Surveillance cardiopulmonary exercise testing can risk-stratify childhood cancer survivors: underlying pathophysiology of poor exercise performance and possible room for improvement

Background Asymptomatic childhood cancer survivors (CCS) frequently show decreased exercise performance. Poor exercise performance may indicate impaired future cardiovascular health. Methods Cardiopulmonary exercise testing (CPET) was performed in asymptomatic off-treatment CCS (age [greater than or equal to] 10 years). Patients were divided into Normal and Poor performance groups by %predicted maximum VO2 at 80%. Both peak and submaximal CPET values were analyzed. Results Thirty-eight males (19 Normal, 19 Poor) and 40 females (18 Normal, 22 Poor) were studied. Total anthracycline dosage was comparable among 4 groups. The body mass index (BMI), although normal, and weight were significantly higher in Poor groups. Peak heart rate (HR) and peak respiratory exchange ratio (RER) were comparable in all four groups. Peak work rate (pWR)/kg, peak oxygen consumption (pVO2)/kg, peak oxygen pulse (pOP)/kg, and ventilatory anaerobic threshold (VAT)/kg were significantly lower, whereas heart rate (HR) increase by WR/kg ([DELA]HR/[DELA][WR/kg] was significantly higher in Poor groups. Simultaneously plotting of weight & pVO2 and [DELA]HR/[DELA]WR & [DELA]VO2/[DELA]HR revealed a distinct difference between the Normal and Poor groups in both sexes, suggesting decreased skeletal muscle mass and decreased stroke volume reserve, respectively, in Poor CCS. The relationship between VAT and pVO2 was almost identical between the two groups in both sexes. Ventilatory efficiency was mildly diminished in the Poor groups. Conclusions Decreased skeletal muscle mass, decreased stroke volume reserve, and slightly decreased ventilatory efficiency characterize Poor CCS in both sexes. This unique combined CPET analysis provides useful clinical biomarkers to screen subclinical cardiovascular abnormality in CCS and identifies an area for improvement. Keywords: Cardiotoxicity, Chemotherapy, Anthracycline, Biomarker, Risk-stratification, Cardiovascular health