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cardio.post-arrest.cpvt-channelopathy.v1

Post-cardiac-arrest care — CPVT channelopathy (RYR2 / CASQ2; exercise- or emotion-triggered bidirectional VT → VF arrest)

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Phase E variant of cardio.post-arrest.core.v1 — narrowed to catecholaminergic polymorphic ventricular tachycardia (CPVT) channelopathy as the etiology of the index out-of-hospital VF arrest. Primary genotypes: RYR2 autosomal dominant (~55-65% of clinically diagnosed CPVT — gain-of-function leak of Ca²⁺ from sarcoplasmic reticulum during diastole → delayed afterdepolarizations → bidirectional VT) and CASQ2 autosomal recessive (~3-5% — loss of SR Ca²⁺ buffering); rarer mutations include CALM1/2/3, KCNJ2 (Andersen-Tawil overlap), TRDN, TECRL. Per HRS 2017 PMID 28219760. Sister to cardio.post-arrest.long-qt-channelopathy.v1 (also a channelopathy, but ACTION-POTENTIAL-BASED — KCNQ1/KCNH2/SCN5A — with prolonged QTc on resting ECG vs CPVT which is CALCIUM-HANDLING with normal resting ECG and exercise-provoked bidirectional VT) and cardio.post-arrest.brugada-channelopathy.v1 (sodium-channel channelopathy with Type 1 V1-V3 pattern; sleep / fever trigger). THIS dossier covers POST-ROSC care of the CPVT-arrest cohort with focus on EXERCISE STRESS ECG (gold standard, NOT resting ECG which is normal in CPVT), genetic panel (RYR2/CASQ2 core; expanded if needed), cascade family screening with EXERCISE STRESS TEST (highest yield), nadolol 1.5-2.0 mg/kg/d (preferred over propranolol or metoprolol per Roston/Mazzanti registry meta-analysis), flecainide 100-300 mg/d adjunct (van der Werf JACC 2011 + RyR2 mechanism Watanabe Nat Med 2009 — HRS 2017 IIa), LCSD for refractory CPVT or β-blocker intolerance (HRS 2017 IIa — most effective non-pharm intervention), ICD per HRS 2017 Class I (sustained VT/VF survivor) with LONG DETECTION + ATP-FIRST + HIGH THERAPY THRESHOLD programming (avoid shock-storm catecholamine surge), and lifelong avoidance of competitive sports + catecholaminergic substances. Critical post-ROSC pharmacologic AVOIDS (signature departure from generic post-arrest care): ISOPROTERENOL (CONTRAINDICATED — direct β-1 catecholamine triggers RyR2 leak; opposite of Brugada where iso is first-line); EPINEPHRINE chronic infusion (catecholamine surge is THE trigger — minimize to ACLS arrest dose only); DOBUTAMINE (substitute milrinone — non-catecholamine PDE3 inotrope); HIGH-DOSE NOREPINEPHRINE (substitute vasopressin or low-dose phenylephrine when feasible); SYMPATHOMIMETIC DECONGESTANTS (pseudoephedrine); ADHD STIMULANTS (methylphenidate, dextroamphetamine — substitute non-stimulant atomoxetine if treatment needed); COCAINE / AMPHETAMINES / MDMA lifelong; HIGH-DOSE CAFFEINE / ENERGY DRINKS (counsel limitation); shivering during TTM rewarm = catecholamine surge → aggressive control with magnesium + acetaminophen + buspirone + adequate sedation. Exercise stress ECG (treadmill or bicycle) at inherited-arrhythmia center (continuous ECG + defibrillator pads + EP supervision) is the diagnostic gold standard — reproduces bidirectional or polymorphic VT in ~75% of true CPVT cases even when resting ECG is normal; performed POST-STABILIZATION not during acute admission; cascade screening of relatives uses exercise stress test (resting ECG normal so will miss carriers). ICD programming critical CPVT-specific consideration: ICD shocks themselves trigger catecholamine surge that can PROVOKE further VT/VF (so-called "shock-storm"); program with long detection windows + ATP-first + high therapy thresholds; ICD WITHOUT optimal nadolol + flecainide ± LCSD is INADEQUATE alone in CPVT. Inherits manifest + design-brief pointer from parent cardio.post-arrest.core.v1; specializes the exercise-stress ECG provocation + channelopathy workup + family screening + nadolol + flecainide adjunct + LCSD + ICD + competitive-sports avoidance arcs. 5 setting playbooks (ed, icu, inpatient, transition, outpatient). 6 severity triggers: recurrent bidirectional/polymorphic VT storm-bridge, inadvertent catecholamine administered post-ROSC (common nursing handoff failure mode — especially isoproterenol confused as a generic post-arrest agent), shivering during TTM rewarm as CPVT trigger, ICD eligibility evaluation with CPVT-specific programming caution, cascade family screening with EXERCISE STRESS TEST referral, LCSD evaluation for refractory CPVT. 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)

  • symptom
    ROSC after out-of-hospital VF arrest with known CPVT (prior diagnosis, prior exercise-triggered syncope, family history) or with sentinel pre-arrest narrative — exertion- or emotion-triggered collapse in a young patient with normal resting ECG and structurally normal heart on echo
    rosc_after_oohca_with_known_or_suspected_cpvt
  • history
    Witnessed arrest during exercise (running, swimming, sports) or intense emotion (fright, anger, surprise) in a previously healthy young patient (childhood–young adulthood) with normal resting 12-lead ECG and normal echo — high CPVT pretest probability; classic phenotype
    witnessed_exercise_or_emotion_triggered_arrest_in_young_patient_normal_resting_ecg
  • history
    Family history of sudden death <40 y, known CPVT in first-degree relative, or familial pattern of exercise-triggered syncope — autosomal dominant RYR2 most common (~55-65%); offer genetic panel + cascade screening with EXERCISE STRESS TEST (highest yield)
    family_history_sudden_death_under_40_or_known_cpvt_or_exercise_syncope
  • history
    Prior unexplained exercise- or emotion-triggered syncope (vs vasovagal pre-syncope which is provoked by upright posture / pain / heat — distinct mechanism) — strong pretest probability for CPVT; missed-opportunity diagnosis
    prior_unexplained_exercise_or_emotion_triggered_syncope_pre_arrest
  • imaging
    Documented bidirectional VT (alternating QRS axis ~180° beat-to-beat — pathognomonic for CPVT) or polymorphic VT on rhythm strip during pre-arrest event or resuscitation — high specificity for CPVT (also seen in digoxin toxicity and Andersen-Tawil)
    bidirectional_or_polymorphic_vt_documented_pre_arrest_or_during_resuscitation
  • lab_abnormality
    Normal resting QTc + normal resting ECG + normal echo paired with exercise-triggered arrest phenotype — actively rules OUT LQT (prolonged QTc) and structural causes (HCM/ARVC); points TOWARD CPVT vs idiopathic VF; sets up exercise-stress ECG provocation as next diagnostic step
    normal_qtc_normal_resting_ecg_normal_echo_with_exercise_triggered_arrest_phenotype

Required inputs (25)

  • agerequired
    demographic • used at CONTEXT
    CPVT typically manifests in childhood / adolescence / young adulthood (median age first event ~10–14 y; ~80% by age 40); pediatric resuscitation modifications below age 8; ICD device-size considerations in pediatric / small-frame patients; nadolol weight-based dosing 1.5–2.0 mg/kg/d
  • sexrequired
    demographic • used at CONTEXT
    Equal sex distribution unlike Brugada (8:1 male) or LQT2 (female event predominance); informs cascade-screening prioritization
  • witnessed_arrest_with_exercise_or_emotion_triggerrequired
    history • used at CONTEXT
    Trigger pattern is highly informative and pathognomonic — exertion (running, swimming, competitive sports) or intense emotion (fright, surprise, anger) is the CPVT signature; informs lifelong sports-avoidance + emotion-trigger management; drives genetic panel + exercise-stress ECG referral
  • time_to_cpr_minrequired
    history • used at CONTEXT
    CPR within 1 min dramatically improves outcome; CAHP/OHCA score input
  • time_to_aed_defibrillation_minrequired
    history • used at CONTEXT
    AED within 3 min → 50%+ survival; venue AED program (school, gym, sports field) presence is dominant prognostic factor + suggests sports / exertion trigger context
  • initial_rhythmrequired
    history • used at CONTEXT
    VF most common terminal rhythm (~85–90%); bidirectional or polymorphic VT degenerating to VF is the classic CPVT mechanism; informs storm-suppression bridge planning
  • family_history_sudden_death_or_known_cpvt_or_exercise_syncoperequired
    history • used at CONTEXT
    Family history of SCD <40 y, known CPVT (autosomal dominant RYR2 in ~55-65%; recessive CASQ2 in ~3-5%), or familial pattern of exercise-triggered syncope is critical input — drives cascade exercise-stress ECG screening of relatives + genetic referral
  • prior_exercise_or_emotion_triggered_syncoperequired
    history • used at CONTEXT
    Prior exercise- or emotion-triggered syncope is a classic missed-opportunity diagnosis for CPVT (often misattributed to vasovagal); strong pretest probability marker
  • pre_arrest_medication_list_catecholamine_surge_auditrequired
    history • used at CONTEXT
    Comprehensive medication review for sympathomimetics (decongestants pseudoephedrine), amphetamines (ADHD stimulants methylphenidate / dextroamphetamine), illicit substances (cocaine, MDMA), high-dose caffeine — STOP all offenders + document; informs whether surge unmasked CPVT substrate
  • sbprequired
    vital • used at TREATMENT
    MAP ≥65 target post-ROSC; SCAI staging if shock; CAUTIOUS vasopressor in CPVT — minimize epinephrine + NE because catecholamine surge is THE trigger; vasopressin or low-dose phenylephrine preferred substitute when feasible
  • hrrequired
    vital • used at TREATMENT
    Bradycardia is NOT a CPVT trigger (unlike LQT3) — DO NOT use isoproterenol (catecholamine — directly triggers RyR2 leak); pacing for symptomatic bradycardia per standard ACLS
  • core_temprequired
    vital • used at TREATMENT
    TTM target 33–37.5 °C × 24 h (TTM2 PMID 34133859); shivering during rewarm is a catecholamine surge trigger — aggressive shivering control with magnesium + acetaminophen + buspirone + adequate sedation
  • spo2required
    vital • used at TREATMENT
    Avoid hyperoxia: SpO2 92–98% (AHA 2020 Class IIa)
  • ecg_12_lead_serial_with_qtc_and_baseline_documentationrequired
    imaging • used at INITIAL_WORKUP
    Resting ECG is typically NORMAL in CPVT (no QT prolongation, no V1-V3 coved ST, no epsilon waves) — this normalcy is itself diagnostic when paired with exercise-trigger phenotype; serial ECGs document QTc + baseline morphology before exercise stress provocation
  • tte_high_resolutionrequired
    imaging • used at INITIAL_WORKUP
    Rule out structural disease (ARVC most important differential — RV-dominant cardiomyopathy can present with exertion-triggered VT; HCM, anomalous coronary, infiltrative); CPVT heart is structurally normal — structural finding triggers alternate or overlap pathway
  • cardiac_mri_at_4_to_6_wk
    imaging • used at FOLLOWUP
    Cardiac MRI at 4–6 wk post-arrest if echo equivocal — RULE OUT ARVC overlap (key differential — exertion-triggered VT in young patient overlaps phenotypically), HCM, infiltrative; allows post-arrest stunning to resolve before assessment
  • exercise_stress_ecg_at_inherited_arrhythmia_center_post_stabilizationrequired
    imaging • used at FOLLOWUP
    EXERCISE STRESS ECG (treadmill or bicycle) > resting ECG > epinephrine challenge for CPVT diagnosis; reproduces bidirectional or polymorphic VT in ~75% of true CPVT cases even with normal resting ECG; performed in inherited-arrhythmia center with continuous ECG + defibrillator pads + EP supervision; cascade screening of relatives also uses exercise stress test
  • troponinrequired
    lab • used at INITIAL_WORKUP
    Often modestly elevated from arrest + CPR; rise pattern helps differentiate from ACS-mediated arrest; primary CPVT arrest typically negative or modest
  • lactaterequired
    lab • used at INITIAL_WORKUP
    Tissue hypoperfusion + post-arrest perfusion debt; clearance trajectory drives prognosis (SCAI 2022 PMID 35718438; CardShock PMID 26333869)
  • creatininerequired
    lab • used at CONTEXT
    eGFR for nadolol dose adjustment (renally cleared — half-life prolonged in CKD; reduce dose if eGFR <50)
  • potassiumrequired
    lab • used at INITIAL_WORKUP
    K target ≥4.0 supportive; hypokalemia not the dominant CPVT trigger (vs LQT) but still avoided
  • magnesiumrequired
    lab • used at INITIAL_WORKUP
    Mg target ≥2.0 supportive; replace standard polymorphic VT supportive therapy + shivering suppression during rewarm
  • tox_screen_for_cocaine_amphetamine_mdma
    lab • used at CONTEXT
    Sympathomimetic / catecholaminergic substances are direct CPVT triggers; tox screen at presentation informs acquired vs unmasked CPVT phenotype + lifestyle counseling
  • genetic_panel_ryr2_casq2_expandedrequired
    lab • used at FOLLOWUP
    Targeted gene panel — RYR2 core (~55–65% positive), CASQ2 (~3–5% recessive), expanded panel CALM1/2/3, KCNJ2, TRDN, TECRL if family history positive or phenotype atypical; informs prognosis + cascade testing of relatives at proband mutation; per HRS 2017 PMID 28219760
  • cxr_post_cprrequired
    imaging • used at INITIAL_WORKUP
    Rib fractures from CPR; pneumothorax; aspiration; baseline for ICD lead placement planning

12-phase flow (12)

  1. 1FRAME
    Recognize post-ROSC + exercise- or emotion-triggered arrest in young patient + normal resting ECG + structurally normal heart as CPVT-arrest cohort; pivot from generic post-arrest care to channelopathy-specific avoidance protocol; route to parent cardio.post-arrest.core.v1 for TTM + neuroprog while specializing on exercise-stress ECG provocation + family screening + nadolol + flecainide adjunct + LCSD + ICD + competitive-sports avoidance arcs
    inputs: witnessed_arrest_with_exercise_or_emotion_trigger, ecg_12_lead_serial_with_qtc_and_baseline_documentation, tte_high_resolution
    advance: CPVT high pretest probability confirmed + structural disease screen initiated
  2. 2ENTRY
    Standard ACLS for index arrest; immediate scene CPR + AED deployment; transport to PCI-capable + EP-capable facility; activate EP + inherited-arrhythmia center early; STOP all sympathomimetic / catecholaminergic agents from pre-arrest medication list (decongestants, ADHD stimulants, illicit substances)
    inputs: age, time_to_cpr_min, time_to_aed_defibrillation_min, pre_arrest_medication_list_catecholamine_surge_audit
    advance: ACLS + AED + transport + EP team activation + sympathomimetic drug audit initiated
  3. 3CONTEXT
    Trigger pattern (exertion / emotion is pathognomonic — running, swimming, competitive sports, fright, anger, surprise); time-to-CPR; time-to-AED; initial rhythm (VF most common — ~85–90%); family history of SCD <40 y, known CPVT, or familial exercise-triggered syncope; prior exercise- or emotion-triggered syncope (commonly missed); comprehensive pre-arrest sympathomimetic + caffeine audit
    inputs: sex, initial_rhythm, family_history_sudden_death_or_known_cpvt_or_exercise_syncope, prior_exercise_or_emotion_triggered_syncope, sbp, hr, core_temp, spo2, creatinine, tox_screen_for_cocaine_amphetamine_mdma
    advance: context + family history + sympathomimetic drug audit + trigger pattern documented
  4. 4RED_FLAGS
    Recurrent VT/VF post-ROSC suggests ongoing storm physiology (route to EP for storm management); inadvertent administration of catecholamine post-ROSC (epinephrine drip, isoproterenol, dobutamine) → STOP + substitute vasopressin / phenylephrine / milrinone; shivering during TTM rewarm = catecholamine surge → aggressive sedation + magnesium + buspirone + acetaminophen
    inputs: sbp, hr, core_temp
    actions: cardiogenic_shock, wide_complex_tach
    advance: red flags screened + storm-bridge route decided + catecholaminergic drugs cleared from active orders + shivering control protocol initiated
  5. 5INITIAL_WORKUP
    Serial 12-lead ECG (typically normal in CPVT — this normalcy is itself diagnostic when paired with exercise-trigger phenotype); STAT echo (rule out structural disease — CPVT heart is normal; ARVC is key differential); troponin (rule out ischemic mimic); BMP + Mg + Ca; CBC; ABG; CXR; tox screen for sympathomimetics; comprehensive medication audit
    inputs: ecg_12_lead_serial_with_qtc_and_baseline_documentation, tte_high_resolution, troponin, lactate, potassium, magnesium, cxr_post_cpr
    actions: post_arrest_care, panel.cardiac, panel.renal
    advance: workup complete + CPVT pretest probability refined + structural / ischemic causes excluded + electrolytes optimized
  6. 6BRANCHING_WORKUP
    Genetic panel referral (RYR2 core; CASQ2 recessive; expanded CALM1/2/3, KCNJ2, TRDN, TECRL if family history positive); EP consult for ICD planning (sustained VT/VF survivor = HRS 2017 Class I); STEMI on post-ROSC ECG (extremely rare in primary CPVT) → cath; recurrent VF storm → urgent EP for storm management + LCSD bridge; EXERCISE STRESS ECG SCHEDULED at inherited-arrhythmia center post-stabilization (NOT during acute admission — performed once stable); cascade-screening referral for relatives includes exercise stress test
    actions: acs_pathway, wide_complex_tach
    advance: branching decisions made + genetic referral placed + exercise stress test scheduled + EP plan documented
  7. 7DIFFERENTIAL
    CPVT (RYR2 / CASQ2 — exercise- or emotion-triggered bidirectional VT in young patient with normal resting ECG and structurally normal heart) vs ARVC (RV-dominant CMP with epsilon waves and structural changes on cardiac MRI — key differential for exertion-triggered VT in young) vs LQT (prolonged QTc on resting ECG — different channelopathy mechanism) vs Brugada (V1-V3 coved ST + sleep / fever trigger — different channelopathy) vs digoxin toxicity (bidirectional VT with elevated digoxin level + clinical context — non-channelopathic mimic) vs Andersen-Tawil syndrome (KCNJ2 — periodic paralysis + dysmorphic features + bidirectional VT overlap) vs idiopathic VF — this differential drives long-term plan + family screening
    inputs: family_history_sudden_death_or_known_cpvt_or_exercise_syncope, witnessed_arrest_with_exercise_or_emotion_trigger, prior_exercise_or_emotion_triggered_syncope
    advance: CPVT vs ARVC vs LQT vs alternative classification + exercise stress test plan + genetic plan documented
  8. 8RISK_STRATIFICATION
    CAHP/OHCA scores apply (witnessed + bystander CPR + low-flow time + initial rhythm); SCAI shock stage if hemodynamic instability; HEART score not directly applicable (CPVT cohort low ACS pretest); HRS 2017 ICD class — sustained VT/VF survivor = Class I (this population by definition meets ICD criteria); refractoriness to nadolol + flecainide flag if recurrent VT/VF on therapy → escalate to LCSD
    inputs: initial_rhythm, time_to_cpr_min, time_to_aed_defibrillation_min, sbp, lactate
    actions: calc.map, calc.sofa, calc.ckd_epi_2021, calc.cha2ds2vasc, calc.heart
    advance: risk class + ICD eligibility + structural workup status documented
  9. 9TREATMENT
    Standard post-ROSC bundle (CAUTIOUS vasopressor → MAP ≥65 with vasopressin or low-dose phenylephrine substitute when feasible; minimize epinephrine + NE; lung-protective vent; sedation; TTM 33–37.5 °C × 24 h with aggressive shivering control). STOP all sympathomimetic / catecholaminergic agents; AVOID isoproterenol (CONTRAINDICATED — direct β-1 catecholamine triggers RyR2 leak); AVOID dobutamine acute infusion (substitute milrinone for inotropic support if needed). LONG-TERM (initiate before discharge): NADOLOL 1.5–2.0 mg/kg/d PO daily (preferred over propranolol or metoprolol per CPVT registry meta-analysis) once storm controlled; FLECAINIDE 100–300 mg/d PO ADJUNCT to nadolol (van der Werf JACC 2011; HRS 2017 IIa — RyR2 + Na channel dual-blockade); ICD per HRS 2017 Class I (sustained VT/VF survivor) — program with long detection windows + ATP-first + high therapy thresholds (ICD shocks themselves trigger catecholamine surge → shock-storm); LCSD evaluation for refractory CPVT or β-blocker intolerance
    inputs: sbp, hr, core_temp, spo2, creatinine, potassium, magnesium
    actions: protocol.cardiogenic_shock
    advance: post-ROSC bundle + catecholaminergic substitution + shivering control + drug-avoidance protocol + long-term nadolol + flecainide adjunct + ICD pathway documented
  10. 10DISPOSITION
    CICU at EP-capable + inherited-arrhythmia-capable center for cardiac surveillance + ICD planning; transfer to inherited-arrhythmia + LCSD-capable center for refractory CPVT or pediatric / complex genotype
    advance: unit + service-line ownership assigned + EP follow-up booked + LCSD-center transfer planned if refractory
  11. 11MONITORING
    Continuous telemetry × 48–72 h with bidirectional / polymorphic VT surveillance; A-line; multimodal neuroprog ≥72 h post-rewarm (Sandroni 2021 PMID 33745427); aggressive shivering suppression during TTM rewarm; serial ECG q4–6 h × 24 h then q6–8 h × 48 h documenting baseline normalcy; daily medication audit for sympathomimetics; nadolol initiation logging once storm controlled
    inputs: ecg_12_lead_serial_with_qtc_and_baseline_documentation, core_temp
    actions: panel.cardiac, panel.renal
    advance: monitoring + neuroprog + shivering control + drug audit cadence + nadolol titration documented
  12. 12FOLLOWUP
    Cardiology + EP / inherited-arrhythmia clinic at 2–4 wks; cardiac MRI at 4–6 wk (rule out ARVC overlap; allow post-stunning resolution); EXERCISE STRESS ECG at inherited-arrhythmia center post-stabilization (treadmill or bicycle with continuous ECG + defibrillator pads + EP supervision — diagnostic gold standard for CPVT, ~75% sensitivity even with normal resting ECG); GENETIC PANEL completed (RYR2/CASQ2 core; expanded if needed); CASCADE FAMILY SCREENING — first-degree relatives ECG + EXERCISE STRESS TEST (highest yield) + genotyping at proband mutation; nadolol maintenance + flecainide adjunct; ICD interrogation q3–6 mo; LCSD evaluation for refractory CPVT or β-blocker intolerance; LIFELONG AVOIDANCE of competitive sports (HRS 2017 Class I); recreational low-intensity activity titrated to symptoms; emotion / stress trigger management; lifelong avoidance of sympathomimetics + amphetamines + cocaine + MDMA + high-dose caffeine; medic-alert bracelet "CPVT — AVOID catecholamines + competitive sports"; PTSD / mental health screen
    inputs: cardiac_mri_at_4_to_6_wk, exercise_stress_ecg_at_inherited_arrhythmia_center_post_stabilization, genetic_panel_ryr2_casq2_expanded
    advance: cardiology + EP follow-up + exercise stress ECG + genetic panel + cascade family screening + ICD + nadolol + flecainide adjunct + LCSD evaluation + competitive-sports avoidance + lifestyle modifications + mental health all booked / documented