Table 2.

Baseline Cardiovascular Assessment of Patients Before Anthracycline-Based Chemotherapy

	Summary of Evidence	Clinical Practice Recommendations	Research Recommendations
Blood biomarkers
NT-proBNP35,64,66	•Few studies have examined the prognostic value of baseline NT-proBNP, and evidence supporting this metric as a stand-alone predictor is weak.	•Baseline NT-proBNP is recommended to detect interval change during treatment, which may indicate preclinical cardiotoxicity.	•Elevated baseline troponin is linked to higher levels during treatments but not directly to cardiotoxicity outcomes in the same studies. •Existing studies exclude high-risk individuals who might benefit most from baseline assessment. Further research into the predictive value of troponin and NT-proBNP in unselected patient cohorts is needed.
Cardiac troponin65,173	•There is conflicting evidence for the utility of routine cardiac troponin measurement for risk stratification or early detection of clinical cardiotoxicity.	•Baseline cardiac troponin may have some role in determining cardiotoxicity risk during treatment.
Genetic testing45,69, 70, 71	•More than 40 genetic polymorphisms are linked to increased susceptibility to anthracycline-related cardiotoxicity, with studies varying from focusing on pharmacogenetics and mechanisms to those examining cardiomyopathy-related variants and conducting GWASs targeting cardiotoxicity as the phenotype.	•Routine genetic testing is not currently recommended.	•Although a growing number of studies link biologically plausible genetic variants to anthracycline-induced cardiotoxicity, almost all lack appropriate validation data. •The incremental utility of genetic testing over standard clinical assessments remains to be conclusively demonstrated. •Identifying patient groups most likely to benefit from genetic testing is important and would allow for more effective resource allocation.
Cardiovascular imaging
LVEF25,64,65,173	•Good evidence to support the use of baseline LVEF as an indicator of cardiotoxicity.	•Measure baseline LVEF using 3D TTE or CMR as the initial choice for all patients before anthracycline treatment.	•Head-to-head comparisons of baseline LVEF using different modalities and measurement methods to establish reproducibility, performance, and the prospective association with cardiotoxicity events.
GLS 25,64,65,173	•Good evidence to support GLS as an indicator of cardiotoxicity, with some evidence suggesting that GLS may detect cardiotoxicity onset before a decline.	•For all patients, measure baseline LVEF using 2D echocardiogram with 3 long-axis views before anthracycline treatment.	•In addition to the previous recommendation, assess the impact of variations in GLS by modality and vendor and the incremental value of this metric over LVEF in terms of translating to improved clinical outcomes.
Primary prevention
Reduce exposure164	•Reducing or omitting doses of anthracyclines is the most effective way to prevent related cardiotoxicity.	•Consider alternatives to anthracyclines when equally effective anticancer agents are available.	•The cumulative risk from anthracycline exposure is well-documented.
Cardioprotection (RAAS blockers, beta-blockers)80,81	•Existing evidence from multiple randomized trials does not support routine use of cardioprotection with RAAS blockers or beta-blockers.	•There is no evidence to support the routine use of pre-emptive cardioprotection with RAAS blockers or beta-blockers before anthracycline treatment.	•Most existing studies focus on low-risk cohorts; further research is needed to identify higher-risk patient subsets who may benefit from pre-emptive cardioprotection.
Liposomal doxorubicin73	•Multiple randomized trials support the protective role of liposomal doxorubicin in preventing incident cardiotoxicity compared with standard doxorubicin.	•Liposomal anthracyclines should be considered for patients at high and very high toxicity risk.	•Current research is limited to very select patient cohorts (considering malignancy type, status, and cardiotoxicity risk). The potential broader role of this drug in reducing risk beyond these contexts needs further exploration.
Dexrazoxane74,75,77	•Dexrazoxane has proven effective in reducing the risk of clinical heart failure in breast cancer patients receiving anthracycline chemotherapy.	•Dexrazoxane may be considered for high- or very high-risk patients for whom anthracyclines are essential.	•The use and role of dexrazoxane across different patient cohorts should be explored.
Exercise13, 14, 15, 16	•Animal models show a reduced risk of cardiotoxicity with exercise. In humans, exercise is linked to improved cardiorespiratory fitness metrics but has not been shown to reduce cardiotoxicity risk.	•There is inadequate evidence to recommend prescribed exercise specifically for reducing cardiotoxicity risk.	•Research should explore various exercise regimens in different cohorts, with better assessment of compliance (eg, using smart watch monitoring), and consider longer term outcomes.
Hypertension control174,175	•Observational studies in breast and hematologic cancer patients indicate a correlation between hypertension and an increased risk of AIC. Hypertension susceptibility loci are linked to AIC in childhood cancer survivors.	•Early control of blood pressure is recommended.	•Additional studies are necessary to further elucidate the mechanisms of hypertension and AIC comorbidity.

2D = 2-dimensional; AIC = anthracycline-induced cardiotoxicity; GWAS = genome-wide association study; NT-proBNP = N-terminal pro–B-type natriuretic peptide; RAAS = renin-angiotensin-aldosterone system; other abbreviations as in Table 1.