Cardiopulmonary Exercise Testing Characterizes Silent Cardiovascular Abnormalities in Asymptomatic Pediatric Cancer Survivors

Background: Late-onset cardiovascular complications are of serious concerns for even asymptomatic pediatric cancer survivors (PCS). We investigated whether cardiopulmonary exercise testing (CPET) can delineate the underlying pathophysiology of preclinical cardiovascular abnormalities in PCS. Methods We examined CPET data via cycle ergometer in asymptomatic PCS with normal echocardiogram and age-matched controls. Peak and submaximal parameters were analyzed. Results Fifty-three PCS and 60 controls were studied. Peak oxygen consumption (VO2), peak work rate (WR), and ventilatory anaerobic threshold (VAT) were significantly lower in PCS than controls (1.86 ± 0.53 vs. 2.23 ± 0.61 L/min, 125 ± 45 vs. 154 ± 46 watt, and 1.20 ± 0.35 vs. 1.42 ± 0.43 L/min, respectively; all p  < 0.01), whereas peak heart rate (HR) and ventilatory efficiency (a slope of minute ventilation over CO2 production or DVE/DVCO2) were comparable. Peak respiratory quotient (RQ) was significantly higher in PCS ( p  = 0.0006). Stroke volume (SV) reserve was decreased in PCS, indicated by simultaneous higher dependency on HR (higher ΔHR/ΔWR) and lower peak oxygen pulse (OP) at the peak exercise. Twelve PCS with high peak RQ (≥ 1.3) revealed lower pVO2 and VAT than the rest of PCS despite higher ventilatory efficiency (lower DVE/DVCO2), suggesting fundamental deficiency in oxygen utilization in some PCS. Conclusions Poor exercise performance in PCS is mainly attributed to limited stroke volume reserve, but the underlying pathophysiology is multi-factorial. Combined assessment of peak and submaximal CPET parameters provided critical information in delineating underlying exercise physiology of PCS. (244 words)