293.1 🎓 醫孞生版

293.1.0.1 📌 䞀頁重點

293.1.0.1.1 Overview
293.1.0.1.1.1 Definition
  • Cancer Therapy-Related Cardiovascular Toxicity (CTR-CVT): adverse CV effects of cancer treatments (chemotherapy, targeted therapy, immunotherapy, radiation)
293.1.0.1.1.2 Scope
  • LV dysfunction / HF
  • Hypertension
  • Coronary artery disease, ACS
  • Pericardial disease (effusion, tamponade, constrictive)
  • Valvular disease (radiation-induced)
  • Arrhythmias (QT prolongation, AF, ventricular)
  • Vascular toxicity (thromboembolism, dissection)
  • Pulmonary HTN
293.1.0.1.1.3 Patient Population
  • Cancer survivors > 17 million in US
  • Most common cause of non-cancer death in survivors: CVD
  • Childhood cancer survivors: 5-15x ↑ CV death
293.1.0.1.2 Specific Toxicities by Agent Class
293.1.0.1.2.1 Anthracyclines (Doxorubicin, Daunorubicin, Epirubicin, Idarubicin)

Mechanism: oxidative stress, topoisomerase IIβ inhibition, mitochondrial damage

Dose-Dependent Cardiotoxicity: - Doxorubicin: > 250-350 mg/m² cumulative → ↑ HF risk - Older threshold 550 mg/m² (less safe) - Liposomal form less cardiotoxic

Time Course: - Acute (< 1 week): rare, arrhythmia - Early-onset chronic (within 1 yr): more common - Late-onset (years later): childhood cancer survivors

Clinical: - Asymptomatic LV dysfunction → HF - Mostly HFrEF - Often irreversible (vs trastuzumab)

Risk Factors: - Cumulative dose - Age extremes - Pre-existing CV disease - Combination with trastuzumab, radiation - Concomitant cardiotoxic agents

Prevention: - Dexrazoxane: iron chelator, ↓ cardiotoxicity (Class IIa for high-risk + > 300 mg/m²) - Cardiac risk assessment - Lower-dose regimens - Liposomal formulation - ARNI/ACEi + β-blocker + SGLT2i (primary prevention emerging)

Monitoring: - Echo + troponin baseline + during + after treatment - 6-12 months post-completion - Annual surveillance for high-risk

293.1.0.1.2.2 Trastuzumab + Pertuzumab (HER2 Inhibitors)

Mechanism: blocks HER2 → impairs cardiomyocyte repair

Cardiotoxicity: reversible LV dysfunction (NOT dose-cumulative) - Often after anthracycline → synergistic - Reversible in 50-70%

Monitoring: echo every 3 months during treatment

Treatment: hold trastuzumab, start HF therapy, re-challenge after recovery often successful

293.1.0.1.2.3 VEGF Inhibitors (Bevacizumab, Aflibercept, Ramucirumab)

Toxicity: - HTN (10-30%) - Proteinuria - Arterial thromboembolism - Hemorrhage - LV dysfunction - Thrombotic microangiopathy

Management: BP control, monitor UA, watch for thromboembolism

293.1.0.1.2.4 Tyrosine Kinase Inhibitors (TKIs)

VEGF TKIs (sunitinib, sorafenib, axitinib, pazopanib): - HTN - LV dysfunction (~ 10%) - QT prolongation - Arrhythmia

BCR-ABL TKIs (imatinib, dasatinib, nilotinib, ponatinib, bosutinib): - Ponatinib: arterial thrombosis, MI, stroke (~ 30%) - Nilotinib: PAD, vascular events - Dasatinib: pulmonary HTN (rare, may reverse) - Imatinib: relatively safer

BTK Inhibitors (ibrutinib, acalabrutinib): - AF (10-15%) - Bleeding (esp on anticoagulation) - HTN - Ventricular arrhythmias

Management: cardio-oncology consultation, optimize CV risk factors, switch drug if severe

293.1.0.1.2.5 Proteasome Inhibitors (Carfilzomib, Bortezomib)
  • HF, HTN, arrhythmia
  • Carfilzomib > bortezomib for HF
  • Volume management, BP control
293.1.0.1.2.6 Immune Checkpoint Inhibitors (ICI)

Drugs: pembrolizumab, nivolumab, ipilimumab, atezolizumab, durvalumab, cemiplimab

Cardiotoxicity: - Myocarditis (rare 0.5-1.5%, but 50% mortality if severe) - Pericarditis, pericardial effusion - Arrhythmia - Conduction abnormalities (heart block) - Vasculitis (uncommon) - Takotsubo

Risk Factors: - Combination ICI (e.g., nivolumab + ipilimumab) - Pre-existing CV disease - DM - Multi-irAE patient

Clinical: - Onset typically 2-12 weeks after start - Symptoms: dyspnea, chest pain, palpitations, syncope, fatigue - Severe: cardiogenic shock, VT/VF, complete heart block

Diagnosis: - Troponin (sensitive) - ECG: arrhythmia, conduction - BNP/NT-proBNP - Echo: LV dysfunction - CMR: T2 hyperintensity + LGE (Lake Louise criteria) - EMB (endomyocardial biopsy): gold standard - NEW: 18F-FDG PET-CT for cardiac inflammation

Treatment: - Stop ICI - High-dose corticosteroids (methylprednisolone 1 g/d IV × 3 d, then 1 mg/kg/d taper) - Refractory: infliximab (anti-TNF), MMF, ATG, abatacept, JAK inhibitors (tofacitinib) - HF therapy + supportive - ECMO bridge in severe

293.1.0.1.2.7 5-FU + Capecitabine
  • Vasospasm → coronary vasospasm → chest pain, MI
  • Stop drug, treat with nitrates, CCB
  • May not be re-challenged
293.1.0.1.2.8 Cisplatin
  • Hypertension
  • Thromboembolism
  • Cardiovascular events long-term (especially in testicular cancer survivors)
293.1.0.1.2.9 Radiation Therapy

Chest radiation (especially mantle-field in Hodgkin’s, breast): - Premature CAD: years later - Pericardial disease: acute + chronic (constrictive) - Valvular disease: usually AR / AS late - Conduction abnormalities: AV block - Cardiomyopathy: restrictive - Carotid stenosis + premature atherosclerosis

Risk: dose > 30 Gy + young at exposure

Surveillance: lifelong CV follow-up; echo + stress testing periodically; consider statin

293.1.0.1.3 Diagnostic Workflow
293.1.0.1.3.1 Baseline (Pre-Treatment)
  • History (CV risk factors, family hx)
  • Physical exam
  • ECG, echo (LVEF, GLS — global longitudinal strain)
  • Troponin, BNP
  • Lipid panel, A1c, BP
  • CARDIOTOX risk score (2022 ESC) for risk stratification
293.1.0.1.3.2 During Treatment (Anthracycline / Trastuzumab)
  • Echo at intervals
  • Troponin + BNP if high risk
  • Watch for new symptoms
293.1.0.1.3.3 Post-Treatment
  • 6-12 months after completion
  • Then annual or biannual for high-risk
  • Lifelong for high-risk (anthracycline + radiation)
293.1.0.1.4 Cardiotoxicity Definition (2022 ESC)
293.1.0.1.4.1 CTR-CVT — LV Dysfunction
  • Symptomatic: HF symptoms + LVEF reduction
  • Asymptomatic:
    • LVEF reduction > 10% AND absolute LVEF < 50% (severe)
    • LVEF reduction > 10% AND absolute LVEF 50-54% (moderate)
    • Stable LVEF 50% + new GLS reduction > 15% (mild)
293.1.0.1.4.2 Other CTR-CVT Categories
  • HTN
  • Arterial vascular
  • Venous thrombosis
  • Arrhythmia
  • Pulmonary HTN
  • Myocarditis (especially ICI)
  • Pericardial
293.1.0.1.5 Cardioprotection
293.1.0.1.5.1 Anthracycline-Specific
  • Dexrazoxane (Zinecard / Cardioxane): iron chelator
    • Class IIa for high-risk + cumulative dose > 300 mg/m²
  • Liposomal doxorubicin (Doxil, Caelyx)
  • Limit cumulative dose (< 240-300 mg/m²)
  • Continuous infusion rather than bolus
293.1.0.1.5.2 Primary Prevention (Pre-Treatment)
  • Cardiac rehabilitation
  • BP control, statin if indicated
  • Stop smoking
  • Weight management
  • Exercise during treatment
293.1.0.1.5.3 Pharmacologic Prevention (Emerging)
  • PRADA trial 2024: candesartan + metoprolol for anthracycline
  • MANTICORE 101 Breast: bisoprolol or perindopril for trastuzumab
  • OVERCOME: enalapril + carvedilol for anthracycline
  • STOP-CA 2023: atorvastatin to prevent anthracycline cardiotoxicity (positive)
  • PROACT 2024: enalapril for anthracycline (similar)
  • SGLT2i in cardio-oncology: Empagliflozin in HFrEF inc post-anthracycline (emerging)
293.1.0.1.6 Treatment of Established Cardiotoxicity
293.1.0.1.6.1 LV Dysfunction
  • Standard HF therapy: ARNI / ACEi / ARB + β-blocker + MRA + SGLT2i
  • Carvedilol + ACEi most studied in this population
  • Cardiac rehabilitation
293.1.0.1.6.2 Hypertension
  • ACEi/ARB, CCB
  • Continue cancer therapy if BP controlled
  • Renal monitoring
293.1.0.1.6.3 Arrhythmias
  • AF: anticoagulation per CHA₂DS₂-VASc; DOACs OK
  • QT prolongation: monitor, hold drug, replenish electrolytes
293.1.0.1.6.4 Thrombosis
  • Cancer-associated VTE: DOAC (apixaban, edoxaban) per Caravaggio; LMWH for GI/GU cancers
  • ASA for arterial thrombosis (BCR-ABL TKI)
293.1.0.1.6.5 Myocarditis (ICI)
  • See above
293.1.0.1.7 Special Topics
293.1.0.1.7.1 Cardiac Rehabilitation in Cardio-Oncology
  • Beneficial for survivors
  • Exercise during treatment safe + effective (small RCTs)
  • Improves QOL, ↓ fatigue
293.1.0.1.7.2 Survivorship Care
  • Lifelong CV surveillance for high-risk
  • Childhood cancer survivors: structured follow-up
  • Patient-centered care plans
293.1.0.1.7.3 Pregnancy in Cancer Survivors
  • Anthracycline-exposed: 30% PPCM rate
  • Multi-disciplinary preconception counseling

293.1.0.2 🩺 床邊速查

  • Anthracycline: dose-dependent; > 300-350 mg/m² ↑ HF; dexrazoxane protects
  • Trastuzumab: reversible LV dysfunction; serial echo every 3 mo
  • ICI myocarditis: 0.5-1.5% but 50% mortality; stop ICI + IV methylpred 1 g/d; troponin elevation key
  • BCR-ABL TKI ponatinib: arterial thrombosis (~ 30%) → consider ASA, aggressive RF control
  • BTK inhibitor (ibrutinib): AF (10-15%), bleeding
  • 5-FU: vasospasm → MI; stop drug, nitrate/CCB
  • Radiation: late CAD, valve, pericarditis, conduction; lifelong follow-up