HFA-ICOS BCR-ABL baseline risk: how the risk level is set

The HFA-ICOS BCR-ABL proforma sorts a patient into a low, medium, high or very high baseline cardiovascular risk level before a second- or third-generation BCR-ABL kinase inhibitor for chronic myeloid leukemia (CML). Any very high factor sets very high. Otherwise any high factor, or 5 or more medium points, sets high. Medium points of 2 to 4 set medium, and anything less is low.

Not a medical device. Not a diagnosis or dosing recommendation.

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Hemodynamics calculators
Lyon AR et al. · 2020
The HFA-ICOS BCR-ABL logic
Worked examples
Frequently asked questions

What is the HFA-ICOS BCR-ABL risk tool?

BCR-ABL tyrosine kinase inhibitors (TKIs) are drugs for CML. Some of the newer ones are linked with heart and blood vessel problems. In 2020 the Heart Failure Association (HFA) Cardio-Oncology Study Group of the European Society of Cardiology and the International Cardio-Oncology Society (ICOS) published baseline risk proformas for several groups of cancer drugs, led by Lyon. This page covers the BCR-ABL proforma.

Magent's calculator takes age, sex, LVEF, QTc and the yes/no factors, and returns the risk level, the medium points and the paper's expert-opinion guide for that level.

This page explains the logic. It doesn't say what a risk level means for a particular person.

The HFA-ICOS BCR-ABL logic

very high   arterial vascular disease; arterial thrombosis with a BCR-ABL TKI
high        any high factor, or medium points ≥ 5
              high factors: heart failure or LV systolic dysfunction; TKI-mediated
              LV systolic dysfunction; ABPI ≤ 0.9; pulmonary arterial hypertension;
              LVEF < 50%; QTc ≥ 480 ms; 10-year cardiovascular risk > 20%;
              age ≥ 75; current or significant smoker
medium      medium points 2 to 4
low         medium points 0 or 1

medium points:
  2 each   venous thromboembolism; arrhythmia; borderline QTc
           (men 450 to < 480 ms, women 460 to < 480 ms); hypertension; age 65–74
  1 each   diabetes; hyperlipidemia; age 60–64; chronic kidney disease;
           family history of thrombophilia; obesity

Exact expression the calculator uses:

HFA-ICOS BCR-ABL TKI (Lyon 2020) = very_high if arterial_vascular_disease or arterial_thrombosis_with_tki; else high if any high factor or medium_points>=5; else medium if medium_points 2-4; else low (0 or one M1); medium_points = M2*2 + M1*1 only; High: heart_failure_or_lvsd, bcr_abl_tki_mediated_lvsd, abpi_le_0_9, pulmonary_arterial_hypertension, LVEF<50, QTc>=480, caller cvd_10y_risk_gt_20, age>=75, current_or_significant_smoker; M2: venous_thromboembolism, arrhythmia, borderline QTc (men 450<=QTc<480, women 460<=QTc<480), hypertension, age 65-74; M1: diabetes, hyperlipidemia, age 60-64, ckd, family_history_thrombophilia, obesity; age bands mutually exclusive; no LVEF 50-54 row; magent does not compute 10-year CVD risk

Inputs

Input	Meaning	Tier
`age_years`	Age in years	High at 75 or above; 2 points at 65 to 74; 1 point at 60 to 64
`sex`	Male or female, for the borderline QTc window	–
`lvef_percent`	Left ventricular ejection fraction, %	High below 50
`qtc_ms`	Corrected QT interval, ms	High at 480 or above; 2 points if borderline
`arterial_vascular_disease`, `arterial_thrombosis_with_tki`	Yes/no factors	Very high
`heart_failure_or_lvsd`, `bcr_abl_tki_mediated_lvsd`, `abpi_le_0_9`, `pulmonary_arterial_hypertension`, `cvd_10y_risk_gt_20`, `current_or_significant_smoker`	Yes/no factors	High
`venous_thromboembolism`, `arrhythmia`, `hypertension`	Yes/no factors	2 medium points each
`diabetes`, `hyperlipidemia`, `ckd`, `family_history_thrombophilia`, `obesity`	Yes/no factors	1 medium point each

How the calculation works

Check for very high. Arterial vascular disease or arterial thrombosis with a BCR-ABL TKI sets very high.
Check for high. Any high factor sets high.
Count medium points. Add 2 for each Medium 2 factor and 1 for each Medium 1 factor.
Set the level. 5 or more medium points is high, 2 to 4 is medium, and 0 or 1 is low.

Age uses one band at a time: 75 or above is high, 65 to 74 adds 2 points, 60 to 64 adds 1. Unlike the anthracycline proforma, this one has no 2-point row for an LVEF of 50 to 54%, and smoking is a high factor rather than a 1-point factor.

Units

Age is in years, LVEF in percent and QTc in milliseconds. The 10-year cardiovascular risk item is a yes/no answer; the calculator doesn't compute any 10-year risk equation. The guide figure returned with each level is a percentage band from the paper's expert opinion.

Worked examples

These use Magent's own expected values for the calculator.

Example 1: no factors

Age 50, LVEF 60%, QTc 400 ms, every factor no.
Medium points 0. Level: low. Guide: under 2%.

Example 2: age 62

Age 60 to 64 adds 1 medium point.
Medium points 1. Level: low. Guide: under 2%.

Example 3: age 70

Age 65 to 74 adds 2 medium points.
Medium points 2. Level: medium. Guide: 2–9%.

Example 4: current smoker

Smoking is a high factor on this proforma.
Medium points 0. Level: high. Guide: 10–19%.

Example 5: arterial vascular disease

Arterial vascular disease is a very high factor.
Medium points 0. Level: very high. Guide: 20% or more.

History of the HFA-ICOS proformas

The calculator cites Lyon and colleagues, European Journal of Heart Failure, 2020 (volume 22, issue 11, pages 1945–1960). The abstract describes a position statement from the HFA Cardio-Oncology Study Group of the European Society of Cardiology with the International Cardio-Oncology Society. Its baseline risk proformas cover several groups of cancer drugs, including second and third generation multi-targeted kinase inhibitors for CML targeting BCR-ABL, and sort patients into low, medium, high and very high risk of cardiovascular complications.

When it's used

The proforma describes a baseline risk level before a BCR-ABL kinase inhibitor starts.

Where it's used

The inputs come from the history, an ECG, an echocardiogram, blood tests and vascular measurements, gathered in hematology or cardio-oncology clinics.

Who uses it

The person using the calculator enters the measurements and yes/no factors. The calculator applies the proforma's rules.

Limits of the calculation

The calculator doesn't read an ECG or echocardiogram, measure the ankle-brachial pressure index, estimate pulmonary pressure or take a smoking history. Every input comes from the person entering it.
It doesn't compute a 10-year cardiovascular risk equation. That item is answered yes or no.
The guide percentages are the paper's expert opinion, not an absolute risk measured in a study.
The result is a baseline risk level. It isn't an order to start, hold or monitor a medicine, and this page doesn't say what to do with a level.

Clinical decisions belong to a qualified clinician who knows the patient.

HFA-ICOS anthracycline proforma comes from the same paper but uses a different factor list, with a 2-point LVEF row and smoking as a 1-point factor.
Framingham heart failure criteria describe heart failure itself. The HFA-ICOS proforma sets a baseline risk level before a cancer drug.
NYHA class grades symptoms in known heart failure.

Glossary

CML: chronic myeloid leukemia.
BCR-ABL TKI: a tyrosine kinase inhibitor that blocks the BCR-ABL protein driving CML.
QTc: the QT interval on an ECG corrected for heart rate.
ABPI: ankle-brachial pressure index, comparing blood pressure at the ankle and the arm.
LV systolic dysfunction (LVSD): reduced pumping of the left ventricle.

Common mistakes

Scoring smoking as 1 point. On this proforma it is a high factor.
Adding 2 points for an LVEF of 50 to 54%. This proforma has no such row.
Using the same QTc window for men and women. Borderline starts at 450 ms for men and 460 ms for women.
Stacking age bands. Age falls in one band.

Source

Lyon AR, 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. PMID: 32463967

Frequently asked questions

What sets very high risk on the BCR-ABL proforma?

Arterial vascular disease, or arterial thrombosis with a BCR-ABL kinase inhibitor.

Why is smoking a high factor on this proforma?

The paper lists current or significant smoking as a high factor for BCR-ABL inhibitors, unlike its anthracycline proforma.

Does the calculator compute 10-year cardiovascular risk?

No. That item is answered yes or no.

What is a borderline QTc here?

450 to under 480 ms for men and 460 to under 480 ms for women. It adds 2 medium points.

How many medium points make high risk?

5 or more.