What is the role of Area Under the Curve (AUC) in monitoring cardiac function with echocardiography (echo) for patients receiving cardiotoxic medications like doxorubicin?

Role of Area Under the Curve (AUC) in Monitoring Cardiac Function with Echocardiography for Patients on Cardiotoxic Medications

Echocardiography with tissue Doppler imaging and strain measurements is the preferred method for monitoring cardiac function in patients receiving cardiotoxic medications like doxorubicin, as it can detect early signs of left ventricular dysfunction before reduction in ejection fraction occurs. 1

Primary Monitoring Parameters

• Baseline assessment of systolic and diastolic cardiac function with Doppler echocardiography (DEcho) should be conducted before starting anthracyclines or monoclonal antibodies, especially in patients aged >60 years or with cardiovascular risk factors 1
• Left ventricular ejection fraction (LVEF) is the traditional parameter monitored during treatment, with a reduction of ≥20% from baseline or decline to <50% necessitating reassessment or discontinuation of therapy 1
• Tissue Doppler imaging parameters (E' wave, A' wave, S wave velocity) provide quantitative information on myocardial diastolic relaxation and systolic performance before LVEF changes occur 1

Advanced Echocardiographic Parameters

• Myocardial strain imaging (longitudinal, radial, and circumferential) should be performed with every echocardiographic assessment as it can detect early impairment of myocardial function before detectable changes in LVEF 2, 3
• Global longitudinal strain reduction of >10% from baseline is considered significant and may indicate early cardiotoxicity despite normal LVEF 4, 3
• The Tei index (myocardial performance index) can detect declines in LV function earlier in the course of treatment with anthracyclines than standard echocardiographic measurements 5

Monitoring Schedule

• For anthracyclines: Evaluate LVEF after administration of half the planned dose, after cumulative dose of doxorubicin 300 mg/m², epirubicin 450 mg/m², or mitoxantrone 60 mg/m² 1
• More frequent monitoring is recommended for patients aged <15 or >60 years after cumulative doses of doxorubicin 240 mg/m² or epirubicin 360 mg/m² 1
• Assessment before each anthracycline administration and at 3,6, and 12 months after completion of therapy 1
• For monoclonal antibodies: Periodic monitoring every 12 weeks, especially in patients previously treated with anthracyclines 1
• Long-term follow-up at 4 and 10 years after anthracycline therapy for patients treated at <15 years of age or with high cumulative doses 1

Biomarkers as Complementary Tools

• Troponin I can predict subclinical and clinical cardiac morbidity and mortality after anthracycline therapy, but requires multiple serial measurements 1
• B-type natriuretic peptide (BNP) reflects increased LV filling pressure and correlates with LV dysfunction in cancer patients treated with cardiotoxic therapy 1
• Consider baseline assessment of biomarkers with periodic measurements during therapy (troponin I: at end of chemotherapy, after 12,24,36, 72h and 1 month later; BNP: at end of infusion and after 72h) 1

Management of Detected Cardiotoxicity

• LVEF reduction of ≥20% from baseline despite normal function or LVEF decline <50% requires reassessment or discontinuation of therapy and frequent echocardiographic checks 1
• Aggressive medical treatment with ACE inhibitors and β-blockers should be initiated within 2 months from the end of anthracycline therapy for patients showing LV dysfunction, even if asymptomatic 1
• Cardiac MRI should be considered when echocardiography results are borderline or ambiguous, as it provides superior tissue characterization capabilities 6, 2

Common Pitfalls and Caveats

• Standard LVEF measurement has numerous limitations and may miss early cardiotoxicity; strain imaging is more sensitive for early detection 3
• Two-dimensional echocardiography may only detect LVEF changes of approximately 10%, which may be too late for effective intervention 1, 4
• Waiting for symptomatic heart failure before intervention significantly worsens prognosis; early detection and treatment is critical 1
• Patients with normal LVEF but abnormal strain parameters should be closely monitored as they may be at higher risk for developing clinical heart failure 4, 3