CPET provides physiologically valid, repeatable measures revealing impaired cardiac, ventilatory and muscular responses to peak effort exercise in DMD

Topic:

Other

Poster Number: T334

Author(s):

Tanja Taivassalo, PhD, University of Florida, Meghana Bomma, B.Sc, University of Florida, Sean Forbes, PhD, University of Florida, John-Anthony Coppola, MD, University of Florida, Carmen Leon, MD, U of Florida, Aditi Pant, MD, University of Florida, Julie Berthy, DNP, University of Florida, Benjamin McCaffrey, B.S, University of Florida, James May, B.S, University of Florida, Manuela Corti, PT, PhD, University of Florida, Renata Shih, MD, University of Florida, Donovan Lott, PT, PhD, University of Florida

BACKGROUND: Cardiopulmonary exercise testing (CPET) is the gold-standard for quantification of aerobic fitness (VO2peak, an objective, reliable and prognostic measure of health in clinical settings) but has not been readily applied to Duchenne muscular dystrophy (DMD). CPET is clinically useful as it provides simultaneous assessment of the adequacy of cardiac, ventilatory and muscular systems to deliver and utilize oxygen during progressive exercise to maximal exertion. Particularly as emerging disease-modifying treatments are expected to improve DMD pathophysiology, quantification of VO2peak and factors limiting exercise will become important in determining efficacy. OBJECTIVE: To establish utility of CPET in DMD by determining 1) whether measures are physiologically valid and DMD boys can reach established maximal effort criteria (defined as respiratory gas exchange (RER) ratio >1.03; peak heart rate (HR)>85% age-predicted (210-0.65xage); 2) test-retest repeatability of VO2peak and HR; and 3) which physiological system(s) limit VO2peak. METHODS: Participants underwent stationary cycling CPET from rest to peak-effort according to ACSM guidelines for clinical population with measurement of metabolic gas exchange, ventilation (VE) and HR. Limitations to peak-exercise were considered as cardiovascular (low O2-pulse, index of stroke volume), ventilatory (elevated VE/VO2) or peripheral (ventilatory threshold (VT) <40% theoretical VO2peak). RESULTS: 19 ambulatory boys with DMD (age 9.6+2.6 years) and 7 age-matched controls underwent CPET with no safety concerns. Maximal CPET criteria were met in 17/19 cases in DMD, with peak RER=1.10+0.08 and HR=173+14 bpm (86% age-predicted). Mean VO2peak (18.3+5.5 ml/kg/min) was 52% of controls. Test-retest repeatability was high (R2>0.92). DMD had low peak O2-pulse (3.4+1.0 versus 6.5+1.1 ml/beat, p<0.01), high peak VE/V02 (41.9+7.1 versus 34.3+4.7, p<0.01) and reached VT early (30.3+9.6% versus 62.7+15.3%, p<0.05) during exercise compared to controls. CONCLUSION: CPET provided physiologically valid and repeatable assessment of aerobic fitness and HR in >90% of DMD patients studied, demonstrating markedly low VO2peak attributable to peripheral limitation but also revealing abnormalities in cardiovascular and ventilatory systems during exercise. CPET warrants consideration as an objective, integrative approach to determine whether physiological responses normalize in response to emerging treatments in DMD.