals (KDIGO transplant 2009)
    inputs: transplant_date_and_vintage, current_immunosuppression_regimen, prior_cav_grade_and_imaging_history, prior_rejection_episodes_and_dsa_status, cni_trough, creatinine_egfr, cbc
    advance: Transplant context complete
  4. 4RED_FLAGS
    Cardiogenic shock (graft failure SCAI C+ — DanGer Shock PMID 38587234 Impella benefit but consider re-transplant evaluation early); concurrent severe rejection (AMR or 3R ACR) compounding ischemia; opportunistic infection mimic (CMV myocarditis can present like ACS — Hosenpud Lancet 1998); life-threatening arrhythmia in denervated graft (often atypical presentation)
    inputs: sbp, hs_troponin_serial
    actions: cardiogenic_shock, chest_pain
    advance: Red flags screened or escalated
  5. 5INITIAL_WORKUP
    STAT echo + serial hsTn + NT-proBNP + BMP + CBC + CMV/EBV PCR + lactate; CXR; STAT CNI trough + MMF level if available; ECG serial; standard ACS labs; IVUS-guided coronary angiography
    inputs: hs_troponin_serial, nt_probnp, echo_stat, creatinine_egfr, cni_trough, cmv_pcr, cbc, cor_angio_with_ivus_mandatory
    actions: acs_pathway, panel.cardiac, panel.renal, panel.cbc
    advance: Baseline transplant labs + STAT echo + IVUS-coronary angio documented
  6. 6BRANCHING_WORKUP
    IVUS quantifies CAV severity (intimal thickness >0.5 mm per ISHLT staging); cardiac MRI if eGFR ≥30 for ischemia/scar burden (gadolinium safer than iodinated contrast in this population); DSA panel + complement-binding (C1q) DSA + endomyocardial biopsy if concurrent rejection suspected (sub-therapeutic CNI, DSA positivity, restrictive echo); CMV-driven CAV acceleration screen
    inputs: cor_angio_with_ivus_mandatory, dsa_panel_and_c1q, endomyocardial_biopsy_if_rejection_suspected
    advance: CAV substrate documented + concurrent rejection assessed + CMV status known
  7. 7DIFFERENTIAL
    CAV-driven NSTEMI (diffuse small-vessel + epicardial — most common in late transplant) vs CAV focal lesion (PCI-amenable) vs classical plaque-rupture NSTEMI vs concurrent ACR/AMR vs CMV myocarditis vs supply-demand mismatch (anemia, sepsis, hypoxia) vs Takotsubo per ISHLT 2023 + 4th UDMI 2018
    inputs: cor_angio_with_ivus_mandatory
    advance: Substrate identified
  8. 8RISK_STRATIFICATION
    TIMI / HEART for ACS risk (transplant recipients often score in higher bands due to baseline CAV substrate); CAV ISHLT staging (1/2/3 per Mehra PMID 26277690) for graft prognosis; CAV ISHLT 3 + new NSTEMI = re-transplant trigger consideration; concurrent AMR worst prognosis; SCAI staging if shock complicates; AC for AF if detected (DOAC preferred — apixaban/rivaroxaban — but CYP3A4 drug-interaction caution with strong CNI inhibitors)
    inputs: age, sbp, hr, creatinine_egfr, hs_troponin_serial
    actions: calc.heart, calc.cha2ds2vasc, calc.ckd_epi_2021
    advance: Risk band documented + management arm selected
  9. 9TREATMENT
    Standard ACS bundle (ASA + P2Y12 + UFH) per ACC/AHA 2025 — but PCI strategy depends on CAV pattern: focal lesion → IVUS-guided PCI; diffuse CAV → medical management + re-transplant evaluation; CABG rare given diffuse pattern + redo-sternotomy risk. CYP3A4-SAFE STATIN ONLY (pravastatin or pitavastatin per ISHLT 2023 + Kobashigawa NEJM 1995 PMID 7637810) — simvastatin/lovastatin CONTRAINDICATED with CNI. AVOID NSAIDs absolutely (allograft nephrotoxicity + CNI synergistic AKI). CAUTIOUS CCB selection (avoid diltiazem/verapamil with CNI — CYP3A4 toxicity; if BP control needed, prefer amlodipine with close CNI monitoring). β-blocker per standard post-MI but denervated graft adrenergic response uncertain. CONTINUE maintenance immunosuppression — DO NOT HOLD (precipitates rejection). mTOR substitution (sirolimus/everolimus) for CAV per CAVS-1/CRAD discussed with transplant team for chronic management. Concurrent rejection if biopsy ≥2R ACR or pAMR2/3 → pulse methylprednisolone 1g IV × 3d + plasmapheresis + IVIG + rituximab per ISHLT
    inputs: cni_trough, creatinine_egfr, cbc
    advance: Targeted PCI/medical/re-transplant strategy started + concurrent rejection treated if present
  10. 10DISPOSITION
    CICU post-PCI mandatory; transplant program co-management; transplant ward thereafter; never to telemetry only; cardiac surgery on standby if focal CAV not amenable to PCI
    advance: Unit + transplant team co-management activated
  11. 11MONITORING
    Repeat troponin q6h × 24 h; CNI troughs daily during acute period; surveillance biopsy at 2 wk if any rejection suspicion; DSA panel q month × 3 if AMR co-driver; echo at 5-7 d for thrombus + LV recovery; CMV PCR weekly during active CMV viremia; annual CAV imaging (angio + IVUS); BMP daily on AC + post-contrast (KDIGO 2026)
    inputs: hs_troponin_serial, cni_trough, echo_stat, creatinine_egfr
    actions: panel.cardiac, panel.renal
    advance: Post-treatment monitoring plan in place
  12. 12FOLLOWUP
    Transplant cardiology long-term: annual angio + IVUS for CAV; surveillance biopsy per program (decreasing frequency over time); DSA q3-6 mo; mTOR inhibitor (sirolimus / everolimus) substitution for CNI to slow CAV progression per CAVS-1 / CRAD + ISHLT 2024 update strongly considered; CYP3A4-safe statin maintenance (pravastatin/pitavastatin); cardiac rehab phase II per ACC/AHA 2025 (modified intensity); re-transplant listing if CAV ISHLT 3 with non-recoverable graft per ISHLT 2023; vaccination (NO live vaccines); cancer surveillance (skin, PTLD)
    advance: Transplant program plan + mTOR consideration documented + CAV surveillance scheduled