Exercise Intolerance in Facioscapulohumeral Muscular Dystrophy

Abstract

Purpose: Determine 1) if adults with facioscapulohumeral muscular dystrophy (FSHD) exhibit exercise intolerance and 2) potential contributing mechanisms to exercise intolerance, specific to FSHD.

Methods: Eleven people with FSHD (47 ± 13 yr, 4 females) and 11 controls (46 ± 13 yr, 4 females) completed one visit, which included a volitional peak oxygen consumption (V̇O2peak) cycling test. Breath-by-breath gas exchange, ventilation, and cardiovascular responses were measured at rest and during exercise. The test featured 3-min stages (speed, 65-70 rpm) with incremental increases in intensity (FSHD: 20 W per stage; control: 40-60 W per stage). Body lean mass (LM (kg, %)) was collected via dual-energy x-ray absorptiometry.

Results: V̇O2peak was 32% lower (24.5 ± 9.7 vs 36.2 ± 9.3 mL·kg-1·min-1, P < 0.01), and wattage was 55% lower in FSHD (112.7 ± 56.1 vs 252.7 ± 67.7 W, P < 0.01). When working at a relative submaximal intensity (40% of V̇O2peak), wattage was 55% lower in FSHD (41.8 ± 30.3 vs 92.7 ± 32.6 W, P = 0.01), although ratings of perceived exertion (FSHD: 11 ± 2 vs control: 10 ± 3, P = 0.61) and dyspnea (FSHD: 3 ± 1 vs control: 3 ± 2, P = 0.78) were similar between groups. At an absolute intensity (60 W), the rating of perceived exertion was 63% higher (13 ± 3 vs 8 ± 2, P < 0.01) and dyspnea was 180% higher in FSHD (4 ± 2 vs 2 ± 2, P < 0.01). V̇O2peak was most strongly correlated with resting O2 pulse in controls (P < 0.01, r = 0.90) and percent leg LM in FSHD (P < 0.01, r = 0.88). Among FSHD participants, V̇O2peak was associated with self-reported functionality (FSHD-HI score; activity limitation: P < 0.01, r = -0.78), indicating a strong association between perceived and objective impairments.

Conclusions: Disease-driven losses of LM contribute to exercise intolerance in FSHD, as evidenced by a lower V̇O2peak and elevated symptoms of dyspnea and fatigue during submaximal exercise. Regular exercise participation may preserve LM, thus providing some protection against exercise tolerance in FSHD.

Figure 1:

Peak exercise capacity in FSHD. 1A) VO_2peak was lower than that observed in controls; 1B) Peak wattage was lower among people with FSHD (VO₂, volume of oxygen consumption; *p<0.01 for both).

Figure 2:

Self-reported exertion levels in FSHD. 2A) During relative work, ratings of perceived exertion did not differ between people with FSHD and controls; 2B) The FSHD group had self-reported levels of breathlessness that were similar to controls, when working at a relative intensity (RPE, rating of perceived exertion; 40%, submaximal exercise at 40% of VO_2peak; Peak, VO_2peak; p>0.05 for both).

Figure 3:

Measures of ventilation during exercise in FSHD. 3A) V_E response during maximal exercise was significantly lower in FSHD; 3B) People with FSHD demonstrated a R_R that was significantly higher than controls while at rest, but increased similarly throughout exercise; 3C) Overall, V_T is lower among people with FSHD, as compared with controls) (V_E, minute ventilation; R_R, respiratory rate; V_T, tidal volume; 40%, submaximal exercise at 40% of VO_2peak; Peak, VO_2peak; *p<0.05).