HFA-ICOS cardio-oncology baseline risk assessment prior to cardio-toxic anti-cancer therapy

The HFA-ICOS cardio-oncology tools were developed to risk stratify oncology patients prior to commencing potentially cardio-toxic anti-cancer therapy.

The tools were developed in 2020 by the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society (HFA-ICOS) (1).

The tools stratify oncology patients before starting treatment into very high, high, moderate and low risk for cardiovascular complications according to the therapy planned. Based on this information, a personalised approach to risk factor modification and surveillance can be taken.

The risk stratification tools were developed following a workshop organised by cardio-oncology study group of the HFA in collaboration with ICOS. The tools are based on literature evidence and expert opinion and reflect the consensus opinion of HFA-ICOS. Prospective validation of the tools is ongoing.

The risk stratification tools cover 7 classes of cardio-toxic anti-cancer therapy, based on therapy and patient related factors contributing to cardiovascular risk.

The risk level according to therapy is calculated as follows:
Low risk: No risk factors or one medium¹ risk factor
Moderate risk: Medium risk factor points totalling 2-4. E.g. one medium² risk factor or 2 medium¹ risk factors.
High risk: One or more high risk factor or medium risk factors points totalling 5 or more
Very high: One or more very high risk factor

The guidelines recommend the following general principles according to risk score:
Low risk: Continue treatment with appropriate cardiovascular surveillance.
Medium risk: Requires closer monitoring of cardiovascular health. Consider cardio-oncology or cardiology referral.
High and very high risk: Refer for cardio-oncology or cardiology assessment, to optimise risk factors and provide a personalised management plan.

The HFA-ICOS risk stratification tools are also recommended in the latest European Society of Cardiology (ESC) cardio-oncology guidelines 2022 (2) to determine pre-treatment risk of cancer treatment related cardiovascular toxicity (CT-CVT). The ESC guidelines propose surveillance and management pathways according to baseline risk and planned treatment.

Details of the risk scoring for each type of therapy are provided below.

Anthracycline chemotherapy:

Very high risk factors:
Heart failure or cardiomyopathy.

High risk factors:
Myocardial infarction or previous coronary revascularisation, stable angina, severe valvular heart disease, baseline LVEF <50%, age≥ 80 years, previous anthracycline exposure, prior radiotherapy to the left chest or mediastinum.

Medium risk factors (2 points each):
Borderline LVEF of 50-54%, age 65-79 years.

Medium risk factors (1 point each):
Elevated baseline troponin, elevated baseline BNP or NT-proBNP, hypertension, diabetes mellitus, chronic kidney disease, previous non-anthracycline based chemotherapy, current smoker or significant history, obesity.

HER2 targeted therapies

Very high risk factors:
Heart failure or cardiomyopathy, prior trastuzumab cardio-toxicity

High risk factors:
Myocardial infarction or CABG, stable angina, severe valvular heart disease, baseline LVEF <50%, age≥ 80 years.

Medium risk factors (2 points each):
Borderline LVEF of 50-54%, arrhythmia, elevated baseline troponin, elevated baseline BNP or NT-proBNP, age 65-79 years, prior remote anthracycline exposure, prior radiotherapy to the left chest or mediastinum.

Medium risk factors (1 point each):
Hypertension, diabetes mellitus, chronic kidney disease, current regimen includes anthracycline prior to HER2 therapy, current smoker or significant history, obesity.

VEGF inhibitors

Very high risk factors:
Heart failure or cardiomyopathy, arterial vascular disease.

High risk factors:
Venous thrombosis, baseline LVEF <50%, QTc≥ 480ms, age≥ 75 years, hypertension, prior anthracycline exposure.

Medium risk factors (2 points each):
Borderline LVEF of 50-54%, 450ms≥ QTc < 480ms (men), 460ms≥ QTc < 480ms (women), arrhythmia.

Medium risk factors (1 point each):
Elevated baseline troponin, elevated baseline BNP or NT-proBNP, age 65-74, diabetes mellitus, chronic kidney disease, proteinuria, hyperlipidaemia, prior radiotherapy to left chest or mediastinum, current smoker or significant history, obesity.

Combination RAF and MEK inhibitors

Very high risk factors:
Heart failure or cardiomyopathy.

High risk factors:
Myocardial infarction or CABG, stable angina, severe valvular heart disease, prior anthracycline exposure.

Medium risk factors (2 points each):
Borderline LVEF of 50-54%, elevated baseline troponin, elevated baseline BNP or NT-proBNP, hypertension, prior radiotherapy to left chest or mediastinum.

Medium risk factors (1 point each):
Arrhythmia, age ≥ 65 years, diabetes mellitus, chronic kidney disease, current smoker or significant history, obesity.

Multi-targeted kinase inhibitors for CML

Very high risk factors:
Arterial vascular disease, arterial thrombosis with TKI.

High risk factors:
Heart failure or LVSD, BCR-ABL TKI mediated LVSD, abnormal ABPI, pulmonary arterial hypertension, baseline LVEF <50%, QTc≥ 480ms, cardiovascular disease risk score of > 20%, age ≥ 75 years, current smoker or significant history.

Medium risk factors (2 points each):
Venous thromboembolism, arrhythmia, QTc < 480ms (men), 460ms≥ QTc < 480ms (women), hypertension, age 65-74 years.

Medium risk factors (1 point each):
Diabetes mellitus, hyperlipidaemia, age ≥ 60 years < 65, chronic kidney disease, family history of thrombophilia, obesity.

Multiple myeloma therapies

Very high risk factors:
Heart failure or cardiomyopathy, prior proteosome inhibitor cardiotoxicity, venous thrombosis, cardiac amyloidosis, arterial vascular disease.

High risk factors:
Prior immunomodulatory drug cardiovascular toxicity, baseline LVEF <50%, elevated baseline BNP or NT-proBNP, age≥ 75 years, prior anthracycline exposure.

Medium risk factors (2 points each):
Borderline LVEF of 50-54%, arrhythmia, elevated baseline troponin.

Medium risk factors (1 point each):
Left ventricular hypertrophy, age 65-74 years, hypertension, diabetes mellitus, hyperlipidaemia, chronic kidney disease, family history of thrombophilia, prior spine radiotherapy, high dose dexamethasone >160mg/month, current smoker or significant history, obesity.

References:

1. Lyon AR, Dent S, Stanway S, et al. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society. Eur J Heart Fail. 2020;22(11):1945-1960. doi:10.1002/ejhf.1920
2. Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244