What are the guidelines for echocardiogram (echo) and cardiac surveillance during anthracycline-based chemotherapy for high-risk patients?

Cardiac Surveillance Guidelines for High-Risk Patients on Anthracycline Chemotherapy

For high-risk patients receiving anthracycline-based chemotherapy, baseline echocardiographic assessment with LVEF and strain imaging is mandatory, followed by serial LVEF monitoring after cumulative doxorubicin doses of 250 mg/m² and every 100 mg/m² thereafter, with cardiac biomarker measurements every 3-6 weeks throughout treatment. 1

Baseline Assessment Requirements

Imaging Evaluation

• Baseline transthoracic echocardiography with LVEF measurement is required before initiating anthracycline therapy, using quantitative 2D or 3D techniques to establish a reference point for serial monitoring 1
• Global longitudinal strain (GLS) imaging should be obtained at baseline when available, as decreased baseline GLS ≥-18% independently predicts cardiotoxicity development even in patients with normal LVEF 1, 2
• Diastolic function parameters must be assessed, including E/A ratio, deceleration time, and isovolumic relaxation time 1

Cardiac Biomarkers

• Baseline measurement of cardiac troponins (TnI or TnT) and BNP or NT-proBNP should be obtained in high-risk patients (those with pre-existing cardiovascular disease or receiving high anthracycline doses) 1
• A baseline ECG with QTc measurement using either Bazett or Fridericia method is mandatory 1

Serial Monitoring During Treatment

Echocardiographic Surveillance Schedule

The following LVEF reassessment schedule is recommended for asymptomatic patients: 1

• After cumulative doxorubicin dose of 250 mg/m² (or epirubicin 450 mg/m², mitoxantrone 60 mg/m²) 1
• After approximately each additional 100 mg/m² of doxorubicin beyond 250 mg/m² (or approximately 200 mg/m² of epirubicin) 1
• At the end of therapy, even if cumulative dose is <400 mg/m² 1

For patients aged <15 years or >60 years, more frequent monitoring is required after lower cumulative doses (doxorubicin 240 mg/m² or epirubicin 360 mg/m²) 1, 3

Cardiac Biomarker Monitoring

• Periodic measurement of TnI or TnT and BNP or NT-proBNP every 3-6 weeks or before each chemotherapy cycle using the same institutional laboratory with 99% upper limit of normal as the threshold 1
• If either cardiac biomarker becomes abnormal or the patient develops symptoms, immediate reassessment of LVEF with or without GLS using 2D/3D echocardiography or cardiac MRI is required 1

Critical Imaging Principles

Technical Requirements

• Use the same imaging modality at the same facility for all serial testing to minimize variability and ensure accurate comparison 1
• Highly reproducible, quantitative volumetric, non-irradiating imaging with quality control is essential (quantitative 2D and 3D echocardiography, or cardiac MRI) 1
• GLS imaging may be considered for serial LV systolic function monitoring when available 1

Thresholds for Intervention

LVEF-Based Decision Points

• LVEF reduction ≥20% from baseline (even if still in normal range) OR absolute LVEF decline to <50% requires immediate reassessment or discontinuation of therapy 1, 3
• LVEF <40% mandates treatment discontinuation 1
• LVEF between 40-50% with >10% decline from baseline requires holding treatment and repeat assessment in 3 weeks 1

Post-Treatment Surveillance

• Follow-up echocardiography at 3,6, and 12 months after completion of anthracycline therapy is recommended even in asymptomatic patients 1
• Long-term surveillance at 4 and 10 years after therapy is recommended for patients treated at age <15 years or those receiving high cumulative doses 1

Common Pitfalls to Avoid

Do not wait for symptomatic heart failure before intervening—early detection through biomarkers and imaging changes allows for timely cardioprotective therapy initiation, which significantly improves outcomes when started within 2 months of detecting dysfunction 1, 3

Do not rely solely on LVEF measurements—approximately 26% of patients without pre-existing cardiac disease develop cardiotoxicity, and changes in EF between baseline and low-dose anthracycline (area under curve 0.92) best predict functional cardiotoxicity 4

Do not use different imaging modalities or facilities for serial measurements—this introduces significant variability that can mask true changes in cardiac function 1

Baseline GLS ≥-18% identifies patients at 3.5-fold increased risk of cardiotoxicity (sensitivity 0.70, specificity 0.70) even with normal baseline LVEF, warranting more intensive monitoring 2