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cardio.acute-hf.checkpoint-inhibitor-cardiotoxicity.v1

Acute HF — Immune checkpoint inhibitor (ICI) cardiotoxicity / fulminant myocarditis

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Phase E variant of cardio.acute-hf.core.v1 — Immune checkpoint inhibitor (ICI)-induced cardiotoxicity / fulminant myocarditis. Distinguished from broader cardio.acute-hf.chemotherapy-induced.v1 by exclusive focus on ICI mechanism (PD-1/PD-L1/CTLA-4 inhibitors: nivolumab, pembrolizumab, ipilimumab, atezolizumab, durvalumab, avelumab, cemiplimab). T-cell-mediated myocarditis with HIGHEST mortality of all irAEs; peak 4-6 wk post-initiation; combination ICI worse than monotherapy. Specializes high-sensitivity troponin (often >100x ULN), cardiac MRI Lake Louise criteria, endomyocardial biopsy as GOLD STANDARD (T-cell lymphocytic infiltrate), CK + LDH for myositis overlap, AV-block + arrhythmia screen, and combined irAE recognition (myositis, myasthenia, hepatitis, thyroiditis). STORM protocol: HIGH-DOSE methylprednisolone 1 g IV daily ×3-5 d EMPIRICALLY (Mahmood JACC 2018 PMID 29420041 — delay = death); IF REFRACTORY at 24-72h → abatacept 10 mg/kg IV q2 weeks (Salem RIVAL PMID 39432268; preferred salvage); add mycophenolate mofetil + IVIG; INFLIXIMAB CONTRAINDICATED for cardiac (TNF-α worsens HF). VA-ECMO bridge for cardiogenic shock; temporary pacing for high-grade AV block. Cancer continuation: ICI rechallenge CONTRAINDICATED after grade 3-4 myocarditis (recurrent myocarditis ≥50% per Power PMID 33779739); shared decision with oncology on alternative non-ICI cancer therapy. Manifest pointer reuses cardio.acute-hf.core.v1 manifest. Design-brief pointer reuses parent (ICI-storm-specific differences documented inline). Status INTEGRATED until terminology + RxNav-validated drug codes are reconciled.

Entry points (4)

  • medication
    Patient on active PD-1/PD-L1/CTLA-4 inhibitor (nivolumab, pembrolizumab, ipilimumab, atezolizumab, durvalumab, avelumab, cemiplimab) presenting with new dyspnea, chest pain, palpitations, or syncope — ICI myocarditis until proven otherwise
    active_ici_therapy_with_new_cardiac_symptoms
  • lab_abnormality
    Any troponin elevation in an ICI patient — STAT cardiology consult; treat empirically with high-dose methylprednisolone while workup proceeds (Mahmood JACC 2018 PMID 29420041 — delay = death)
    troponin_elevation_in_ici_patient
  • imaging
    New high-grade AV block, ventricular arrhythmia, or QRS widening in ICI patient (4-6 wk post-initiation peak) — fulminant ICI myocarditis pattern
    ecg_new_av_block_or_arrhythmia_in_ici_patient
  • symptom
    ICI patient with myocarditis features + concomitant myositis (CK elevation), myasthenia gravis, or hepatitis — combined irAE pattern with worse prognosis
    ici_myocarditis_with_concomitant_irae

Required inputs (13)

  • agerequired
    demographic • used at CONTEXT
    Age informs immunosuppression tolerance + cancer-therapy continuation calculus
  • cancer_diagnosis_and_stagerequired
    history • used at CONTEXT
    Cancer prognosis informs immunosuppression intensity + ICI permanent discontinuation impact
  • specific_ici_agent_and_combination_statusrequired
    medication • used at CONTEXT
    Specific ICI (PD-1 vs PD-L1 vs CTLA-4) + monotherapy vs combination (combination ICI carries higher myocarditis incidence + severity); cycle number; date of last dose
  • troponin_high_sensitivity_serialrequired
    lab • used at INITIAL_WORKUP
    High-sensitivity troponin is the most sensitive ICI myocarditis screen; often markedly elevated (>100x ULN); serial trending guides treatment response (Mahmood JACC 2018 PMID 29420041)
  • ck_total_and_ck_mbrequired
    lab • used at INITIAL_WORKUP
    CK total + CK-MB to detect concomitant myositis (combined irAE; very common in ICI myocarditis); LDH also useful
  • nt_probnprequired
    lab • used at INITIAL_WORKUP
    NT-proBNP elevation suggests cardiac strain; baseline + serial for response tracking
  • creatininerequired
    lab • used at CONTEXT
    eGFR for cardiac MRI gadolinium dosing + ACEi/ARB/ARNI dosing + immunosuppression considerations
  • ecg_with_block_and_arrhythmia_screenrequired
    imaging • used at INITIAL_WORKUP
    ECG: new AV block (1st/2nd/3rd-degree), QRS widening, ventricular ectopy, or new ventricular arrhythmia — characteristic and ominous in ICI myocarditis
  • echo_with_lvef_and_strainrequired
    imaging • used at INITIAL_WORKUP
    Echo for LVEF + GLS strain + RV function; LVEF may be preserved early in ICI myocarditis (troponin precedes LVEF drop)
  • cardiac_mri_lake_louise_criteria
    imaging • used at BRANCHING_WORKUP
    Cardiac MRI with T1/T2 mapping + LGE per Lake Louise criteria — high diagnostic yield for ICI myocarditis when EMB not feasible
  • endomyocardial_biopsy_emb
    imaging • used at BRANCHING_WORKUP
    EMB is the GOLD STANDARD: T-cell-predominant lymphocytic infiltrate confirms ICI myocarditis; reserve for life-threatening cases or diagnostic uncertainty after MRI
  • concomitant_irae_screening_myositis_myasthenia_hepatitis
    history • used at INITIAL_WORKUP
    Concomitant myositis, myasthenia gravis, hepatitis, or thyroiditis often co-occurs with ICI myocarditis; combined irAE pattern significantly worsens prognosis
  • sbprequired
    vital • used at RED_FLAGS
    SBP guides shock recognition + immunosuppression adjuncts + MCS decision

12-phase flow (10)

  1. 1FRAME
    ICI cardiotoxicity = T-cell-mediated myocarditis from PD-1/PD-L1/CTLA-4 inhibitor; HIGHEST mortality of all irAEs; peak 4-6 wk post-initiation; combination ICI worse than monotherapy; treat empirically with high-dose steroid while workup proceeds (delay = death)
    inputs: specific_ici_agent_and_combination_status, troponin_high_sensitivity_serial
    advance: ICI cardiotoxicity suspicion confirmed
  2. 2ENTRY
    STAT cardiology + cardio-oncology activation; bedside ECG + echo; high-sensitivity troponin; empiric high-dose methylprednisolone 1 g IV started in parallel with workup if any troponin elevation in ICI patient
    inputs: age, cancer_diagnosis_and_stage
    advance: cardio-oncology team activated + empiric steroid considered
  3. 3CONTEXT
    Cancer diagnosis + stage + ICI agent (PD-1/PD-L1/CTLA-4) + monotherapy vs combination + cycle # + last-dose date + prior irAE history + concomitant immunosuppressive use
    inputs: creatinine
    advance: oncologic + immunologic context complete
  4. 4RED_FLAGS
    Fulminant ICI myocarditis: cardiogenic shock, high-grade AV block, sustained VT/VF, refractory arrhythmia; combined irAE with grade 4 features (myasthenic crisis, hepatic failure)
    inputs: sbp, troponin_high_sensitivity_serial
    actions: cardiogenic_shock
    advance: red flags screened + storm-protocol activated if applicable
  5. 5INITIAL_WORKUP
    High-sensitivity troponin (often >100x ULN), CK + CK-MB, LDH, NT-proBNP, BMP, CBC, lactate, LFTs (rule out hepatitis irAE), TSH (rule out thyroiditis irAE), ECG (AV block + QRS widening), CXR, bedside echo with strain; START empiric methylprednisolone 1 g IV daily WITHIN 24h of suspicion
    inputs: troponin_high_sensitivity_serial, ck_total_and_ck_mb, nt_probnp, ecg_with_block_and_arrhythmia_screen, echo_with_lvef_and_strain
    actions: acute_pulm_edema, panel.cardiac, panel.renal
    advance: workup documented + empiric immunosuppression initiated
  6. 6BRANCHING_WORKUP
    Cardiac MRI with Lake Louise criteria (T1/T2 mapping + LGE) within 48-72h; endomyocardial biopsy decision at 48-72h if life-threatening or diagnostic uncertainty (T-cell lymphocytic infiltrate confirms ICI myocarditis); concomitant irAE workup (CK, AST/ALT, glucose, TSH, ACh-receptor antibodies); rule out ischemic ACS confounder if chest pain dominant
    inputs: cardiac_mri_lake_louise_criteria
    actions: acs_pathway
    advance: differential narrowed + biopsy decision made + combined irAE characterized
  7. 7TREATMENT
    STORM PROTOCOL: HIGH-DOSE methylprednisolone 1 g IV daily ×3-5 d → prednisone 1 mg/kg PO with slow taper over 4-6 weeks. IF REFRACTORY at 24-72h (persistent troponin or LVEF drop): ADD abatacept 10 mg/kg IV (CTLA-4 Ig per Salem RIVAL PMID 39432268; preferred salvage) and/or mycophenolate mofetil 1 g BID; IVIG 2 g/kg over 2-5 d as adjunct. INFLIXIMAB CONTRAINDICATED — TNF-α inhibitor worsens cardiac HF. STANDARD ADHF: IV diuretic for pulmonary edema; norepinephrine for shock; AVOID negative inotropes if possible. CONDUCTION: temporary transvenous pacing for high-grade block; permanent if irreversible. SHOCK: VA-ECMO bridge if cardiogenic shock refractory to medical + steroid. HOLD ICI PERMANENTLY for grade ≥3 myocarditis. GDMT 4-pillar started once stable.
    inputs: sbp
    actions: protocol.cardiogenic_shock
    advance: storm regimen active + cancer-therapy permanent-hold decision documented
  8. 8DISPOSITION
    CICU for fulminant ICI myocarditis (block, shock, refractory storm); cardiology floor only if mild and steroid-responsive; transfer to advanced HF / transplant center if MCS-dependent or refractory
    advance: unit assigned + multidisciplinary plan documented
  9. 9MONITORING
    Continuous telemetry with pacer pads (block + VT/VF surveillance), serial troponin q6h until trending down, daily NT-proBNP, daily echo, daily BMP, daily LFTs (steroid + concomitant hepatitis irAE), daily glucose (steroid hyperglycemia), repeat MRI at 6 weeks for response if EMB not done
    inputs: troponin_high_sensitivity_serial, nt_probnp
    actions: panel.cardiac
    advance: monitoring + storm-response surveillance plan booked
  10. 10FOLLOWUP
    Cardio-oncology clinic at 2 weeks, 6 weeks, 3 months, 6 months, 12 months; serial troponin + echo + MRI for surveillance; permanent ICI hold (rechallenge contraindicated per Power PMID 33779739); shared decision on alternative non-ICI cancer therapy with oncology; ICD evaluation if persistent LVEF <35% on full GDMT; long-term steroid taper monitoring
    advance: cardio-oncology + permanent ICI-hold + alternative-therapy + survivorship plan documented