Decreased Native T1 Values and Impaired Myocardial Contractility in Anabolic Steroid Users.

Anabolic androgenic steroid (AAS) abuse leads to myocardial toxicity. Human studies are conflicting about the myocardial fibrosis in AAS users. We evaluated cardiac tissue characterization, left ventricle (LV) function, and cardiac structure by cardiovascular magnetic resonance (CMR). Twenty strength-trained AAS users (AASU) aged 29±5 yr, 20 strength-trained AAS nonusers (AASNU), and 7 sedentary controls (SC) were enrolled. Native T1 mapping, late-gadolinium enhancement (LGE), extracellular volume (ECV), and myocardial strain were evaluated. AASU showed lower Native T1 values than AASNU (888±162 vs. 1020±179 ms p=0.047). Focal myocardial fibrosis was found in 2 AASU. AASU showed lower LV radial strain (30±8 vs. 38±6%, p<0.01), LV circumferential strain (-17±3 vs. -20±2%, p<0.01), and LV global longitudinal strain (-17±3 vs. -20±3%, p<0.01) than AASNU by CMR. By echocardiography, AASU demonstrated lower 4-chamber longitudinal strain than AASNU (-15±g3 vs. -18±2%, p=0.03). ECV was similar among AASU, AASNU, and SC (28±10 vs. 28±7 vs. 30±7%, p=0.93). AASU had higher LV mass index than AASNU and SC (85±14 vs. 64±8 vs. 58±5 g/m2, respectively, p<0.01). AAS abuse may be linked to decreased myocardial native T1 values, impaired myocardial contractility, and focal fibrosis. These alterations may be associated with maladaptive cardiac hypertrophy in young AAS users.

Sacubitril/valsartan versus enalapril on exercise capacity in patients with heart failure with reduced ejection fraction: A randomized, double-blind, active-controlled study.

Sacubitril/valsartan reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) when compared with enalapril. However, it is unknown the effect of both treatments on exercise capacity. We compared sacubitril/valsartan versus enalapril in patients with HFrEF based on peak oxygen consumption (VO2) and 6-minute walk test (6-MWT). METHODS: We included 52 participants with HFrEF with a left ventricular ejection fraction <40% to receive either sacubitril/valsartan (target dose of 400 mg daily) or enalapril (target dose of 40 mg daily). Peak VO2 was measured by using cardiopulmonary exercise testing. Six-minute walk test was also performed. RESULTS: At 12 weeks, the sacubitril/valsartan (mean dose 382.6 ± 57.6 mg daily) group had increased peak VO2 of 13.1% (19.35 ± 0.99 to 21.89 ± 1.04 mL/kg/min) and enalapril (mean dose 34.4 ± 9.2 mg daily) 5.6% (18.58 ± 1.19 to 19.62 ± 1.25 mL/kg/min). However, no difference was found between groups (P = .332 interaction). At 24 weeks, peak VO2 increased 13.5% (19.35 ± 0.99 to 21.96 ± 0.98 mL/kg/min) and 12.0% (18.58 ± 1.19 to 20.82 ± 1.18 mL/kg/min) in sacubitril/valsartan (mean dose 400 ± 0 mg daily) and enalapril (mean dose 32.7 ± 11.0 mg daily), respectively. However, no differences were found between groups (P= .332 interaction). At 12 weeks, 6-MWT increased in both groups (sacubitril/valsartan: 459 ± 18 to 488 ± 17 meters [6.3%] and enalapril: 443 ± 22 to 477 ± 21 meters [7.7%]). At 24 weeks, sacubitril/valsartan increased 18.3% from baseline (543 ± 26 meters) and enalapril decreased slightly to 6.8% (473 ± 31 meters), but no differences existed between groups (P= .257 interaction). CONCLUSIONS: Compared to enalapril, sacubitril/valsartan did not substantially improve peak VO2 or 6-MWT after 12 or 24 weeks in participants with HFrEF. (NEPRIExTol-HF Trial, ClinicalTrials.gov number, NCT03190304).

Retrograde and oscillatory shear rate in young anabolic androgenic steroid users.

Disturbed shear rate (SR), characterized by increased retrograde and oscillatory SR in the brachial artery, is associated with inflammation, atherosclerosis, endothelial dysfunction, and sympathetic hyperactivity. Young subjects do not have disturbed SR; however, elderly subjects do, which seems to be associated with sympathetic hyperactivity. Anabolic androgenic steroids (AAS) abuse in young is associated with increased muscle sympathetic nerve activity (MSNA). We hypothesized that AAS users might have disturbed SR. We tested the association between retrograde and oscillatory SR with MSNA. In addition, we measured the high-sensitivity C-reactive protein (hs-CRP). We evaluated 10 male AAS users, age 27 ± 4 years, and 10 age-matched AAS nonusers, age 29 ± 5 years. At rest, retrograde and oscillatory SR were evaluated by Doppler ultrasound, MSNA was measured with microneurography, and hs-CRP was measured in blood sample. Flow-mediated dilation (FMD) was also assessed. AAS users had higher retrograde SR (24.42 ± 17.25 vs 9.15 ± 6.62 s- 1 , P = 0.01), oscillatory SR (0.22 ± 0.13 vs 0.09 ± 0.07 au P = 0.01), and MSNA (42 ± 9 vs 32 ± 4 bursts/100 heart beats, P = 0.018) than nonusers. MSNA (bursts/100 heart beats) was correlated with retrograde SR (r = 0.50, P = 0.050) and oscillatory SR (r = 0.51, P = 0.042). AAS users had higher hs-CRP [1.17 (0.44-3.63) vs 0.29 (0.17-0.70) mg/L, P = 0.015] and decreased FMD (6.42 ± 2.07 vs 8.28% ± 1.53%, P = 0.035) than nonusers. In conclusion, AAS abuse is associated with retrograde and oscillatory SR which were associated with augmented sympathetic outflow. In addition, AAS seems to lead to inflammation characterized by increased hs-CRP. These alterations may have the potential of increasing the early risk of atherosclerotic disease in young AAS users.

Association of Sarcopenia and Oxygen Uptake Efficiency Slope in Male Patients With Heart Failure.

PURPOSE: Sarcopenia, the loss of muscle mass and function, is a common comorbidity in patients with heart failure (HF). The skeletal muscle modulates the respiratory response during exercise. However, whether ventilatory behavior is affected by sarcopenia is still unknown. METHODS: We enrolled 169 male patients with HF. Muscle strength was measured by a handgrip dynamometer. Body composition was measured with dual-energy X-ray absorptiometry. Sarcopenia was defined by handgrip strength <27 kg and appendicular lean mass divided by height squared (ALM/height 2 ) <7.0 kg/m 2 . Oxygen uptake efficiency slope (OUES), ventilation (VE), oxygen uptake (VO 2 ), and carbon dioxide output (VCO 2 ) were measured by a cardiopulmonary exercise test. RESULTS: Sarcopenia was identified in 29 patients (17%). At the first ventilatory threshold, VE/VO 2 (36.9 ± 5.9 vs 32.7 ± 6.5; P = .003) and VE/VCO 2 (39.8 ± 7.2 vs 35.3 ± 6.9; P = .004) were higher in patients with sarcopenia compared to those without sarcopenia. At the exercise peak, compared to patients without sarcopenia, patients with sarcopenia had lower OUES (1186 ± 295 vs 1634 ± 564; P < .001), relative VO 2 (16.2 ± 5.0 vs 19.5 ± 6.5 mL/kg/min; P = .01), and VE (47.3 ± 10.1 vs 63.0 ± 18.2 L/min; P < .0001), while VE/VCO 2 (42.9 ± 8.9 vs 38.7 ± 8.4; P = .025) was increased. OUES was positively correlated with ALM/height 2 ( r = 0.36; P < .0001) and handgrip strength ( r = 0.31; P < .001). Hemoglobin (OR = 1.149; 95% CI, 0.842-1.570; P = .038), ALM/height 2 (OR = 2.166; 95% CI, 1.338-3.504; P = .002), and VO 2peak (OR = 1.377; 95% CI, 1.218-1.557; P < .001) were independently associated with OUES adjusted by cofounders. CONCLUSIONS: Our results suggest that sarcopenia is related to impaired ventilatory response during exercise in patients with HF.

Association of physical activity levels and the prevalence of COVID-19-associated hospitalization.

OBJECTIVES: We compared physical activity levels before the outbreak and quarantine measures with COVID-19-associated hospitalization prevalence in surviving patients infected with SARS-CoV-2. Additionally, we investigated the association of physical activity levels with symptoms of the disease, length of hospital stay, and mechanical ventilation. DESIGN: Observational, cross-sectional. METHODS: Between June 2020 and August 2020, we invited Brazilian survivors and fully recovered patients infected with SARS-CoV-2 to respond to an online questionnaire. We shared the electronic link to the questionnaire on the internet. We collected data about clinical outcomes (symptoms, medications, hospitalization, and length of hospital stay) and cofactors, such as age, sex, ethnicity, preexisting diseases, socioeconomic and educational, and physical activity levels using the International Physical Activity Questionnaire (IPAQ short version). RESULTS: Out of 938 patients, 91 (9.7%) were hospitalized due to COVID-19. In a univariate analysis, sex, age, and BMI were all associated with hospitalizations due to COVID-19. Men had a higher prevalence of hospitalization (66.6%, p = 0.013). Patients older than 65 years, obese, and with preexisting disease had a higher prevalence of COVID-19-related hospitalizations. In a multivariate regression model, performance of at least 150 min/wk (moderate) and/or 75 min/wk (vigorous) physical activity was associated with a lower prevalence of hospitalizations after adjustment for age, sex, BMI, and preexisting diseases (PR = 0.657; p = 0.046). CONCLUSIONS: Sufficient physical activity levels were associated with a lower prevalence of COVID-19-related hospitalizations. Performing at least 150 min a week of moderate-intensity, or 75 min a week of vigorous-intensity physical activity was associated with 34.3% reduction in prevalence.

Aerobic exercise and inspiratory muscle training increase functional capacity in patients with univentricular physiology after Fontan operation: A randomized controlled trial.

BACKGROUND: The effect of exercise training and its mechanisms on the functional capacity improvement in Fontan patients (FP) are virtually unknown. This trial evaluated four-month aerobic exercise training and inspiratory muscle training on functional capacity, pulmonary function, and autonomic control in patients after Fontan operation. METHODS: A randomized controlled clinical trial with 42 FP aged 12 to 30 years and, at least, five years of Fontan completion. Twenty-seven were referred to a four-months supervised and personalized aerobic exercise training (AET) or an inspiratory muscle training (IMT). A group of non-exercise (NET) was used as control. The effects of the exercise training in peak VO2; pulmonary volumes and capacities, maximal inspiratory pressure (MIP); muscle sympathetic nerve activity (MSNA); forearm blood flow (FBF); handgrip strength and cross-sectional area of the thigh were analyzed. RESULTS: The AET decreased MSNA (p = 0.042), increased FBF (p = 0.012) and handgrip strength (p = 0.017). No significant changes in autonomic control were found in IMT and NET groups. Both AET and IMT increased peak VO2, but the increase was higher in the AET group compared to IMT (23% vs. 9%). No difference was found in the NET group. IMT group showed a 58% increase in MIP (p = 0.008) in forced vital capacity (p = 0.011) and forced expiratory volume in the first second (p = 0.011). No difference in pulmonary function was found in the AET group. CONCLUSIONS: Both aerobic exercise and inspiratory muscle training improved functional capacity. The AET group developed autonomic control, and handgrip strength, and the IMT increased inspiratory muscle strength and spirometry. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02283255.

Discriminating sarcopenia in overweight/obese male patients with heart failure: the influence of body mass index.

AIMS: The definition of sarcopenia based on appendicular lean mass/height (2) (ALM/height (2) ) is often used, although it can underestimate the prevalence of sarcopenia in overweight/obese patients with heart failure. Therefore, new methods have been proposed to overcome this limitation. We aimed to evaluate the prevalence of sarcopenia by three methods and compare body composition in this population. METHODS AND RESULTS: We enrolled 168 male patients with heart failure (left ventricular ejection fraction <40%). Sixty-six patients (39.3%) were identified with sarcopenia by at least one method. The lower 20th percentile defined as the cut-off point for sarcopenia was 7.03 kg/m2 , -2.32 and 0.76 for Baumgartner's (20.8%), Newman's (21.4%), and Studenski's methods (21.4%), respectively. Patients with body mass index (BMI) <25 kg/m2 were more likely to be identified by Baumgartner's than Studenski's method (P < 0.001). However, in patients with BMI ≥ 25 kg/m2 , Studenski's and Newman's methods were more likely to detect sarcopenia than Baumgartner's method (both P < 0.005). Patients were further divided into three subgroups: (i) patients classified in all indexes (n = 8), (ii) patients classified in Baumgartner's (sarcopenic; n = 27), and (iii) patients classified in both Newman's and Studenski's methods (sarcopenic obesity; n = 31). Comparing body composition among groups, all sarcopenic groups presented lower total lean mass compared with non-sarcopenic patients, whereas sarcopenic obese patients had higher total lean mass than lean sarcopenic patients. CONCLUSIONS: Our results demonstrate that the prevalence of sarcopenia in overweight/obese patients is similar to lean sarcopenic patients when other methods are considered. In patients with higher BMI, Studenski's method seems to be more feasible to detect sarcopenia.

Muscle mass, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies.

AIMS: Patients with Chagas disease and heart failure (HF) have a poor prognosis similar to that of patients with ischaemic or dilated cardiomyopathy. However, the impact of body composition and muscle strength changes in these aetiologies is still unknown. We aimed to evaluate these parameters across aetiologies in two distinct cohort studies [TESTOsterone-Heart Failure trial (TESTO-HF; Brazil) and Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF; Germany)]. METHODS AND RESULTS: A total of 64 male patients with left ventricular ejection fraction ≤40% were matched for body mass index and New York Heart Association class, including 22 patients with Chagas disease (TESTO-HF; Brazil), and 20 patients with dilated cardiomyopathy and 22 patients with ischaemic heart disease (SICA-HF; Germany). Lean body mass (LBM), appendicular lean mass (ALM), and fat mass were assessed by dual energy X-ray absorptiometry. Sarcopenia was defined as ALM divided by height in metres squared <7.0 kg/m2 (ALM/height2 ) and handgrip strength cut-off for men according to the European Working Group on Sarcopenia in Older People. All patients performed maximal cardiopulmonary exercise testing. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Chagasic and ischaemic patients had lower total fat mass (16.3 ± 8.1 vs. 19.3 ± 8.0 vs. 27.6 ± 9.4 kg; P < 0.05) and reduced peak oxygen consumption (VO2 ) (1.17 ± 0.36 vs. 1.15 ± 0.36 vs. 1.50 ± 0.45 L/min; P < 0.05) than patients with dilated cardiomyopathy, respectively. Chagasic patients showed a trend towards decreased LBM when compared with ischaemic patients (48.3 ± 7.6 vs. 54.2 ± 6.3 kg; P = 0.09). Chagasic patients showed lower handgrip strength (27 ± 8 vs. 37 ± 11 vs. 36 ± 14 kg; P < 0.05) and FBF (1.84 ± 0.54 vs. 2.75 ± 0.76 vs. 3.42 ± 1.21 mL/min/100 mL; P < 0.01) than ischaemic and dilated cardiomyopathy patients, respectively. There was no statistical difference in the distribution of sarcopenia between groups (P = 0.87). In addition, FBF correlated positively with LBM (r = 0.31; P = 0.012), ALM (r = 0.25; P = 0.046), and handgrip strength (r = 0.36; P = 0.004). In a logistic regression model using peak VO2 as the dependent variable, haemoglobin (odds ratio, 1.506; 95% confidence interval, 1.043-2.177; P = 0.029) and ALM (odds ratio, 1.179; 95% confidence interval, 1.011-1.374; P = 0.035) were independent predictors for peak VO2 adjusted by age, left ventricular ejection fraction, New York Heart Association, creatinine, and FBF. CONCLUSIONS: Patients with Chagas disease and HF have decreased fat mass and exhibit reduced peripheral blood flow and impaired muscle strength compared with ischaemic HF patients. In addition, patients with Chagas disease and HF show a tendency to have greater reduction in total LBM, with ALM remaining an independent predictor of reduced functional capacity in these patients. The percentage of patients affected by sarcopenia was equal between groups.

Android to gynoid fat ratio and its association with functional capacity in male patients with heart failure.

AIMS: We studied the association between android (A) to gynoid (G) fat ratio and functional capacity (peak VO2 ) in male patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We enrolled 118 male patients with HFrEF with left ventricular ejection fraction (LVEF) <40%. Body composition (by using dual x-ray absorptiometry) and peak VO2 (by cardiopulmonary exercise testing) were measured. Sarcopenic obesity was defined according to the Foundation for the National Institutes of Health criteria (FNIH). Blood sample for metabolic and hormonal parameters were measured. Fifteen patients (12.7%) showed sarcopenic obesity (body mass index > 25 kg/m2 with FNIH index < 0.789). The median A/G ratio was 0.55. A/G ratio > 0.55 was detected in 60 patients. Relative peak VO2 was lower in patients with A/G ratio > 0.55 than in patients with A/G ratio <0.55 (18.7 ± 5.3 vs. 22.5 ± 6.1 mL/kg/min, P < 0.001). Logistic regression analysis showed A/G ratio >0.55 to be independently associated with reduced peak VO2 adjusted for age, body mass index, LVEF, presence of sarcopenia, anabolic hormones, and haemoglobin (odds ratio 3.895, 95% confidence interval 1.030-14.730, P = 0.045). CONCLUSIONS: Body fat distribution, particularly android and gynoid fat composition, together with other cofactors, might have an important adverse role on functional capacity in male patients with HFrEF. Future studies are needed to address possible mechanisms involved in this relationship.

Neurovascular Response during Exercise and Mental Stress in Anabolic Steroid Users.

PURPOSE: Increased resting muscle sympathetic nerve activity (MSNA) and lower forearm blood flow (FBF) were observed in young men who use anabolic androgenic steroids (AAS). However, the response of MSNA and FBF in AAS users triggered by muscle mechanoreflex and central command has never been tested. In addition, we evaluated the blood pressure (BP) and heart rate (HR) responses during these maneuvers. METHODS: Nineteen AAS users (AASU) 31 ± 6 yr of age and 18 AAS nonusers (AASNU) 29 ± 4 yr of age were recruited. All participants were involved in strength training. AAS use was determined using a urine test (liquid chromatography with tandem mass spectrometry). MSNA was measured using the microneurography technique. FBF was measured by using venous occlusion plethysmography. BP was measured using an automatic oscillometric device. HR was recorded continuously through ECG. Isometric handgrip exercise was performed at 30% of the maximal voluntary contraction for 3 min, and mental stress was elicited by the Stroop color-word test for 4 min. RESULTS: The MSNA and FBF responses during exercise were similar between AASU and AASNU, with a trend toward higher MSNA (bursts per minute; P = 0.084) and lower forearm vascular conductance (FVC; units; P = 0.084) in AASU than in AASNU. During mental stress, AASU showed a significantly higher MSNA (P < 0.05) and lower FBF (P < 0.05) compared with AASNU. During both maneuvers, HR and BP increased linearly in both groups; however, AASU showed a significantly higher HR compared with AASNU. CONCLUSIONS: During muscle mechanoreflex activation (isometric exercise), AASU have normal MSNA and FBF responses, whereas during central command (mental stress) stimulation, AASU have exacerbated MSNA and blunted vasodilation. Therefore, mental stress seems to exacerbate neurovascular control throughout stress reaction situations in AASU.

Blunted peripheral blood supply and underdeveloped skeletal muscle in Fontan patients: The impact on functional capacity.

BACKGROUND: Changes in circulatory physiology are common in Fontan patients due to suboptimal cardiac output, which may reduce the peripheral blood flow and impair the skeletal muscle. The objective of this study was to investigate the forearm blood flow (FBF), cross-sectional area (CSA) of the thigh and functional capacity in asymptomatic clinically stable patients undergoing Fontan surgery. METHODS: Thirty Fontan patients and 27 healthy subjects underwent venous occlusion plethysmography, magnetic resonance imaging of the thigh musculature and maximal cardiopulmonary exercise testing. Muscle sympathetic nerve activity (MSNA), norepinephrine measures, cardiovascular magnetic resonance, handgrip strength and 6-minute walk test were also performed. RESULTS: Fontan patients have blunted FBF (1.59 ±â€¯0.33 vs 2.17 ±â€¯0.52 mL/min/100 mL p < 0.001) and forearm vascular conductance (FVC) (1.69 ±â€¯0.04 vs 2.34 ±â€¯0.62 units p < 0.001), reduced CSA of the thigh (81.2 ±â€¯18.6 vs 116.3 ±â€¯26.4 cm2p < 0.001), lower peak VO2 (29.3 ±â€¯6 vs 41.5 ±â€¯9 mL/kg/min p < 0.001), walked distance (607 ±â€¯60 vs 701 ±â€¯58 m p < 0.001) and handgrip strength (21 ±â€¯9 vs 30 ±â€¯8 kgf p < 0.001). The MSNA (30 ±â€¯4 vs 22 ±â€¯3 bursts/min p < 0.001) and norepinephrine concentration [265 (236-344) vs 222 (147-262) pg/mL p = 0.006] were also higher in Fontan patients. Multivariate linear regression showed FVC (ß = 0.653; CI = 0.102-1.205; p = 0.022) and stroke volume (ß = 0.018; CI = 0.007-0.029; p = 0.002) to be independently associated with reduced CSA of the thigh adjusted for body mass index. The CSA of the thigh adjusted for body mass index (ß = 5.283; CI = 2.254-8.312; p = 0.001) was independently associated with reduced peak VO2. CONCLUSION: Patients with Fontan operation have underdeveloped skeletal muscle with reduced strength that is associated with suboptimal peripheral blood supply and diminished exercise capacity.