2022 ESC Guidelines on Cardio-Oncology

Authors, Journal, Affiliations, Type, DOI

• Chairpersons: Alexander R. Lyon (UK), Teresa López-Fernández (Spain)
• Journal: European Heart Journal 2022;43(41):4229–4361
• Affiliations: ESC Task Force on Cardio-Oncology; in collaboration with EHA, ESTRO, and IC-OS
• Type: Guideline (first ESC guideline on cardio-oncology)
• DOI: https://doi.org/10.1093/eurheartj/ehac244

Overview

This is the first ESC guideline on cardio-oncology, containing 272 new recommendations covering the entire continuum of cancer care from pre-treatment baseline risk assessment through active treatment surveillance to long-term cancer survivorship. It establishes harmonized definitions for cancer therapy-related cardiovascular toxicity (CTR-CVT), introduces the HFA-ICOS cardiovascular toxicity risk stratification framework (low/moderate/high/very high), and provides detailed monitoring protocols for 17 cancer treatment categories including anthracyclines, HER2-targeted agents, immune checkpoint inhibitors, and radiotherapy. Management of cardiovascular complications — including cancer therapy-related cardiac dysfunction (CTRCD), atrial fibrillation, venous thromboembolism, hypertension, and immune checkpoint inhibitor myocarditis — is addressed with treatment-specific and patient-specific algorithms. The overarching principle is integration of cardiology and oncology expertise through multidisciplinary team (MDT) approaches to maximize cancer treatment delivery while minimizing cardiovascular harm.

Keywords

Cardio-oncology · Cardiovascular toxicity · Anthracycline · Atrial fibrillation · Arrhythmias · Biomarkers · Cancer · Cancer survivors · Carcinoid syndrome · Amyloid light-chain cardiac amyloidosis · Cardiac magnetic resonance · Cardiac tumour · Cardiotoxicity · Coronary artery disease · Chemotherapy · Echocardiography · Heart failure · Haematopoietic stem cell transplantation · Hormone therapy · Hypertension · Immunotherapy · Myocarditis · Pulmonary hypertension · Thrombosis · Risk stratification · Trastuzumab · Valvular heart disease · VEGFi · Venous thromboembolism · QTc prolongation · Radiotherapy · Strain

Key Takeaways

Introduction and Scope

• First ESC cardio-oncology guideline with 272 new recommendations. CTR-CVT risk is a dynamic variable that changes throughout the cancer care continuum (before, during, and after treatment). The absolute risk depends on baseline risk and changes with exposure to cardiotoxic therapies over time.
• Cancer and CVD are the two leading causes of mortality in developed countries. Declining cancer mortality (since 1990s) → increasing cancer survivors → increasing CTR-CVT burden. Effective management requires dedicated cardio-oncology expertise.
• Cardio-oncology care pathways stratify follow-up by risk: Low risk = standard oncology surveillance; Moderate risk = cardiology referral at CV toxicity; High/very high risk = cardiology referral before treatment + cardioprotective strategies + intensive TTE surveillance.

Cancer Therapy-Related Cardiovascular Toxicity (CTR-CVT) Definitions

• CTRCD (cancer therapy-related cardiac dysfunction): Graded by severity:
  • Symptomatic CTRCD: Mild (HF symptoms, no dose intensification) → Moderate (outpatient diuretic intensification) → Severe (HF hospitalisation) → Very severe (inotropes/MCS/transplant consideration)
  • Asymptomatic CTRCD: Mild (LVEF ≥50% + new GLS decline >15% and/or new biomarker rise) → Moderate (new LVEF reduction by ≥10 pp to 40–49%; OR <10 pp reduction to 40–49% + GLS decline >15% OR new biomarker rise) → Severe (new LVEF reduction to <40%)
• ICI myocarditis (immune checkpoint inhibitor): Pathohistological (EMB: multifocal inflammatory cell infiltrates + cardiomyocyte loss) or clinical (cTn elevation + ≥1 major criterion [CMR diagnostic] or ≥2 minor criteria, after ACS exclusion)

Baseline CV Toxicity Risk Stratification (HFA-ICOS Tool)

• Risk stratification is Class I before all potentially cardiotoxic anticancer therapy.
• HFA-ICOS tool (Class IIa/C) categorises patients into Low / Moderate / High / Very High risk across six treatment categories: anthracyclines, HER2-targeted therapies, VEGFi, BCR-ABL inhibitors, multiple myeloma therapies, RAF/MEK inhibitors.
• Very high risk factors (any one → VH): pre-existing HF/cardiomyopathy/CTRCD (anthracyclines, HER2, MM); prior trastuzumab (for HER2 therapy); arterial thrombosis with TKI (BCR-ABL); prior VTE in MM; cardiac amyloidosis in MM.
• High risk factors (any one → H): LVEF <50% (all categories); age ≥80 (anthracyclines/HER2); severe VHD, MI/PCI/CABG, stable angina (anthracyclines/HER2); prior anthracycline exposure (multiple categories); mediastinal RT.
• Risk thresholds for anthracycline cumulative dose: ≥250 mg/m² doxorubicin equivalent is higher risk. Anthracycline equivalence dose ratios: epirubicin ×0.8; daunorubicin ×0.6; mitoxantrone ×10.5; idarubicin ×5.
• Actions by risk level: Low = oncology follow-up, no delay; Moderate = consider cardiology referral (IIb); High/VH = mandatory cardiology referral (I) + MDT risk/benefit discussion + cardioprotective strategies (IIa).

Baseline Assessment

• ECG: Class I for all patients starting cancer therapy.
• Echocardiography: Class I (3D preferred for LVEF; GLS in all patients) at baseline for high/VH risk. 3D echocardiography is recommended as preferred modality (Class I/B).
• Cardiac biomarkers (cTn + NP): Class I at baseline in all patients at risk of CTRCD if biomarkers will be tracked during treatment.
• Cardiac MRI: Consider if echo is non-diagnostic quality.

Prevention and Surveillance During Treatment (Section 5)

General Principles (Section 5.1)

• CTR-CVT risk varies by cancer type and stage, anticancer drugs, doses, and underlying comorbidities. Drug–drug or drug–radiation combinations may have synergistically toxic effects depending on timing (sequential vs. concomitant) and pre-existing comorbidities.
• CVD and cancer share common modifiable and non-modifiable risk factors. First step: optimise lifestyle — smoking cessation, restrict alcohol to ≤100 g/week, maintain adequate physical activity. Exercise during chemotherapy positively impacts cardiorespiratory fitness; poor CRF is associated with higher prevalence of acute and chronic CTR-CVT.
• Electrolyte correction: Hypokalaemia and hypomagnesaemia must be corrected throughout cancer therapy (synergistic arrhythmia and QTc risk with many anticancer drugs).
• Polypharmacy: Reduce non-essential drugs that interfere with cancer therapies; actively monitor CV side effects and drug–drug interactions. Intensive treatment of hypertension, DM, and dyslipidaemia required throughout.
• Shared care plan: CV risk management plan should be coordinated between the cancer specialist team, primary care physician, and patient.

Primary Prevention Strategies (Section 5.2)

• Primary prevention aims to avoid or minimise CV damage due to therapy in patients without pre-existing CVD. Requires MDT discussion (oncologist + cardiologist) for complex patients.

Anthracycline primary prevention (Section 5.2.1):

• Neurohormonal therapies (ACE-I/ARB, beta-blockers, MRA) during anthracycline chemotherapy reduce risk of significant LVEF decline in several small RCTs. Meta-analyses confirm benefit in preventing LVEF reduction, but no clear reduction in overt HF — likely because most trials enrolled low-baseline-risk patients. Larger RCTs in high-risk populations are needed.
• Dexrazoxane: Cardioprotective against anthracycline-induced CTRCD via iron chelation. Approved for adult patients receiving high cumulative anthracycline doses (EMA: ≥350 mg/m² doxorubicin equivalent; FDA: ≥300 mg/m²). Dosing: 10:1 ratio dexrazoxane:doxorubicin (e.g. 500 mg/m² per 50 mg/m² doxorubicin), infused ≥30 min before each anthracycline cycle. Class IIa/B for high/VH risk.
• Liposomal anthracyclines (pegylated and non-pegylated liposomal doxorubicin): Modified pharmacokinetics and tissue distribution without compromising antitumour efficacy. Less cardiotoxic than conventional doxorubicin (meta-analysis of 19 trials). Approved for metastatic BC, advanced ovarian cancer, AIDS-related Kaposi sarcoma, and MM. Class IIa/B for high/VH risk.
• ACE-I/ARB + beta-blockers (at HF doses; preferred beta-blocker: carvedilol, or bisoprolol/metoprolol succinate/nebivolol): Should be considered for primary prevention in high/VH risk patients receiving anthracyclines and/or anti-HER2 therapies: Class IIa/B. Also for high/VH risk patients receiving VEGFi, bevacizumab, RAF/MEK inhibitors, PI, dasatinib, ponatinib, or osimertinib: Class IIa/C.
• Statins: Should be considered for primary prevention in adult patients at high/VH CV toxicity risk (per HFA-ICOS): Class IIa/B.

RT primary prevention (Section 5.2.2):

• Modern heart-sparing RT techniques: intensity-modulated RT, respiratory gating/deep-inspiration breath-hold (BC, lymphoma, lung cancer), image-guided RT, proton beam therapy. Goal: minimise mean heart dose (MHD).
• No proven medical therapies to prevent RT-induced CV toxicity. Tight CVRF control is recommended as one component of RT-induced CVD is acceleration of pre-existing CAD.
• Where RT has only a consolidating role and RT-induced CV risk is very high → MDT risk/benefit discussion: Class I/C.

Primary prevention recommendation summary:

• CVRF management per 2021 ESC CVD Prevention Guidelines before, during, and after cancer therapy (without delaying cancer treatment): Class I/C
• Dexrazoxane in high/VH risk receiving anthracyclines: Class IIa/B
• Liposomal anthracyclines in high/VH risk receiving anthracyclines: Class IIa/B
• ACE-I/ARB + beta-blockers in high/VH risk (anthracyclines/anti-HER2): Class IIa/B
• ACE-I/ARB + beta-blockers in high/VH risk (VEGFi, RAF/MEK, PI, dasatinib, ponatinib, osimertinib): Class IIa/C
• Statins in adult patients at high/VH CV toxicity risk: Class IIa/B

Secondary Prevention Strategies (Section 5.3)

• Secondary prevention targets patients with pre-existing CVD (including prior CTR-CVT) and those developing new CTR-CVT during cancer therapy.
• CVD and comorbidities should receive optimal guideline-based therapy before and during cancer treatment — without delaying cancer therapy.
• Regular clinical assessments, physical examinations, 12-lead ECG, TTE, and cardiac biomarkers are recommended; frequency is guided by baseline risk and emergence of new CTR-CVT.
• Management of CVD per applicable ESC Guidelines: Class I/C.

Cardiovascular Surveillance During Cancer Therapies (Section 5.4)

Cardiac serum biomarkers (Section 5.4.1):

• cTn and NP are used for CTRCD screening, diagnosis, and guiding therapy during cancer treatment. The timing and pattern of biomarker release differ by cancer treatment type — rises must be interpreted in clinical context (treatment timing, comorbidities).
• No established cancer-specific cut-offs or reference values exist for NP or cTn. Values are affected by age, sex, renal function, obesity, infections, and comorbidities (AF, PE). Local laboratory reference ranges apply.

Cardiac imaging (Section 5.4.2):

• Cardiac imaging plays a central role in CTRCD detection. Frequency of monitoring is adapted to baseline risk and expected CTR-CVT manifestation.
• Same imaging modality (3D-TTE, 2D-TTE, or CMR) should be used throughout treatment to minimise inter-technique variability: Class I recommendation.
• 3D-TTE is the preferred modality: Assess 3D-LVEF + GLS at all monitoring time-points.
• GLS threshold for asymptomatic mild CTRCD: Relative GLS decrease >15% from baseline — this threshold maximises specificity and minimises overdiagnosis. Use the same vendor for serial GLS measurements to accurately compare values over time.
• CMR: Should be considered when TTE is unavailable or non-diagnostic (including fast strain-encoded CMR when available).
• MUGA: Third-line modality only.
• Perform cardiac imaging at any time if patients receiving cardiotoxic therapies develop new cardiac symptoms.

Drug-Specific Monitoring Protocols (Section 5.5)

Anthracycline Chemotherapy (Section 5.5.1)

• Anthracycline-induced CTRCD is dose-dependent and cumulative; onset is variable — may present during therapy or years later. Risk classification (Table 4 / HFA-ICOS) drives the frequency of TTE and biomarker monitoring.
• TTE monitoring:
  • Baseline TTE: Class I/B (all patients before anthracycline)
  • TTE within 12 months of completing treatment: Class I/B (all adults)
  • TTE every 2 cycles + within 3 months post-treatment: Class I/C (high/VH risk)
  • Additional TTE after cumulative dose ≥250 mg/m² doxorubicin equivalent: Class IIa/C (moderate risk); Class IIb/C (low risk)
• Cardiac biomarkers (cTn + NP):
  • Baseline NP + cTn: Class I/B (high/VH risk); Class IIa/C (low/moderate risk)
  • Serial cTn + NP before every cycle + at 3 and 12 months post-treatment: Class I/B (high/VH risk)
  • Serial cTn + NP every 2 cycles + within 3 months post-treatment: Class IIa/C (moderate risk or low risk receiving ≥250 mg/m²); Class IIb/C (low risk)

HER2-Targeted Therapies (Section 5.5.2)

• HER2-targeted therapies (trastuzumab, pertuzumab, trastuzumab emtansine, neratinib, tucatinib, trastuzumab deruxtecan) may cause LVD in up to 15–20% of patients. LV function surveillance is based on LVEF and GLS before and every 3 months during treatment.
• When anthracycline is required before anti-HER2 therapy, sequential use (anthracyclines → taxanes → anti-HER2) significantly reduces CTRCD incidence vs. concomitant use.
• TTE monitoring:
  • Baseline TTE: Class I/B (all patients)
  • Neoadjuvant/adjuvant setting: TTE every 3 months + within 12 months after completing treatment: Class I/B
  • Low-risk HER2+ early BC, asymptomatic with normal assessment at 3 months: may reduce monitoring to every 4 months: Class IIb/C
  • High/VH risk early BC: more frequent TTE during treatment: Class IIa/C
  • Metastatic HER2+ disease: TTE every 3 months in year 1; reduce to every 6 months if asymptomatic without CV toxicity: Class I/C
  • High/VH risk metastatic disease: more frequent TTE (every 2–3 cycles) may be considered: Class IIb/C
• Cardiac biomarkers:
  • Baseline NP + cTn: Class I/C (high/VH risk)
  • Serial NP + cTn every 2–3 cycles + at 3 and 12 months post-treatment: Class IIa/C (high/VH risk early BC)
  • Baseline cTn (post-anthracycline, pre-anti-HER2): Class IIa/A (low/moderate risk) — elevated cTn predicts higher risk of trastuzumab-induced CTRCD
  • Serial NP + cTn at baseline, every 3 months, 12 months post-treatment: Class IIb/C (low/moderate risk early BC)

Fluoropyrimidine Cardiotoxicity (Section 5.5.3)

• 5-FU and capecitabine (GI malignancies, advanced breast cancer): Most common CTR-CVTs are angina pectoris, ischaemia-related ECG changes, hypertension, Takotsubo syndrome, and MI (even with normal coronary arteries). Rarer: myocarditis, arrhythmias, peripheral arterial toxicity (Raynaud, ischaemic stroke).
• Incidence of myocardial ischaemia up to 10%; varies by dose, schedule, and route. Mechanism: coronary vasospasm + endothelial injury. Symptoms typically at rest, within days of drug administration.
• Risk markedly increased in patients with pre-existing CAD.
• Baseline assessment: CV risk assessment including BP, ECG, lipid profile, HbA1c, SCORE2/SCORE2-OP (Class I/C). Baseline TTE in patients with history of symptomatic CVD (Class I/C). Screening for CAD may be considered in high/VH risk (Class IIb/C).
• Rechallenge after vasospasm: Controversial; can be considered in monitored unit after exclusion of severe CAD (CT/coronary angiography) + initiation of prophylactic long-acting nitrates and CCBs.

Vascular Endothelial Growth Factor Inhibitors — VEGFi (Section 5.5.4)

• VEGFi (monoclonal antibodies: bevacizumab, ramucirumab, aflibercept; TKIs: sunitinib, sorafenib, axitinib, pazopanib, lenvatinib, cabozantinib, regorafenib, vandetanib) are used for renal, thyroid, and hepatocellular carcinomas among others. Associated with hypertension (class effect, 20–80%), LVD/HF, QTc prolongation, acute arterial events, and VTE. Goal is to continue VEGFi as long as possible with CV treatment optimisation.
• BP monitoring:
  • BP at every clinical visit: Class I/C
  • Daily home BP monitoring during first cycle, after each dose increase, and every 2–3 weeks thereafter: Class I/C. When VEGFi stops, anticipate BP drop and reduce antihypertensives accordingly.
• ECG / QTc monitoring:
  • In patients at moderate/high risk of QTc prolongation: QTc monitoring monthly during first 3 months and every 3–6 months thereafter: Class I/C. Consider ECG at 2 weeks in high-risk patients and after any dose increase.
• TTE monitoring:
  • Baseline TTE: Class I/C (high/VH risk); Class IIa/C (low/moderate risk)
  • TTE every 4 months during year 1: Class IIb/C (moderate risk)
  • TTE every 3 months during year 1: Class IIa/C (high/VH risk); additional TTE at 4 weeks in selected VH-risk patients
  • TTE every 6–12 months: Class IIa/C (moderate/high risk requiring long-term VEGFi)
• NP monitoring:
  • NP at baseline then every 4 months during year 1: Class IIb/C (moderate risk)
  • NP at baseline, 4 weeks after starting, then every 3 months during year 1: Class IIa/C (high/VH risk)

Multitargeted Kinase Inhibitors Targeting BCR-ABL (Section 5.5.5)

• BCR-ABL TKIs (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) treat CML. Toxicities are drug-specific: dasatinib → group 1 PAH, HF, pleural/pericardial effusion; nilotinib and ponatinib → vascular events (PAD, ATE, MI); second-generation TKIs may prolong QTc. CV toxicity risk is higher with age >65 years, DM, hypertension, and pre-existing CAD.
• CV risk assessment:
  • Baseline CV risk assessment (BP, ECG, lipid profile, HbA1c): Class I/C (all second-/third-generation BCR-ABL TKI)
  • CV risk assessment every 3 months in year 1, then every 6–12 months during nilotinib or ponatinib: Class I/C
• QTc monitoring:
  • QTc at baseline, 2 and 4 weeks after starting nilotinib, and 2 weeks after any dose increase: Class IIa/C
• TTE monitoring:
  • Baseline TTE: Class I/C (dasatinib — mandatory); Class IIa/C (all other second-/third-generation BCR-ABL TKI)
  • TTE every 3 months during year 1: Class IIa/C (high/VH risk on dasatinib or ponatinib)
  • TTE every 6–12 months: Class IIb/C (long-term ponatinib or dasatinib)
• PAD surveillance:
  • Serial ankle-brachial index may be considered to detect subclinical peripheral vascular disease: Class IIb/C (especially nilotinib, ponatinib)

Bruton Tyrosine Kinase (BTK) Inhibitors (Section 5.5.6)

• Used for lymphoid malignancies (CLL, mantle cell lymphoma, Waldenström, marginal zone lymphomas). Typically elderly patients with frequent CV comorbidities.
• Ibrutinib (first-generation): Associated with bleeding diathesis, infections, hypertension, AF (major toxicity), HF, and ventricular arrhythmias (without QT prolongation).
• Acalabrutinib (second-generation, greater BTK selectivity): Non-inferior PFS vs. ibrutinib with lower incidence of symptomatic CV events. However, grade ≥3 AF and AF in patients ≥75 years or with prior AF history were comparable between groups. CV event risk comparable in patients with pre-existing CVRFs/CVD. Currently insufficient data for different monitoring strategies.
• Monitoring:
  • BP at every clinical visit (Class I/B). Weekly home BP monitoring during first 3 months, monthly thereafter (Class IIa/C).
  • Baseline TTE in high-risk patients (male, age ≥65, HTN, DM, QTc ≥480 ms, AF, HF, cardiomyopathy, severe VHD) (Class I/C).
  • Opportunistic AF screening (pulse-taking or ECG rhythm strip) at every clinical visit (Class I/C). TTE in all patients who develop AF (Class I/C).
• Bleeding risk: Ibrutinib should be temporarily interrupted for DAPT requirements and 3–7 days before invasive procedures. Platelet transfusion for emergency interventions.

Multiple Myeloma Therapies (Section 5.5.7)

• Multiple myeloma drugs include proteasome inhibitors (PI: bortezomib, carfilzomib, ixazomib), IMiDs (thalidomide, lenalidomide, pomalidomide), dexamethasone, and monoclonal antibodies (daratumumab). PI are associated with hypertension, HF (especially HFpEF), ACS, arrhythmias, PH, and VTE. Carfilzomib carries the highest HF risk (7–23% incidence). MM patients are at elevated thrombotic risk, especially with PI + IMiD combination.
• BP monitoring:
  • BP at every clinical visit: Class I/C (PI)
  • Weekly home BP monitoring in first 3 months, monthly thereafter: Class IIa/C (PI)
• Cardiac biomarkers:
  • Baseline NP: Class I/C (high/VH risk PI); Class IIa/C (low/moderate risk PI)
  • NP at baseline and every cycle during first 6 cycles: Class IIa/B (carfilzomib or bortezomib); every 2 months for ixazomib
  • NP + cTn at baseline and every 3–6 months: Class I/B (AL cardiac amyloidosis patients on PI)
• TTE monitoring:
  • Baseline TTE (including assessment for AL cardiac amyloidosis): Class I/C (all MM patients before PI)
  • TTE every 3 cycles: Class IIa/B (high/VH risk carfilzomib); Class IIb/C (low/moderate risk carfilzomib)
  • TTE every 3–6 months: Class IIa/C (AL cardiac amyloidosis on PI)
• VTE prophylaxis (PI + IMiD):
  • Therapeutic LMWH: Class I/B (previous VTE)
  • Prophylactic LMWH during first 6 months: Class I/A (VTE risk factors, excluding prior VTE)
  • Aspirin as alternative to LMWH if no/one VTE risk factor (excluding prior VTE): Class IIa/B
  • Low-dose apixaban (2.5 mg BID) or rivaroxaban (10 mg OD) as alternative: Class IIb/C

RAF/MEK Inhibitor Treatment (Section 5.5.8)

• RAF inhibitors (vemurafenib, dabrafenib, encorafenib) and MEK inhibitors (trametinib, cobimetinib, binimetinib, selumetinib) are used for metastatic melanoma with BRAF V600 mutation, predominantly in combination. Main CV toxicities: hypertension, PE/VTE, CTRCD (all RAF/MEK combinations), and QTc prolongation (cobimetinib/vemurafenib combination only). MEK inhibitors drive most cardiac complications; RAF inhibitors enhance MEK toxicity — hypertension and LVD are ~2× more frequent with combination vs. RAF monotherapy. CTRCD can occur from 1 month to 2 years after starting therapy.
• BP monitoring: BP at each clinical visit + weekly outpatient monitoring during first 3 months + monthly thereafter: Class I/C
• ECG monitoring: For cobimetinib/vemurafenib: ECG at 2 and 4 weeks after initiation, then every 3 months thereafter: Class I/C
• TTE monitoring:
  • Baseline TTE: Class I/C (high/VH risk); Class IIb/C (low/moderate risk)
  • TTE every 4 months during year 1: Class IIa/C (high/VH risk)

Immune Checkpoint Inhibitors — Monitoring (Section 5.5.9)

• ICI (anti-CTLA-4: ipilimumab, tremelimumab; anti-PD-1: nivolumab, pembrolizumab, cemiplimab; anti-PD-L1: atezolizumab, avelumab, durvalumab) cause immune-related CV events including myocarditis, pericarditis, arrhythmias, MI, and non-inflammatory HF. High-risk features: dual ICI therapy, combination with other cardiotoxic therapies, prior ICI-related non-CV events, prior CTRCD or CVD.
• Baseline (all patients): ECG + cTn + NP: Class I/B
• Baseline (high-risk patients): TTE: Class I/B; consider TTE in all patients: Class IIb/C
• During treatment:
  • Serial ECG + cTn before cycles 2, 3, and 4; if normal, reduce to every 3 cycles until completion: Class IIa/B
  • Any new cTn elevation, ECG abnormality, or cardiac symptoms → prompt cardio-oncology evaluation + TTE + CMR if myocarditis suspected
• Long-term (>12 months ICI):
  • CV assessment (examination, BP, NP, lipids, HbA1c, ECG) every 6–12 months: Class I/C (high-risk); Class IIb/C (all patients)
• JAVELIN trial note: Routine TTE monitoring in asymptomatic low-risk ICI patients showed no additional clinical value.

Androgen Deprivation Therapy (ADT) CV Toxicity (Section 5.5.10)

• Prescribed in ~40% of men with prostate cancer. GnRH agonists (goserelin, leuprorelin, triptorelin) are most common — associated with increased CV risk and mortality, particularly in patients >60 years.
• Main CV effects: Hypertension, diabetes, ischaemic heart disease, CTRCD. Uncommon QTc prolongation; rare TdP (testosterone blockade affects ventricular repolarization).
• GnRH antagonists (degarelix, relugolix): Preclinical and clinical data (HERO trial) suggest lower overall mortality and CV events vs. agonists. PRONOUNCE trial showed no difference in MACE at 1 year (stopped early; optimal CVRF management in both arms).
• GnRH antagonist should be considered in patients with pre-existing symptomatic CAD requiring ADT (Class IIa/B).
• Monitoring:
  • Baseline CV risk assessment + SCORE2/SCORE2-OP in patients without pre-existing CVD (Class I/B).
  • Baseline and serial ECGs in patients at risk of QTc prolongation (Class I/B).
  • Annual CV risk assessment (BP, lipids, fasting glucose, HbA1c, ECG) during ADT (Class I/B).
• 2nd-generation antiandrogens (apalutamide, darolutamide, enzalutamide) and abiraterone (androgen metabolism inhibitor): Hypertension very common; HF, IHD/MI, and QTc prolongation reported at varying frequencies.

Endocrine Therapies for Breast Cancer (Section 5.5.11)

• Selective oestrogen receptor modulators (tamoxifen, toremifene) and aromatase inhibitors (AI: letrozole, anastrozole, exemestane) are used in hormone receptor-positive BC. AI increase the risk of dyslipidaemia, metabolic syndrome, hypertension, HF, and MI; longer AI duration is associated with increased CVD risk. Tamoxifen increases VTE risk significantly and is not recommended in patients with thrombotic risk. Toremifene and high-dose tamoxifen prolong QTc (no data at standard BC dose of 20 mg/day).
• Monitoring:
  • Baseline CV risk assessment (BP, lipids, fasting glucose, HbA1c, ECG) + SCORE2/SCORE2-OP: Class I/C (patients without pre-existing CVD)
  • Annual CV risk assessment: Class I/C (high SCORE2/SCORE2-OP risk)
  • CV risk assessment every 5 years: Class IIa/C (low/moderate SCORE2/SCORE2-OP risk)
  • Cholesterol and BP monitoring regularly during AI therapy
  • Smoking cessation strongly recommended (reduces CAD risk during AI and VTE during tamoxifen)

Cyclin-Dependent Kinase 4/6 Inhibitors (Section 5.5.12)

• CDK 4/6 inhibitors (palbociclib, ribociclib, abemaciclib) in combination with endocrine therapy are approved for hormone receptor-positive/HER2-negative metastatic BC. Ribociclib carries the greatest QTc prolongation risk (Phase III trials incorporated routine ECG monitoring). Avoid ribociclib with QT-prolonging drugs, strong CYP3A inhibitors, and tamoxifen (synergistic QTc risk).
• QTc monitoring:
  • QTc at baseline, day 14 of first cycle, before second cycle, with any dose increase: Class I/A (ribociclib)
  • QTc at baseline, day 14, and day 28: Class I/A (ribociclib)
  • QTc monitoring should be considered: Class IIa/C (palbociclib or abemaciclib if baseline QTc above normal or other QTc-prolonging conditions)
• EMA QTc thresholds for ribociclib: Interrupt if QTcF >480 ms; resume at same dose if resolves to <481 ms; reduce dose if ≥481 ms recurs.

ALK Inhibitors and EGFR Inhibitors (Sections 5.5.13–5.5.14)

• ALK inhibitors (crizotinib, alectinib, brigatinib, ceritinib, lorlatinib) cause sinus bradycardia, AV block, QTc prolongation, hypertension, hyperglycaemia, and dyslipidaemia. ACS and HF are rare (crizotinib). Lorlatinib commonly causes dyslipidaemia.
  • Baseline ECG + CV risk assessment: Class I/C
  • ECG at 4 weeks and every 3–6 months during ALK inhibitor therapy: Class IIa/C
  • Home BP monitoring during brigatinib, crizotinib, or lorlatinib: Class IIa/C
  • Cholesterol every 3–6 months during crizotinib and lorlatinib: Class IIa/C
• Osimertinib (EGFR-TKI): Increased risk of QTc prolongation, AF, VTE, LVD, and HF. One study showed 11% LVEF decline <53% with TTE surveillance. Pre-existing hypertension and older age are risk factors for LVD/HF. Monitor magnesium closely (osimertinib causes hypomagnesaemia → QTc risk).
  • Baseline CV risk assessment + ECG + TTE before starting osimertinib: Class I/B
  • TTE every 3 months during osimertinib therapy: Class IIa/B

CAR-T and TIL Therapies — Monitoring (Section 5.5.15)

• Baseline CV evaluation (ECG + NP + cTn): Class I/C (all patients before CAR-T and TIL)
• Baseline TTE: Class I/C (patients with pre-existing CVD); Class IIa/C (all patients)
• CRS screening: If CRS grade ≥2 (ASTCT criteria) develops → NP + cTn + TTE: Class I/C
• Early cardiac evaluation for any cTn rise: NP + ECG + TTE; CMR if myocarditis suspected (see Section 6.1.4 for management)
• TIL therapy: same baseline assessment pathway as CAR-T

Radiotherapy (Section 5.5.16)

• RT increases risk of CVD and PAD; no radiation dose is completely 'safe' for the heart. Risk categorisation is based on mean heart dose (MHD) rather than prescribed dose:
  • Very high risk: MHD >25 Gy or MHD >15 Gy + cumulative doxorubicin ≥100 mg/m²
  • High risk: MHD 5–25 Gy + cumulative doxorubicin ≥100 mg/m² or MHD >15–25 Gy alone
  • Moderate risk: MHD 5–15 Gy alone
  • Low risk: MHD <5 Gy alone
• Heart-sparing strategies: intensity-modulated photon RT, deep inspiration breath-hold (BC, lymphoma, lung), respiratory-gated techniques, proton beam therapy.
• No RT-specific drug treatments to reduce CV events exist; optimisation of conventional CVRF is recommended before and after RT.
• Monitoring:
  • Baseline CV risk assessment (BP, lipids, fasting glucose, HbA1c, ECG) + SCORE2/SCORE2-OP: Class I/B (before RT to a volume including the heart)
  • Baseline TTE: Class IIa/C (patients with previous CVD before cardiac RT)

Haematopoietic Stem Cell Transplantation — HSCT (Section 5.5.17)

• HSCT survivors are at high long-term CV risk. Key risk factors: allogeneic HSCT (higher risk than autologous), multiple uncontrolled CVRF, pre-existing CVD (AF, sick sinus syndrome, VAs, CAD, MI, VHD, HF/LVEF <50%), prior anthracyclines (>250 mg/m² doxorubicin equivalent) or mediastinal RT, total body irradiation/cyclophosphamide conditioning, and GVHD.
• Early CV events (<100 days): AF most common; also HF, hypertension, hypotension, pericardial effusion, VTE.
• Late toxicities (>100 days): DM, dyslipidaemia, metabolic syndrome, hypertension, HF, CAD, conduction disorders, pericardial effusion. Acute GVHD → thrombosis + inflammatory myocardial damage; chronic GVHD → hypertension, DM, dyslipidaemia.
• Monitoring:
  • Baseline + serial CV risk assessment (3 and 12 months, then yearly): BP, ECG, lipids, HbA1c: Class I/C
  • Baseline TTE: Class I/C (all HSCT patients)
  • Baseline NP: Class IIa/C (before HSCT)
  • TTE at 3 and 12 months post-HSCT: recommended in high-risk HSCT recipients (LVEF and GLS can decrease after transplant)

Other Cancer Treatments (Section 5.5.18)

• Cyclophosphamide (high dose >140 mg/kg before HSCT): HF typically within days of administration. Cisplatin and oxaliplatin: vascular disease risk (vasospasm, MI, arterial and venous thrombosis) during and long-term; testicular cancer survivors at elevated vascular risk. Cisplatin rarely causes HF but high IV volume load can precipitate HF in pre-existing CVD.
• Arsenic trioxide (leukaemia, myeloma): QTc prolongation in 26–93% of patients; life-threatening VT reported. ECG weekly for first 8 weeks; electrolytes (K⁺, Mg²⁺, renal function) monitored — hypokalaemia and hypomagnesaemia common.
• FLT3 inhibitors (midostaurin, gilteritinib): QTc prolongation → close electrolyte surveillance and minimise drug–drug interactions. Gilteritinib-induced differentiation syndrome (fever, dyspnoea, pleuropericardial effusion, pulmonary oedema, hypotension) → early corticosteroids + haemodynamic monitoring.

Cancer Therapy-Related Cardiac Dysfunction — Management (Section 6.1)

Anthracycline CTRCD (Section 6.1.1)

• Severity-stratified oncology decisions:
  • Severe symptomatic CTRCD: Discontinue anthracycline (Class I/C). Rare exceptions via MDT with prevention strategies + close monitoring per cycle.
  • Moderate symptomatic CTRCD: Interrupt anthracycline (Class I/C). MDT decision to restart after LV function recovery.
  • Mild symptomatic CTRCD: MDT approach regarding interruption vs. continuation (Class I/C).
  • Severe asymptomatic CTRCD (LVEF <40%): Interrupt anthracycline + initiate HF therapy (Class I/C). MDT for restart decision.
  • Moderate asymptomatic CTRCD (LVEF 40–49%): Interrupt anthracycline + initiate HF therapy (Class I/C). MDT for restart decision.
  • Mild asymptomatic CTRCD (LVEF ≥50% + GLS decline >15% and/or biomarker rise): Continue anthracycline with CV monitoring (Class I/C).
• HF pharmacotherapy by severity:
  • Symptomatic or moderate/severe asymptomatic CTRCD: Full guideline-based HF therapy — ACE-I/ARB or ARNI + beta-blocker + SGLT2i + MRA; up-titrate to target doses per 2021 ESC HF guidelines (Class I/B).
  • Mild asymptomatic with GLS decline >15%: ACE-I/ARB and/or beta-blocker should be considered (Class IIa/B).
  • Mild asymptomatic with troponin elevation >ULN: ACE-I/ARB and/or beta-blocker should be considered (Class IIa/B).
  • Mild asymptomatic with NP elevation >ULN only: ACE-I/ARB and/or beta-blocker may be considered (Class IIb/C).
• Rechallenge strategies (when anthracycline must continue after CTRCD):
  • Minimize anthracycline dose administered.
  • Switch to liposomal anthracycline preparations (Class IIb/C).
  • Pre-treatment with dexrazoxane before each further cycle (Class IIb/C). EMA threshold: ≥350 mg/m² doxorubicin equivalent; FDA: ≥300 mg/m².
  • Continue ACE-I/ARB and beta-blockers at HF target doses.
  • Close cardiac monitoring every 1–2 cycles recommended when anthracycline restarted after CTRCD.
• Aerobic exercise: Beneficial effects before and during anthracycline chemotherapy demonstrated; recommended for patients who develop CTRCD (Class I).

HER2-Targeted Therapy CTRCD (Section 6.1.2)

• Key difference from anthracycline — more permissive continuation strategy:
  • Moderate-to-severe symptomatic CTRCD: Interrupt HER2 therapy + start HF therapy (Class I/B). MDT restart decision after LV recovery.
  • Mild symptomatic CTRCD: MDT approach regarding continue vs. interrupt; start HF therapy (Class I/C).
  • Severe asymptomatic CTRCD (LVEF <40%): Interrupt HER2 therapy + start HF therapy (Class I/C).
  • Moderate asymptomatic CTRCD (LVEF 40–49%): Continue HER2 therapy + start ACE-I/ARB and beta-blockers + frequent monitoring (Class IIa/B). This is a major departure from prior guidance that mandated interruption.
  • Mild asymptomatic CTRCD (LVEF ≥50% + GLS decline or biomarker rise): Continue HER2 therapy + consider ACE-I/ARB and/or beta-blockers (Class IIa/B).
• Restart protocol after interruption: Resume HER2 therapy when LVEF recovers ≥40% and patient is asymptomatic (Class IIa). Echo + cardiac biomarkers every 2 cycles for first 4 cycles after restart, then reduce frequency if stable.
• Refractory cases: In advanced cancer that only responds to trastuzumab, continuing therapy with LVEF <40% may be considered if no alternative exists (MDT decision).

ICI Myocarditis — Management (Section 6.1.3)

• Incidence: Rare (0.1–1.1%) but high fatality (~25–50%). Most frequently in first 12 weeks; late cases (>20 weeks) occur.
• Other ICI-related CV toxicities: Dyslipidaemia (OR 3.68), ACS, vasculitis, AV block, SVT/VT, sudden death, TTS, non-inflammatory LVD, pericarditis, pericardial effusion, ischaemic stroke.
• Diagnosis: New troponin elevation + CV symptoms or non-CV immune-related adverse events + new ECG abnormalities (AV/intraventricular conduction disorders, bradycardia, tachyarrhythmias). CMR (modified Lake Louise criteria) + TTE in all suspected cases. FDG-PET if CMR unavailable (low sensitivity; requires 18-h carbohydrate-free fast). EMB should be considered when non-invasive diagnosis is uncertain (Class IIa/C).
• Classification: Fulminant (haemodynamic instability, HF requiring ventilation, complete/high-grade AV block, significant VA) vs. Non-fulminant (symptomatic but stable, or incidental diagnosis).
• Management algorithm:
  • Interrupt ICI in all suspected cases (Class I/C).
  • Permanent cessation of ICI in confirmed myocarditis (Class I/C).
  • Methylprednisolone 500–1000 mg IV bolus daily × 3–5 days — start as soon as diagnosis is considered likely (Class I/C). In haemodynamically unstable patients, start while awaiting confirmatory testing.
  • If clinical improvement (cTn reduced >50% from peak within 24–72 h; LVD, AV block, arrhythmias resolved) → switch to oral prednisolone 1 mg/kg/day (max 80 mg), then wean by 10 mg/week under cTn + ECG surveillance (Class IIa/C). At 20 mg/day, reassess LV function + cTn; then 5 mg/week to 5 mg/day, then 1 mg/week steps.
  • Steroid-refractory (troponin not falling >50%, or AV block/VA/LVD persist after 3 days IV methylprednisolone): second-line immunosuppression should be considered (Class IIa/C). Options under investigation: IV mycophenolate mofetil, anti-thymocyte globulin, IV immunoglobulin, plasma exchange, tocilizumab, abatacept (CTLA-4 agonist), alemtuzumab, tofacitinib. Caution against infliximab for steroid-refractory myocarditis and HF.
  • Fulminant myocarditis: ICU admission (level 3) + IV methylprednisolone + optimal CV treatment including MCS when indicated (Class I/C).
  • A single dose of IV methylprednisolone should be considered in clinically unstable patients where ICI myocarditis is suspected but not yet confirmed (Class IIa/C).
• ICI rechallenge: MDT discussion after recovery. Depends on severity (fulminant vs. non-fulminant), alternative oncology options, adjuvant vs. metastatic indication, and reducing from dual to single ICI.
• Non-inflammatory HF with ICI: TTS, non-inflammatory LVD, post-MI HF. Late events. Treat per ESC HF guidelines; no immunosuppression if myocarditis excluded. ICI may continue after MDT review depending on HF severity.

CAR-T Cardiac Complications (Section 6.1.4)

• CV complications represent ~20% of adverse events with CAR-T therapy, associated with high mortality. Secondary to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome.
• Most common CV complications: Arrhythmias (77.6%) including QTc prolongation, VA, and AF; HF (14.3%); MI and VTE (0.5%).
• Workup: Resting 12-lead ECG, continuous ECG monitoring, TTE, cTn + NP.
• Severe cases: ICU admission (level 3) due to risk of malignant arrhythmias, circulatory collapse, multiorgan failure.
• CRS markers: Dramatic IL-6 elevation supports CRS diagnosis; CRP is non-specific and may lag by ≥12 hours.
• Management: Treat specific CV complication per ESC guidelines + CRS management (tocilizumab [anti-IL-6R antibody] + dexamethasone).
• TIL (tumour-infiltrating lymphocyte) therapies: Most frequent CV events are hypotension (requiring IV fluids/pressors), AF, and cTn elevation. Survival does not appear significantly affected.

Heart Failure During Haematopoietic Stem Cell Transplantation (Section 6.1.5)

• CV complications during HSCT — including congestive HF, arterial events, cardiac tamponade, and rhythm disturbances (AF, atrial flutter, SVT) — are uncommon but clinically relevant. Manage per specific ESC guidelines: HF, tachyarrhythmias, pericardial effusion, and ACS guidelines as applicable.
• Evidence on treatments during HSCT to prevent both acute and late CV toxicity is limited. ACE-I and beta-blockers may be effective for cardioprotection, but this requires further confirmation.
• Outpatient and home-based exercise and education programmes instituted after HSCT improve exercise capacity and quality of life. The role of exercise pre-habilitation prior to HSCT is currently under investigation.

Takotsubo Syndrome in Cancer (Section 6.1.6)

• High prevalence of malignancy in TTS patients; malignancy is a risk factor for worse TTS outcomes.
• Triggers: Malignancy itself, cancer treatments (5-FU, ICI, VEGFi), and stress of diagnosis/treatment.
• Workup: Clinical examination + ECG + TTE + cardiac biomarkers (cTn + NP) + CMR. Most require invasive coronary angiography to exclude MI. CCTA recommended if invasive angiography contraindicated (advanced malignancy, severe thrombocytopaenia). Imaging should be early (LVD can be transient).
• Management: Interrupt culprit cancer drug (Class I). Avoid QT-prolonging drugs during acute phase (Class III). CMR recommended to exclude myocarditis and MI (Class I/B). Coronary angiography/CCTA to exclude ACS (Class I/C).
• ICI-associated TTS: If myocardial inflammation present on CMR in TTS pattern → IV methylprednisolone (given overlap with ICI myocarditis). Role of immunosuppression otherwise unknown.
• After recovery: MDT discussion. If restarting culprit drug required from oncology perspective → regular cTn + NP monitoring before every cycle, TTE if new biomarker rise.

Coronary Artery Disease in Cancer (Section 6.2)

Acute Coronary Syndromes

• Cancer patients are at increased risk of CAD due to shared CVRFs, CV toxicity of cancer therapy, and a cancer-induced pro-inflammatory/prothrombotic state.
• ~3% of ACS patients have a cancer diagnosis; proportion is rising. Within 1 year of cancer diagnosis, risk of MACE, bleeding, and mortality is highest.
• Cancer treatments predisposing to ACS:
  • Accelerated atherosclerosis and plaque rupture: ADT (GnRH agonists), ICI, nilotinib, ponatinib, radiation therapy, VEGFi.
  • Vasospasm: Bleomycin, fluoropyrimidines, taxanes, VEGFi, vinca alkaloids.
  • Coronary thrombosis: Alkylating agents (cisplatin, cyclophosphamide), erlotinib, ICI, IMiDs, monoclonal antibodies (VEGFi, anti-CD20), nilotinib, platinum chemo, proteasome inhibitors, ponatinib, VEGFi.
• Invasive strategy recommended for STEMI or high-risk NSTE-ACS with life expectancy ≥6 months (Class I/B). PCI associated with lower adjusted MACE and all-cause mortality.
• Conservative non-invasive strategy should be considered in poor cancer prognosis (<6 months) and/or very high bleeding risk (Class IIa/C). PCI has not demonstrated mortality benefit in advanced cancer + NSTE-ACS vs. medical therapy.
• Stenting: Third-generation drug-eluting stents preferred (lower in-stent thrombosis). Balloon angioplasty only for severe thrombocytopaenia or urgent surgery.
• Antithrombotic strategy: DAPT with aspirin + clopidogrel (preferred over prasugrel/ticagrelor due to bleeding risk). Duration kept as short as possible (1–3 months) (Class IIa/C).
  • Ticagrelor/prasugrel may be considered only in low bleeding risk + excessive thrombotic risk (Class IIb/C).
  • Triple therapy (NOAC + single antiplatelet) for max 1 week if concurrent OAC indication.
• Thrombocytopaenia thresholds: Aspirin not recommended if platelets <10,000/µL (Class III). Clopidogrel not recommended if <30,000/µL; prasugrel/ticagrelor not recommended if <50,000/µL (Class III). PCI: minimum 30,000/µL; CABG: minimum 50,000/µL.
• CABG may be considered with extensive CAD not amenable to PCI, after MDT, when cancer prognosis >12 months.
• MINOCA: CMR to detect other causes (myocarditis, TTS).
• Post-ACS: Review cancer medications; stop drugs associated with thrombosis/MI. Restart only after MDT + alternative options explored.

Chronic Coronary Syndromes

• 5-FU/capecitabine can cause effort angina. Platinum-based chemo induces ischaemia in 1st–3rd cycles (usually in patients with underlying CAD). VEGFi-TKI: 2–3% cardiac ischaemia; VEGFi monoclonal antibody: 0.6–1.5%. Nilotinib, ponatinib, ICI accelerate atherosclerosis.
• Management per 2019 ESC CCS guidelines. Aggressive CVRF modification. Revascularization via MDT including cardio-oncology.
• Individualized DAPT duration recommended post-revascularization based on thrombotic/bleeding risk, cancer type/stage, and current treatment (Class I/C).

Valvular Heart Disease in Cancer (Section 6.3)

• New or worsening VHD may relate to CTRCD, ACS, pulmonary hypertension, endocarditis, cardiac tumours, or mechanical prosthetic valve thrombosis.
• Pre-existing severe VHD is a risk factor for CTRCD. In patients with mechanical valves, thrombosis vs. bleeding risk must be carefully balanced during chemotherapy.
• Severe VHD at baseline: MDT required before cancer therapy. Cardiac surgery is challenging in cancer (comorbidities, frailty, mediastinal fibrosis from prior RT, impaired wound healing).
• TAVI may be a viable option for cancer patients with severe aortic stenosis — limits recovery time and delay to cancer treatment (Class I/C).
• New VHD during cancer therapy: Screen for endocarditis; manage per 2021 ESC/EACTS VHD guidelines, considering cancer prognosis and patient preferences (Class I/C).
• If valve surgery or percutaneous treatment indicated → MDT on type of valve treatment and periprocedural cancer treatment management.

Cardiac Arrhythmias (Section 6.4)

Atrial Fibrillation in Cancer (Section 6.4.1)

• AF occurs in 2–16% of patients during cancer therapy; highest incidence post-lung surgery (6–32%). All cancer types increase AF risk vs. controls; risk depends on cancer type, stage, and treatment.
• Cancer-associated AF is associated with 2× higher stroke/thromboembolism risk and 6× higher HF risk compared with AF alone.
• Pathophysiology: Cancer × ageing × anticancer treatments × cancer surgery × inflammation × hypoxia × ANS imbalance × paraneoplastic mechanisms.
• Anticoagulation: Follow ABC pathway (2020 ESC AF guidelines). CHA2DS2-VASc score should be used for risk stratification but likely underestimates thromboembolic risk in cancer (Class IIa/C). Score = 0 in cancer may still carry meaningful stroke risk.
  • OAC recommended for CHA2DS2-VASc ≥2 (men) or ≥3 (women): Class I/C
  • OAC should be considered for score = 1 (men) or = 2 (women): Class IIa/C
  • Score = 0 (men) or 1 (women): may consider OAC after bleeding risk assessment: Class IIb/C
• TBIP anticoagulation algorithm for cancer + AF: T (thrombotic risk: CHA2DS2-VASc + cancer-related factors) → B (bleeding risk: thrombocytopaenia, GI/GU cancer, renal dysfunction, HAS-BLED score) → I (drug–drug Interactions: P-glycoprotein/CYP3A4 interactions with anticancer agents) → P (Patient preferences/drug access).
• NOAC preferred over LMWH and VKA (Class IIa/B) except for mechanical valves or moderate/severe mitral stenosis. Secondary analyses of ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48 support NOAC safety in cancer.
• LMWH should be considered when NOACs are not suitable (active cancer + unsuitable for NOAC): Class IIa/C.
• Beta-blockers preferred for rate control (avoid diltiazem/verapamil due to drug interactions and negative inotropy): Class IIa/C.
• LAA occlusion may be considered in cancer + AF with contraindication to long-term OAC and life expectancy >1 year: Class IIb/C.
• Post-operative AF in cancer surgery: 4–5× risk of AF recurrence over 5 years — anticoagulation should be considered in patients at stroke risk.
• Antiplatelet therapy is NOT recommended for stroke prevention in AF + cancer: Class III.

Ventricular Arrhythmias and QTc Prolongation (Section 6.4.2)

• Many anticancer drugs prolong QTc → torsade de pointes risk. Monitor QTc before and during treatment with QTc-prolonging agents.
• QTc classification during cancer therapy: Grade 1 (<480 ms / <500 ms if baseline QTc 450–480 ms); Grade 2 (480–499 ms); Grade 3 (≥500 ms); Grade 4 (≥500 ms + TdP/VF/cardiac arrest).
• Correct modifiable risk factors: electrolytes, drugs, infection.

Arterial Hypertension (Section 6.5)

• VEGFi (bevacizumab, sunitinib, sorafenib) are particularly associated with hypertension (20–80%). Target BP <130/80 mmHg in cancer patients receiving VEGFi (Class IIa).
• First-line agents: ACE-I/ARB preferred for VEGFi-associated hypertension; calcium channel blockers acceptable but amlodipine preferred over verapamil/diltiazem.

Venous Thromboembolism in Cancer (Section 6.6)

• Cancer is a major independent risk factor for VTE (4–7× higher risk than general population). Anticoagulation is first-line treatment.
• LMWH or NOAC (rivaroxaban, apixaban, edoxaban) recommended for VTE treatment in cancer (Class I); NOACs may carry higher bleeding risk in GI/GU malignancies — prefer LMWH in those settings.
• TBIP framework applies to VTE anticoagulation decisions as well as AF.

Bleeding Complications in Cancer (Section 6.7)

• More common in cancer vs. non-cancer patients. Directly tumour-related or indirectly from chemo/RT-induced mucosal barrier weakening.
• High-risk patients: GI and GU cancers (significant excess bleeding risk vs. other solid tumours). Thrombocytopaenia from haematological malignancies or bone marrow suppression. Additional risk factors: advancing age, renal/hepatic impairment, metastatic disease, low BMI, treatment with ibrutinib, VEGFi, cetuximab, or bevacizumab.
• Gastric protection: Routine PPI use should be considered in all cancer patients on DAPT or anticoagulation.
• Antiplatelet therapy:
  • Bleeding risk ~1.6× greater than non-cancer patients following ACS/PCI. Risk greatest within 1 year of cancer diagnosis.
  • PRECISE-DAPT score performs poorly in cancer patients for predicting bleeding.
  • Minimize DAPT duration and intensity; avoid triple therapy when possible.
  • Thrombocytopaenia thresholds: Aspirin: platelets >10,000/µL. DAPT (aspirin + clopidogrel): >30,000/µL. Clopidogrel preferred over prasugrel/ticagrelor if platelets <50,000/µL. Avoid GP IIb/IIIa inhibitors if <50,000/µL.
  • PCI via radial approach preferred. Prophylactic platelet transfusion for platelets <20,000/µL.
• Bleeding management: Control source; platelet transfusion for thrombocytopaenia; withhold/reverse anticoagulation for life-threatening bleeding. Antifibrinolytics (tranexamic acid, ε-aminocaproic acid) can be considered. NOAC-specific reversal agents for life-threatening bleeding. Avoid recombinant activated factor VII or activated PCC in patients with recent thrombosis.

Peripheral Artery Disease in Cancer (Section 6.8)

• Cancer therapy increases arterial stiffness (meta-analysis: both anthracycline and non-anthracycline treatment).
• Raynaud phenomenon: Associated with bleomycin, cyclophosphamide, platinum compounds, vinca alkaloids, fluoropyrimidines. Treatment: avoidance of provoking factors (cold, vasoconstricting drugs) + long-acting dihydropyridine CCB (amlodipine, modified-release nifedipine).
• Nilotinib and ponatinib: Increased risk of vascular adverse events including arterial stiffness and PAD. Can be severe/life-threatening. Ponatinib arterial occlusive disease is dose-related. Screen for pre-existing PAD and vascular risk factors (DM) before and during therapy.
• If rapidly progressive PAD with second-generation TKI → switch to lower-risk TKI (e.g. imatinib). Antiplatelet agents or anticoagulation + statins should be considered. Correct all risk factors.
• Paraneoplastic acral vascular syndrome described after nivolumab (onset ~3 weeks).
• New symptomatic PAD: MDT approach regarding continue vs. interrupt culprit cancer therapy (Class I/C).

Pulmonary Hypertension in Cancer (Section 6.9)

• All five PH groups can occur in cancer patients:
  • Group 1 (PAH): Carfilzomib, bosutinib, dasatinib, ponatinib, interferon-alpha, alkylating agents (mitomycin C, cyclophosphamide — mostly cause pulmonary veno-occlusive disease).
  • Group 2 (left heart disease): Drugs causing HF (e.g. anthracyclines).
  • Group 3 (lung disease): Drugs causing pulmonary fibrosis (bleomycin, thoracic radiation).
  • Group 4 (chronic thromboembolic): VTE (most common pulmonary vascular complication of cancer); central venous catheters; tumour obstruction (angiosarcoma, renal/uterine carcinoma, testicular germ cell tumours).
  • Group 5 (multifactorial): Pulmonary tumour micro-embolism; myeloproliferative disorders (spleen enlargement, Budd-Chiari syndrome, extramedullary haematopoiesis).
• Dasatinib-induced PAH — specific management:
  • DASISION trial: 5% with dasatinib vs. 0.4% with imatinib developed PH.
  • Peak TRV >3.4 m/s (estimated sPAP ≥50 mmHg): Right-heart catheterization + dasatinib discontinuation recommended (Class I/C).
  • New asymptomatic TRV 2.9–3.4 m/s: Dasatinib dose reduction + close TRV monitoring with TTE every 4 weeks (Class IIa/C). If TRV normalises → continue with reduced monitoring (q3 months). If TRV continues to rise → right-heart catheterization, stop dasatinib, consider PAH drugs if confirmed.
  • Confirmed dasatinib-induced PAH or asymptomatic TRV >3.4 m/s: Switch to alternative BCR-ABL inhibitor after TRV recovery to <2.8 m/s (Class I/C).
• Overall PH management per 2022 ESC/ERS PH guidelines; referral to PH centre for MDT with oncology.

Pericardial Diseases in Cancer (Section 6.10)

• Pericarditis and pericardial effusion can be caused by: chest radiation, cytotoxic therapies (anthracyclines, bleomycin, cyclophosphamide, cytarabine), targeted therapies (all-trans retinoic acid, arsenic trioxide, dasatinib), and immune-based therapies (IL-2, interferon-α, ICI). Combinations may have synergistic pericardial effects.
• Must differentiate from progressive cancer (local invasion, metastatic involvement, lymphatic obstruction) and infection (especially in immunocompromised).

Pericarditis

• Diagnosis follows same principles as non-cancer patients but symptoms may be atypical.
• Radiation-induced acute pericarditis: Rare with modern techniques; occurs within days–weeks; usually self-limiting but may evolve to constrictive pericarditis years later.
• Treatment: Anti-inflammatory drugs (ibuprofen) + colchicine (reduces recurrence requiring repeat intervention) (Class I/C). Low-to-moderate dose steroids only for resistant cases, except ICI-related pericarditis.
• ICI-associated pericarditis: Median onset 30 days; poor prognosis especially with concomitant myocarditis.
  • Severe (moderate/severe effusion): ICI discontinuation (Class I/C) + high-dose steroids (methylprednisolone 1 mg/kg/day) ± colchicine. Pericardiocentesis for tamponade. Immunosuppressive drugs for refractory cases.
  • Uncomplicated: ICI may continue; consider colchicine or NSAIDs.
  • ICI restart: MDT discussion after resolution of pericardial disease, under close monitoring.

Pericardial Effusion

• Cancer therapy causes <30% of pericardial effusions in cancer patients (may increase with ICI expansion). Malignancy-related effusions (lung, oesophageal, breast, haematological, ovarian, melanoma) generally carry poor prognosis.
• Malignant effusions account for >30% of cardiac tamponade cases; usually develop slowly → larger effusions at diagnosis.
• Management: Small-to-medium (>4 and <20 mm): monitor at 7–14 days then 4–6-weekly. Tamponade: immediate echo-guided pericardiocentesis preferred over surgical pericardiotomy (Class I).
• Surgical pericardial window should be considered if percutaneous approach not feasible, or for recurrent malignant effusions after emergency pericardiocentesis (Class IIa/C).
• Intrapericardial instillation of cytostatic/sclerosing agents may be considered for recurrence prevention (Class IIb/C).
• Colchicine may improve outcomes and reduce repeat intervention in malignant tamponade.

End-of-Therapy CTRCD Management (Section 7.3)

• Full recovery criteria defined: No HF symptoms + LVEF >50% + GLS within normal range (or baseline) + cardiac serum biomarkers within normal range (or baseline).
• Weaning HF medications — candidate selection:
  • Low-risk for weaning: Low/moderate baseline CV toxicity risk (HFA-ICOS), no pre-existing CV medication indications, cancer treatment associated with generally reversible myocardial damage, asymptomatic mild CTRCD, early recovery (3–6 months), no family history of cardiomyopathy → consider weaning after MDT (Class IIa). Most common scenario: trastuzumab-only CTRCD in younger HER2+ BC survivors without anthracycline exposure.
  • High-risk — continue long-term HF therapy: Baseline high/VH risk, pre-existing indications for CV meds, irreversible-type drug exposure, severe/very severe CTRCD, slow or incomplete LV recovery, family history of cardiomyopathy (Class I).
• Post-weaning monitoring: Reassess LV function with TTE and cardiac biomarkers after withdrawal to ensure cardiac function remains normal.
• Patients on any CV therapy for CTR-CVT: Clinical assessment + ECG + echo + biomarkers at 3, 6, and 12 months after completing cancer treatment.

Cardiopulmonary Fitness and Rehabilitation (Section 7.4–7.5)

• Low CRF is an independent predictor of all-cause, cancer-related, and CVD-related mortality in cancer survivors. 14% decrease in CVD mortality per 1 MET (3.5 mL O₂/kg/min) increase in CRF.
• CPET may be considered in cancer survivors with exercise intolerance at 12 months + normal resting echo and biomarkers (Class IIb/C).
• Targeted cardiac rehabilitation should be considered in cancer survivors with high CV risk (Class IIa/B).
• Supervised exercise (including HIIT) is safe and well tolerated; attenuates CTR-CVT risk and improves CRF, fatigue, and quality of life. HIIT may not be feasible in elderly/frail patients.

Long-Term Follow-Up — Cancer Survivors (Section 8)

• End-of-treatment assessment (within 1 year of completing cardiotoxic therapy): Class I for all. Reassess LVEF, GLS, biomarkers, and CVRF.
• Long-term surveillance stratification:
  • Low risk: Annual CV risk assessment + CVRF management
  • Moderate risk: Cardiology referral at 1 year + TTE every 5 years
  • High/VH risk: Cardiology referral at 3 months + 1 year; TTE at years 1, 3, 5, then every 5 years
• Cardiac rehabilitation in cancer survivors improves cardiorespiratory fitness and quality of life (Class IIa).
• Long-term complications of anthracycline and mediastinal radiotherapy include coronary artery disease, valvular disease (particularly aortic and mitral stenosis), pericardial disease, and delayed cardiomyopathy.
• Childhood cancer survivors: High-risk survivors warrant echocardiographic screening even when asymptomatic; cumulative anthracycline dose >250 mg/m² doxorubicin equivalent is a major risk indicator.

Special Populations (Section 9)

• Cardiac amyloidosis (AL-CA): Non-invasive algorithm (NT-proBNP + troponin elevation + CMR findings) for diagnosis and monitoring; VH risk category for multiple myeloma therapies.
• Cardiac implantable devices (CIED) and radiotherapy: Risk stratification based on device location relative to RT field; contingency protocols required; monitoring by device manufacturer recommended.
• Pregnancy in cancer: Anthracycline-based chemotherapy in pregnancy requires cardiac monitoring protocol; avoid non-essential cardiotoxic agents in 1st trimester.
• Carcinoid heart disease: 5-HIAA-guided surveillance; tricuspid/pulmonary valve involvement; surgery for severe symptomatic carcinoid valvular disease.

Limitations of the document

• Majority of recommendations are Level of Evidence C (consensus of expert opinion) — dedicated cardio-oncology RCT evidence is sparse.
• HFA-ICOS risk tools require prospective validation; current tools are retrospective and cancer-type-specific.
• The rapidly evolving oncology treatment landscape (new targeted agents, immunotherapy combinations) means some drug-specific protocols may lag behind approvals.
• CHA2DS2-VASc score has limited validation in cancer populations; cancer itself increases thromboembolic risk beyond what the score captures.
• Most data on CTR-CVT come from adult patients; childhood/adolescent-specific evidence is limited.
• Evidence on the optimal duration for weaning cardioprotective medications after CTRCD resolution is lacking.

Key Concepts Mentioned

• concepts/Cardio-Oncology — the new clinical discipline integrating cardiology and oncology
• concepts/Cancer-Therapy-Related-CV-Toxicity — CTRCD definitions, grading, monitoring, and management
• concepts/HFA-ICOS-Risk-Stratification — pre-treatment CV toxicity risk tool
• concepts/CHA2DS2-VA — stroke risk score; note: this guideline uses CHA2DS2-VASc (older version); updated by ESC 2024 AF guidelines
• concepts/Late-Gadolinium-Enhancement — CMR for CTRCD and ICI myocarditis diagnosis
• concepts/HFpEF — CTRCD may manifest as HFpEF phenotype
• concepts/Genetic-Testing-in-AF — genetic susceptibility to CTR-CVT noted as future research need

Key Entities Mentioned

• entities/Atrial-Fibrillation — AF in cancer: epidemiology, anticoagulation (TBIP), rate control; BTK inhibitor-associated AF
• entities/Heart-Failure — CTRCD management; HF therapies repurposed as cardioprotection; CAR-T CRS-related HF
• entities/DCM — anthracycline-induced cardiomyopathy overlaps with DCM phenotype
• entities/LMNA — genetic predisposition to CTR-CVT noted (family history of premature CVD/genetic CVD)

Wiki Pages Updated

• Created: wiki/sources/Cardio-Oncology-ESC-2022.md
• Created: wiki/concepts/Cardio-Oncology.md
• Created: wiki/concepts/Cancer-Therapy-Related-CV-Toxicity.md
• Updated: wiki/entities/Atrial-Fibrillation.md (AF in cancer section)
• Updated: wiki/entities/Heart-Failure.md (CTRCD and cardio-oncology section)
• Updated: wiki/wikiindex.md
• Updated: log.md
• Updated: wiki/concepts/Cancer-Therapy-Related-CV-Toxicity.md, wiki/entities/Heart-Failure.md (expanded CTRCD management — anthracycline severity-stratified, HER2 permissive continuation, rechallenge strategies, HF pharmacotherapy tiers, end-of-therapy weaning criteria, cardiac rehab/CRF)
• Updated: wiki/concepts/Cancer-Therapy-Related-CV-Toxicity.md, wiki/entities/Atrial-Fibrillation.md (added CAD (ACS + CCS), fluoropyrimidine cardiotoxicity, ICI myocarditis management, Takotsubo, VHD, CAR-T complications, BTK inhibitors, ADT CV toxicity, pericardial diseases, pulmonary hypertension, PAD, bleeding complications)
• Reorganised: wiki/sources/Cardio-Oncology-ESC-2022.md (template format fix; section order aligned to source document chapters 2–9)
• Expanded: wiki/sources/Cardio-Oncology-ESC-2022.md sections 5.1–5.4 (general prevention principles, primary/secondary prevention, surveillance methodology — biomarkers and cardiac imaging); sections 5.5.1–5.5.18 (drug-specific monitoring for all 18 treatment categories); section 6.1.5 (HF during HSCT)
• Updated: wiki/concepts/Cancer-Therapy-Related-CV-Toxicity.md (monitoring methodology section 5.4; primary prevention strategies section 5.2 with named agents; drug-specific monitoring highlights for all 18 drug classes)
• Updated: wiki/entities/Heart-Failure.md (HSCT-related HF section 6.1.5 — CV complications during HSCT, management per ESC guidelines, ACE-I + BB evidence, post-HSCT exercise, prehabilitation)