170PHeart rate and ventilation during submaximal cycling exercise as physiological outcome measures in Duchenne muscular dystrophy

Timed function tests and the 6-minute-walk distance are standard efficacy outcomes in clinical trials of boys with Duchenne muscular dystrophy (DMD). However, they are subject to motivation and ambulatory ability and provide limited information on cardiorespiratory function during physical activity. Given that the heart and respiratory muscles are involved in DMD pathology, along with the potential of emerging therapeutics to improve physical function, an assessment approach to quantify cardiorespiratory parameters in ambulatory and non-ambulatory boys is needed. We recently performed maximal effort cardiopulmonary exercise testing to measure peak heart rate (HR) and ventilation (VE), reporting it valid in 81.5% of DMD boys tested (Bomma et al, 2025). Measurement of these outcomes during submaximal exercise is commonly used to reflect physiological efficiency in other clinical populations, but has never been reported in DMD. Our current aim is to examine heart rate (HR) and ventilation (VE) relative to oxygen uptake (VO₂) during submaximal cycling and highlight their potential as physiological measures in ambulatory (A) and non-ambulatory (NA) boys with DMD. Eleven A-DMD (10±3.5 years), 3 NA-DMD (15.6±4.1 yrs) and 7 healthy controls (11±2 years) performed submaximal exercise (unloaded warm-up followed by 5 watt increments in 2-minute stages up to 15 watts) on a leg or arm ergometer (Lode Corival or Angio, the Netherlands). HR, VE and VO₂ were measured at every stage (Cosmed Quark metabolic cart), and the oxygen uptake efficiency slope (OUES) was calculated from the slope of increase in VO₂ and log VE. OUES relative to body surface area (BSA) is an objective reproducible measure of the integrated efficiency of the body to utilize oxygen for energy production during activity and is not influenced by exercise intensity (Akkerman M, et al, 2010). All A-DMD completed at least 15 watts and NA-DMD completed at least 5 watts of submaximal cycling with no adverse events. Comparison at 5 watts revealed higher exercise HR in A-DMD (133±11.6 bpm) and NA-DMD (140±24.3 bpm) compared to controls (95.2±16.8 bpm, p<0.001). Similarly at higher workloads, HR was higher in DMD compared to controls at 10 watts (133.3±14.4 versus 96.5±17.4 bpm, p<0.01) and 15 watts (145.4±16.9 versus 101.3±18.3 bpm, p<0.01). The OUES/BSA was lower in A-DMD and NA-DMD compared to controls (1530.0±195; 963.1±178; 645.1±285.0 ml/L/m² respectively p<0.0001), reflecting a hyperventilatory response to oxygen uptake and inefficiency of aerobic metabolism. Our findings reveal that boys with DMD demonstrate high HR and ventilatory responses during submaximal exercise, which reflect inefficient physiological responses to the increasing demands of exercise. Our data support the use of submaximal HR and OUES/BSA to elucidate cardiorespiratory limitations relating to disease severity and determine whether therapeutics improve these inefficiencies in A and NA-DMD.