293.3 🏥 內科專科考前版

293.3.1 Mechanistic Deep Dive

293.3.1.1 Anthracycline Mechanism

  • Topoisomerase IIβ in cardiomyocytes (vs IIα in tumor)
  • Mitochondrial damage → ROS
  • DNA damage in cardiomyocytes
  • Apoptosis + necrosis
  • Dexrazoxane: iron chelation + topo IIβ binding

293.3.1.2 ICI Myocarditis Pathobiology

  • T-cell infiltration (mostly CD8+)
  • Loss of self-tolerance
  • Cross-reactivity with cardiac antigens
  • Genetic factors (HLA association)
  • Combination ICI ↑ risk

293.3.1.3 Radiation Pathology

  • Endothelial damage
  • Microvascular injury
  • Fibrosis (myocardial, valvular, pericardial)
  • Accelerated atherosclerosis

293.3.2 Recent Trials & Updates

293.3.2.1 PRADA (2018, 2024 long-term)

  • Candesartan + metoprolol for adjuvant anthracycline in breast cancer
  • Long-term LV preservation
  • Currently Class IIa for prevention

293.3.2.2 MANTICORE 101 Breast (2016)

  • Perindopril or bisoprolol vs placebo for trastuzumab
  • LVEF preservation
  • Class IIa for high-risk

293.3.2.3 OVERCOME (2013)

  • Enalapril + carvedilol in hematologic malignancy
  • Reduced cardiotoxicity

293.3.2.4 STOP-CA (2023) — Atorvastatin

  • Atorvastatin 40 mg vs placebo in anthracycline patients
  • ↓ LVEF decline
  • Class IIa emerging

293.3.2.5 PROACT (2024) — Enalapril

  • Enalapril for anthracycline-induced cardiotoxicity prevention
  • Modest benefit

293.3.2.6 SGLT2i in Cardio-Oncology

  • Empagliflozin, dapagliflozin in cancer-associated HF
  • Emerging benefit

293.3.2.7 EMPA-DOX (Ongoing)

  • Empagliflozin during anthracycline

293.3.3 High-Yield Specialist Points

293.3.3.1 Cardiac MRI in Cardio-Oncology

  • Most sensitive for myocarditis (ICI)
  • Quantifies subclinical injury
  • Distinguishes ICI vs other cardiotoxicity
  • T1/T2 mapping, LGE

293.3.3.2 Strain Imaging (GLS)

  • Subclinical LV dysfunction marker

  • 15% relative reduction = concerning

  • Earlier than LVEF drop

293.3.3.3 Endomyocardial Biopsy

  • Gold standard for ICI myocarditis
  • T-cell infiltrate, necrosis
  • Helps distinguish from other myocarditis

293.3.3.4 ICI Myocarditis Treatment Pearls

  • Steroid pulse: methylpred 1 g/d × 3-5 d → 1 mg/kg taper
  • Refractory: infliximab, MMF, abatacept, ATG
  • JAK inhibitors (tofacitinib) for severe
  • IVIG, plasmapheresis adjunctive
  • ECMO if refractory shock

293.3.3.5 Ponatinib Risk Management

  • Dose reduction (15 mg vs 45 mg)
  • Strict CV risk control
  • Aspirin
  • Statin
  • Smoking cessation

293.3.3.6 Ibrutinib + AF

  • 10-15% incidence over 5 years
  • DOAC compatible
  • HAS-BLED + CHA₂DS₂-VASc weighed
  • May continue ibrutinib + AC if mild

293.3.3.7 Cancer-Associated VTE

  • DOAC preferred (apixaban, edoxaban — Caravaggio, Hokusai-Cancer)
  • LMWH for GI/GU cancer (bleeding risk)
  • Indefinite while cancer active
  • Reduced dose after 6 months consideration

293.3.3.8 Pediatric Cancer Survivors

  • Childhood Cancer Survivor Study (CCSS)
  • 5-15x ↑ CV death
  • Structured surveillance per COG (Children’s Oncology Group)
  • Lifelong cardiology follow-up

293.3.3.9 Pregnancy in Anthracycline Survivors

  • 30% PPCM if anthracycline-exposed
  • Pre-pregnancy echo + counseling
  • Plan delivery, postpartum monitoring

293.3.3.10 Telecardio-oncology

  • Remote monitoring with wearables, virtual visits
  • Improving access to cardio-oncology specialists

293.3.4 Pearls

  • Anthracycline: dose-dependent HF; dexrazoxane + liposomal less toxic
  • Trastuzumab: reversible LV dysfunction; serial echo every 3 mo
  • ICI myocarditis: 0.5-1.5% but 50% mortality; stop + high-dose steroid + immunomodulator
  • BCR-ABL TKI (ponatinib): arterial thrombosis (~ 30%); ASA + aggressive RF control
  • Ibrutinib: AF + bleeding; DOAC compatible
  • 5-FU: vasospasm → MI; stop, nitrate/CCB
  • Radiation: late effects (years); CAD + valve + conduction; lifelong surveillance
  • STOP-CA, PRADA, MANTICORE, PROACT: cardio-protection trials emerging