2022 ESC Guidelines on Cardio-Oncology

What's New in the 2022 Guidelines

The 2022 ESC Cardio-Oncology Guidelines represent the first comprehensive European guidance on managing cardiovascular disease in cancer patients. This guideline contains 272 new recommendations addressing the full spectrum of cancer therapy-related cardiovascular toxicity (CTR-CVT).

Key Innovations

New international definition of cancer therapy-related cardiac dysfunction (CTRCD)
Risk stratification framework for all major cancer therapies
Integration of cardio-oncology into mainstream cardiology practice
Evidence-based recommendations for monitoring and intervention strategies
Special populations: childhood survivors, pregnant women, CIED patients

Baseline Cardiovascular Risk Assessment

Cardiovascular toxicity risk stratification before starting potentially cardiotoxic anticancer therapy is Class I in all patients with cancer.

Risk Assessment Tools

SCORE2/SCORE2-OP: Recommended for estimating 10-year fatal and non-fatal CVD risk in patients without pre-existing CVD.

Baseline Cardiac Imaging: Transthoracic echocardiography (TTE) is recommended as the first-line modality for all patients. 3D echocardiography is preferred for LVEF measurement.

Biomarkers: Baseline measurement of natriuretic peptides (NP) and cardiac troponin (cTn) is recommended in high- and very high-risk patients.

Baseline Testing Recommendations

Test	Recommendation	Class	Evidence
CV risk stratification	All patients before starting therapy	I	B
Electrocardiogram	All patients starting cancer therapy	I	C
Echocardiography	First-line modality for cardiac assessment	I	C
3D Echocardiography	Preferred for LVEF measurement	I	B
Biomarkers (NP/cTn)	High- and very-high-risk patients	I	B

CTRCD Definition and Grading

Cancer therapy-related cardiac dysfunction (CTRCD) is a new international definition developed to standardize diagnosis and management across the cancer care continuum.

Definition

CTRCD Diagnostic Criteria

Decrease in LVEF ≥10 percentage points from baseline

LVEF after therapy falls to <50%

Grading of CTRCD

Grade	LVEF Reduction	Symptoms	Management
Asymptomatic	≥10% decline, <50%	None	Consider HF therapy; close monitoring
Mild Symptomatic	≥10% decline, <50%	NYHA I-II	HF therapy (ACE-I/ARB, beta-blocker)
Moderate Symptomatic	≥10% decline, <50%	NYHA II-III	Multidisciplinary approach; temp interruption if severe
Severe Symptomatic	≥10% decline, <40%	NYHA III-IV	Discuss cancer therapy discontinuation; intensive HF therapy

Monitoring Strategy

All patients with cancer should have risk-stratified cardiac monitoring. The frequency and intensity of monitoring depend on baseline CV risk, type of cancer therapy, and cumulative doses.

Anthracycline Cardiotoxicity

Anthracyclines are among the most cardiotoxic cancer therapies. Dose-dependent myocardial damage can occur acutely, early, or late after treatment.

Risk Factors

High-Risk Patients for Anthracycline Cardiotoxicity

Cumulative anthracycline dose >240 mg/m²
Age <5 years or >60 years at treatment
Female sex
Pre-existing cardiovascular disease
Uncontrolled hypertension or diabetes
Concurrent or prior cardiotoxic therapy (HER2 inhibitors, RT)

Baseline and Monitoring Recommendations

Timing	Assessment	Frequency (High-Risk)
Baseline	TTE, ECG, biomarkers (NP, cTn)	Before therapy
During therapy	Echocardiography	Every 2 cycles and within 3 months post-therapy
Post-therapy	Echocardiography	Within 12 months in all patients
Biomarkers	NP and cTn monitoring	Every cycle (high-risk) and 3, 12 months post

Management of Anthracycline-Induced CTRCD

Recommended Approaches

HF therapy with ACE-I/ARBs and beta-blockers for symptomatic CTRCD
Temporary interruption of anthracycline therapy for symptomatic CTRCD with LVEF <50%
Multidisciplinary discussion before restarting therapy in patients with CTRCD
Cardioprotective therapy continuation during cancer treatment when possible

Not Recommended

Automatic discontinuation without multidisciplinary assessment
Delaying cancer therapy initiation without clear CV contraindications

HER2-Targeted Therapy Cardiotoxicity

HER2-targeted therapies including trastuzumab, pertuzumab, and T-DM1 can cause reversible cardiac dysfunction. Unlike anthracyclines, HER2-related cardiotoxicity is typically non-dose-dependent.

Baseline Assessment

Class I Baseline echocardiography and NP/cTn measurement are recommended before HER2-targeted therapy initiation in all patients.

Monitoring During Treatment

HER2-Targeted Therapy Monitoring Schedule

Every 3 months during treatment

Within 12 months after completing treatment

Every 6 months if asymptomatic without CV toxicity

Management Decisions

Clinical Scenario	Recommendation	Class
Symptomatic moderate-severe CTRCD (LVEF <50%)	HF therapy recommended; temporary interruption with improvement then restart	I
Asymptomatic CTRCD (LVEF 40-50%)	HF therapy and multidisciplinary discussion for continuation	I
Mild symptomatic CTRCD	HF therapy with decision to continue vs. interrupt after LV improvement	I

Immune Checkpoint Inhibitor (ICI) Myocarditis

ICI-associated myocarditis is a rare but potentially fatal adverse effect. Early diagnosis and aggressive immunosuppression are critical for patient survival.

Clinical Presentation

Timing: Can occur at any point during ICI therapy, even months after initiation.

Symptoms: Chest pain, dyspnea, palpitations, syncope, cardiogenic shock.

Risk Factors: Prior myocarditis, autoimmune disease, concurrent ICI therapies.

Diagnostic Approach

Class I cTn, ECG, and CV imaging (echocardiography and/or CMR) are recommended to diagnose ICI-associated myocarditis.

Management Algorithm

ICI-Associated Myocarditis Management

Temporary interruption of ICI treatment until diagnosis confirmed/refuted

Early high-dose corticosteroids for confirmed myocarditis

ICU admission (level 3) for hemodynamically unstable patients

Mechanical support if indicated (ECMO, VAD)

Restart ICI only after complete recovery with cardiology consensus

Key Management Points

Do's

Suspect ICI myocarditis in any cancer patient presenting with acute chest pain and biomarker elevation during ICI therapy
Obtain ECG, cTn, and imaging immediately
Interrupt ICI therapy pending confirmation
Initiate high-dose corticosteroids and immunosuppression early
Monitor closely in ICU setting with continuous telemetry

Don'ts

Delay diagnostic workup or immunosuppressive therapy
Restart ICI therapy without complete resolution of myocarditis
Manage in non-ICU settings if hemodynamically unstable

VEGF Inhibitor-Induced Hypertension

VEGF inhibitors (bevacizumab, sunitinib, sorafenib, ramucirumab) frequently cause treatment-emergent hypertension through endothelial dysfunction and reduced nitric oxide availability.

Blood Pressure Monitoring

Class I BP measurement is recommended for patients treated with VEGF inhibitors at every clinical visit. Daily home monitoring is recommended during the first cycle, after each VEGF dose increase, and every 2-3 weeks thereafter.

Pharmacological Management

Medication Class	Recommendation	Notes
ACE-I or ARB	First-line antihypertensive drugs	Preferred for VEGF-HTN
Dihydropyridine CCB	Second-line for uncontrolled BP	Safe with VEGF inhibitors
Diuretics	Not recommended	Due to drug-drug interactions
Verapamil	Not recommended	CYP3A4 interactions

ECG and QTc Monitoring

For patients treated with VEGF inhibitors at moderate or high risk of QTc prolongation, ECG monitoring is recommended monthly during the first 3 months and every 3-6 months thereafter.

QTc Prolongation in Cancer Therapy

Multiple targeted cancer therapies prolong the QT interval, increasing the risk of torsades de pointes and sudden cardiac death.

High-Risk Drugs

Tyrosine Kinase Inhibitors: Sunitinib, sorafenib, pazopanib, vandetanib

Cyclin-Dependent Kinase 4/6 Inhibitors: Ribociclib

ALK/EGFR Inhibitors: Crizotinib, alectinib

Others: Arsenic trioxide, tyrosine kinase inhibitors

Baseline and Monitoring Requirements

Class I QTc monitoring at baseline and day 14-28 in all patients receiving QTc-prolonging cancer therapy.

Risk Level	Baseline QTc	Monitoring Frequency
Moderate QTc prolongation	ECG, electrolytes	Monthly × 3 months, then every 3-6 months
High QTc prolongation	ECG, electrolytes, baseline BNP	More frequent (per drug guidance)
After dose increase	12-lead ECG recommended	Within 1-2 weeks

Management of QTc Prolongation

QTc Management Algorithm

QTcF <480 ms: Continue therapy with monitoring

QTcF 480-500 ms: Repeat ECG, correct electrolytes, consider dose reduction

QTcF >500 ms: Temporary interruption until <480 ms

Sustained VT or TdP: Discontinuation recommended

Venous Thromboembolism in Cancer Patients

Cancer patients have markedly elevated VTE risk. Thromboprophylaxis with anticoagulation is critical across the cancer care continuum.

Prophylaxis Recommendations

Class I Apixaban, edoxaban, or rivaroxaban are recommended for treatment of symptomatic or incidental VTE in patients without contraindications.

LMWH Dosing for Cancer Patients

Class I LMWH are recommended for treatment of symptomatic or incidental VTE in patients with cancer with platelet count >50,000/μL.

Prophylactic Anticoagulation

Clinical Scenario	Recommendation	Class
Hospitalized cancer patients	Prophylactic LMWH for ≥4 weeks post-operatively (surgical patients)	I
Catheter-associated VTE	Minimum 3 months anticoagulation; continue >3 months if catheter in place	I
Major bleeding prophylaxis	Extended LMWH × 4 weeks post-op for high VTE/high bleed risk	I

Radiation-Induced Heart Disease

Cardiac radiation therapy (RT) causes late cardiovascular complications including coronary artery disease, valvular heart disease, pericarditis, and cardiomyopathy.

Risk Stratification

Baseline cardiovascular risk assessment and estimation of 10-year fatal and non-fatal CVD risk with SCORE2 or SCORE2-OP is recommended in all patients receiving RT to a volume including the heart.

Cardiac Imaging Prior to Potentially Cardiotoxic Therapies

Class I Baseline comprehensive TTE is recommended in all patients with cancer at high-risk and very high-risk of CV toxicity before starting anticancer therapy.

Post-RT Surveillance

Long-Term Monitoring Strategy

Regular clinical evaluation for CV symptoms
Annual CVRF assessment and aggressive modification
Periodic echocardiography based on symptomatology and CVRF
Stress testing or CT angiography for suspected coronary disease

CAR-T Cell Therapy and TIL Therapy Cardiotoxicity

Chimeric antigen receptor T-cell (CAR-T) therapy can cause severe myocarditis and cytokine release syndrome (CRS) with potential CV collapse.

Baseline Assessment

Class I Baseline ECG, NP, cTn, and echocardiography are recommended in all patients before starting CAR-T and TIL therapies.

Pre-Existing CVD Evaluation

Class I A baseline echocardiography is recommended in patients with pre-existing CVD before starting CAR-T and TIL therapies.

CRS Monitoring and Management

CRS Grade Assessment (ASCT Scale ≥2)

Measurement of NP, cTn, and echocardiography recommended

Continuous hemodynamic monitoring in ICU setting

Vasopressor support and mechanical support as needed

Tocilizumab and/or corticosteroids for CRS management

Long-Term Survivorship and Monitoring

Cancer survivors treated with cardiotoxic therapies require structured long-term CV follow-up to detect and manage late complications.

Asymptomatic Adult Survivors

Class I Annual CV risk assessment, NP and cTn measurement, and CVRF management are recommended in cancer survivors treated with potentially cardiotoxic drugs or RT.

Timing Post-Therapy	Assessment	Frequency
First year post-therapy	CVRF assessment, echocardiography (if symptomatic)	3, 12 months
Asymptomatic (baseline normal)	Biomarkers, clinical assessment	Annually
New cardiac symptoms	Echocardiography, biomarkers, stress testing	As indicated

Childhood Cancer Survivors

Class I Education of adults who were childhood/adolescent cancer survivors regarding their increased CV risk and recognition of early CV symptoms is recommended.

Pregnancy Considerations

Class I For female cancer survivors considering pregnancy, baseline CV evaluation including history, physical examination, ECG, NP, and echocardiography is recommended.

Key Do's and Don'ts

Do's

Perform baseline CV risk stratification in all patients before starting potentially cardiotoxic cancer therapy
Use risk-stratified monitoring protocols tailored to cancer therapy type and patient risk
Implement CVRF management per 2021 ESC CVD Prevention Guidelines
Initiate HF therapy early for asymptomatic and symptomatic CTRCD
Use multidisciplinary approach for cancer therapy discontinuation decisions in CTRCD
Provide patient education on CV risks, symptoms, and lifestyle modifications
Establish long-term CV follow-up plans before cancer therapy completion
Document CV risk and baseline findings clearly in patient records

Don'ts

Don't delay cancer therapy initiation without clear CV contraindications
Don't use generic monitoring schedules—tailor to individual risk and therapy type
Don't ignore asymptomatic LVEF decline; intervene with HF therapy early
Don't manage ICI myocarditis without ICU admission and immunosuppression
Don't recommend diuretics or verapamil for VEGF inhibitor-induced HTN
Don't skip baseline ECG and biomarker assessment in high-risk patients
Don't manage cancer therapy-CV complications in isolation; use integrated approach
Don't discontinue cardioprotective therapies without multidisciplinary input

Risk Assessment Calculators and Tools

The following calculators and tools support CV risk stratification and monitoring in cancer patients:

SCORE2 Calculator

Estimate 10-year fatal and non-fatal CVD risk in cancer patients without pre-existing CVD

SCORE2-OP Calculator

Calculate CVD risk for older adults (≥70 years) with cancer

TIMI Risk Score

Assess acute coronary syndrome risk in cancer patients with chest pain

ESC HF Risk Score

Estimate heart failure risk in cancer survivors

Framingham CVD Risk

Alternative CVD risk prediction for 10-year event estimation

LVEF Monitoring Tracker

Track LVEF changes over time and calculate percentage decline

Using These Tools in Practice

SCORE2/SCORE2-OP: Use at baseline to stratify all cancer patients into risk categories (low, moderate, high, very high).

LVEF Tracker: Document baseline and serial LVEF measurements to calculate percentage decline and determine CTRCD diagnosis.

Risk Scores: Apply during follow-up to reassess CV risk and guide intensity of monitoring.

Integration: Combine tools with clinical judgment, biomarkers, and imaging for comprehensive assessment.