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

Late-onset cardiovascular complications are serious concerns for pediatric cancer survivors (PCS) including those who are asymptomatic. We investigated whether cardiopulmonary exercise testing (CPET) can delineate the underlying pathophysiology of preclinical cardiovascular abnormalities in PCS. We examined CPET data via cycle ergometer in asymptomatic PCS with normal echocardiogram and age-matched controls. Peak and submaximal parameters were analyzed. 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 W, 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 increment VE/ increment VCO2) were comparable. Peak respiratory exchange ratio (RER) was significantly higher in PCS (p = 0.0006). Stroke volume (SV) reserve was decreased in PCS, indicated by simultaneous higher dependency on HR (higher increment HR/ increment WR) and lower peak oxygen pulse (OP). Twelve PCS with high peak RER (>= 1.3) revealed lower pVO(2) and VAT than the rest of PCS despite higher ventilatory efficiency (lower increment VE/ increment VCO2), suggesting fundamental deficiency in oxygen utilization in some PCS. Poor exercise performance in PCS may be mainly attributed to limited stroke volume reserve, but the underlying pathophysiology is multifactorial. Combined assessment of peak and submaximal CPET parameters provided critical information in delineating underlying exercise physiology of PCS.