Corrigendum: Sarcopenic Obesity in Facioscapulohumeral Muscular Dystrophy.

[This corrects the article DOI: 10.3389/fphys.2020.01008.].

Baroreflex sensitivity in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD), a common form of muscular dystrophy, is caused by a genetic mutation that alters DUX4 gene expression. This mutation contributes to significant skeletal muscle loss. Although it is suggested that cardiac muscle may be spared, people with FSHD have demonstrated autonomic dysregulation. It is unknown if baroreflex function, an important regulator of blood pressure (BP), is impaired in people with FSHD. We examined if baroreflex sensitivity (BRS) is blunted in patients with FSHD. Thirty minutes of resting BP, heart rate, and cardiovagal BRS were measured in 13 patients with FSHD (age: 50 ± 13 years, avg ± SD) and 17 sex- and age-matched controls (age: 47 ± 14 years, p > 0.05). People with FSHD were less active (Activity Metabolic Index, AMI) (FSHD: 24 ± 30; controls: 222 ± 175 kcal/day; p < 0.001) but had a similar body mass index compared with controls (FSHD: 27 ± 4; controls: 27 ± 4 kg/m2 ; p > 0.05). BRSup (hypertensive response), BRSdown (hypotensive response), and total BRS were similar between groups (BRSup: FSHD: 12 ± 8; controls: 12 ± 5 ms/mmHg; BRSdown: FSHD: 10 ± 4; controls: 13 ± 6 ms/mmHg; BRS: FSHD: 14 ± 9; controls: 13 ± 6 ms/mmHg; p > 0.05). Mean arterial pressure was similar between groups (FSHD: 96 ± 7; controls: 91 ± 6mmHg). Individuals with FSHD had an elevated heart rate compared with controls (FSHD: 65 ± 8; controls: 59 ± 8 BPM; p = 0.03), but when co-varied for AMI, this relationship disappeared (p = 0.39). These findings suggest that BRS is not attenuated in people with FSHD, but an elevated heart rate may be due to low physical activity levels, a potential consequence of limited mobility.

Exercise Intolerance in Facioscapulohumeral Muscular Dystrophy.

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.

Menstrual phase does not influence ventilatory responses to group III/IV afferent signaling in eumenorrheic young females.

Estrogen can reduce sympathetic activity, but its effects on minute ventilation (VE) with group III/IV afferent activation remain unclear. This study examined the influence of estrogen on VE during lower-extremity exercise with group III/IV activation. Females completed two identical visits in follicular and ovulatory menstrual phases. Nine participants (age 25 ± 4 years) performed three minutes of baseline steady-state cycle ergometry and then group III/IV afferents were further activated with proximal thigh cuffs inflated to 20, 60, and 100 mmHg (randomized) for two minutes and five minutes of cycling between each occlusion. Metaboreflex was isolated by post-exercise circulatory occlusion. Ventilation was measured continuously and rating of perceived exertion (RPE) was recorded for each stage. During rest and exercise, VE (p < 0.001) and tidal volume (VT) (p = 0.033) were higher in the follicular than ovulatory phase. Minute ventilation, VT, and respiratory rate (RR) with ergoreflex and metaboreflex activation were similar across phases. With cuff occlusion of 100 mmHg, VE increased from baseline by 26.3 ± 7.0 L/min in the follicular phase (p < 0.001) and by 25.3±7.7 L/min in the ovulatory phase (p < 0.001), with no difference between phases (p> 0.05); RR and VT increased similarly with occlusion, also with no phase differences. In eumenorrheic females, menstrual phase influences ventilation but not ventilatory responses to group III/IV isolation.

Resting metabolic rate in adults with facioscapulohumeral muscular dystrophy.

This study aimed to determine whether resting metabolic rate (RMR) is altered in adults with facioscapulohumeral muscular dystrophy (FSHD). Eleven people with FSHD (51 ± 12yrs, 2 females) and 11 controls (48 ± 14 yrs, 2 females) completed 1 visit, including 30-minutes of indirect calorimetry and dual-energy X-ray absorptiometry (DXA) scanning. RMR was calculated from resting oxygen consumption/carbon dioxide production; regional/whole-body fat mass and lean mass were collected from the DXA scan. Absolute RMR was 15% lower in FSHD (p = 0.04); when normalized to regional/local lean mass, no differences in RMR were observed (p > 0.05). Absolute RMR was correlated with total lean mass for all participants combined (p < 0.01, r = 0.70, males only: p < 0.01, r = 0.81) and when analyzed separately (FSHD males: p = 0.001, r = 0.92 and control males: p = 0.004, r = 0.85). Whole-body lean mass was 16% lower in FSHD and leg, arm and appendicular lean mass were lower in FSHD (p < 0.05 for all), though trunk lean mass was not (p = 0.15). Whole-body fat mass was 45% higher in FSHD, with greater leg fat mass (p = 0.01), but not trunk or arm fat mass (p > 0.05 for both). When RMR was expressed relative to lean body mass, no differences in RMR were found, indicating that the lower levels of lean mass observed in FSHD patients likely contribute to the lower absolute RMR values. Novelty: RMR is lower among people with FSHD, as compared with controls. The reduced RMR among people with FSHD is due to disease-related loss in muscle mass and likely related to lower physical activity and/or exercise levels.

Sarcopenic Obesity in Facioscapulohumeral Muscular Dystrophy.

BACKGROUND: Sarcopenic obesity has been observed in people with neuromuscular impairment, and is linked to adverse health outcomes. It is unclear, however, if sarcopenic obesity develops in adults with facioscapulohumeral muscular dystrophy (FSHD). METHODS: The purpose of this study was to determine if adults with FSHD meet criteria for sarcopenic obesity (appendicular lean mass index (ALMI) scores of < 7.26 or 5.45 kg/m2; % fat mass (FM) ≥ 28 or 40% in men/women). Ten people with FSHD (50 ± 11 years, 2 females) and ten age/sex-matched controls (47 ± 13 years, 2 females) completed one visit, which included a full-body dual-energy x-ray absorptiometry (DXA) scan. Regional and whole body total mass, fat mass (FM), and lean mass (LM) were collected and body mass index (BMI) and sarcopenia measures were computed. RESULTS: People with FSHD and controls had a similar whole body total mass (84.5 ± 12.9 vs. 81.8 ± 13.5 kg, respectively, p = 0.65). Though BMI was 2% lower in the FSHD group (p = 0.77), the % FM was 46% higher in FSHD, compared with controls (p < 0.01). In addition, ALM volume was 23% lower (p = 0.02) and ALMI was 27% lower in FSHD compared with controls (p < 0.01). Whole body LM trended to be lower in FSHD vs. controls (p = 0.05), and arm and leg LM were both lower in FSHD compared with controls (p < 0.05). Furthermore, the % LM was 18% lower in FSHD vs. controls (p < 0.01). FSHD participants exhibited greater total body FM (p < 0.01) and total leg FM (p < 0.01), but were similar in volume of total arm FM compared with controls (p = 0.09). CONCLUSION: Findings from this study suggest that people with FSHD, although similar in BMI and total body mass compared with controls, commonly meet the definition of sarcopenic obesity. Adults with co-existing FSHD and sarcopenic obesity may be at risk for significant impairments in quality of life, and encounter additional challenges in the management of FSHD manifestations.