Risk Prediction Models of Cardiotoxicity in Patients With Breast Cancer

Figures

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  Figure 1. Study Protocol Cardio-oncology surveillance, including echocardiography, 12-lead electrocardiogram (ECG), and biomarkers, was performed every 3 months (visits 0 to 4). Breast cancer treatment was categorized into 4 regimens: anthracycline (AC) and taxane (Tx) (regimen 1; n = 250); anthracycline, trastuzumab (Tmab), and taxane (regimen 2; n = 181); trastuzumab and taxane (regimen 3; n = 92); and taxane alone (regimen 4; n = 36). Site visits were scheduled before chemotherapy (baseline, Visit 0), and every 3 months after chemotherapy initiation [Visits 1 (90 ± 30 days) to 4 (360 ± 30 days)]. Visit 0, baseline; Visits 1–4, visits at 3, 6, 9, and 12 months after chemotherapy initiation, respectively. TTE = transthoracic echocardiogram.

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  Figure 2. Patient Flowchart Of 679 prospectively enrolled patients with breast cancer scheduled for neoadjuvant and/or adjuvant chemotherapy, 41 were excluded based on predefined criteria. Ultimately, 559 chemotherapy-naïve patients were included.

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  Figure 3. Risk Stratification Based on the CHECK HEART Score Participants (n = 559) in risk prediction model were divided into 3 risk-level groups based on their risk scores and cut-off values derived from classification and regression tree analysis. The incidence rates in the high-risk groups were notably higher than in the other groups.

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  Figure 4. The CHECK HEART Score: Time-Dependent Area Under the Curve The CHECK HEART score was derived using patient characteristics and clinical data at baseline (visit 0). The blue line and zone show the time-dependent area under the receiver operating characteristic curve (time-dependent AUC) and 95% CI. The time-dependent AUC at 12 months was 0.82 (95%CI 0.76-0.89).

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  Figure 5. Cumulative Incidence Curve of Cardiotoxicity Using the CHECK HEART Scores Cumulative incidence curves using the Fine-Gray model showing the incidence of cardiotoxicity in each risk group based on the CHECK HEART score. The solid lines show the incidence of cardiotoxicity and a competing risk (all-cause death), and the dashed lines show the incidence of a competing risk (all-cause death).

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  Central Illustration. Schematic Representation of the CHECK HEART-BC Study The CHECK HEART score was developed using baseline variables and demonstrated sufficient predictive accuracy at 12 months (time-dependent AUC: 0.82; 95% CI: 0.76-0.89). The formula for the CHECK HEART score was as follows: CHECK HEART score = (0.0269 × [heart rate at baseline, beats/min]) − (0.0384 × [LVDd at baseline, mm]) + (0.209 × [LVDs at baseline, mm]) + (0.199 × [LVGLS at baseline, %]) − (0.0540 × [RVFAC at baseline, %]) + (0.592 × treated with anthracycline and trastuzumab). Notably, approximately 70% of patients were assigned to the low-risk group in which the incidence of cardiotoxicity was only 2.9%. In clinical practice, the follow-up intervals may be extended for patients classified as low risk. Close surveillance is recommended for patients in the moderate- and high-risk groups to enable early detection and improve cardiovascular outcomes. AUC = area under the curve; LVDd = left ventricular diameters in diastole; LVDs = left ventricular diameters in systole; LVGLS = left ventricular global longitudinal strain; RVFAC = right ventricular fractional area change; Tmab = trastuzumab.