Traditional markers of cardiac toxicity fail to detect marked reductions in cardiorespiratory fitness among cancer patients undergoing anti-cancer treatment

Left ventricular ejection fraction (LVEF) is standard of care for evaluating chemotherapy-associated cardiotoxicity, although global longitudinal strain (GLS) offers advantages. However, neither change in LVEF or GLS has been associated with short-term symptoms, functional capacity, or long-term heart failure (HF) risk. We sought to determine whether an integrative measure of cardiovascular function (VO₂peak) that is strongly associated with HF risk would be more sensitive to cardiac damage induced by cancer treatment than LVEF, GLS, or cardiac biomarkers.

Patients (n = 206, 53 ± 13 years, 35% male) scheduled to commence anti-cancer treatment completed assessment prior to, and within 6 months after therapy. Changes in echocardiographic measures of LV function (LVEF, GLS), cardiac biomarkers (troponin and BNP), and cardiorespiratory fitness (VO₂peak) were measured. LV function was normal prior to treatment (LVEF 61 ± 5%; GLS −19.4 ± 2.1), but VO₂peak was only 88 ± 26% of age-predicted. After treatment, VO₂peak was reduced by 7 ± 15% (equivalent of 7 years normal ageing, P < 0.0001) and the rates of functional disability (defined as VO₂peak ≤ 18 mL/min/kg) almost doubled (15% vs. 26%, P = 0.016). In contrast, small, reductions in LVEF (59 ± 5% vs. 58 ± 5%, P = 0.03) and GLS (−19.4 ± 2.1 vs. −18.9 ± 2.2, P = 0.002) and an increase in troponin levels (4.0 ± 6.9 vs. 26.4 ± 26.2 ng/mL, P < 0.0001) were observed.

Anti-cancer treatment is associated with marked reductions in functional capacity that occur independent of reductions in LVEF and GLS. The assessment of VO₂peak prior to, and following treatment may be a more sensitive means of identifying patients at increased risk of HF.