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Background: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells., Methods: This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis., Results: We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; p = .007), sit-to-stand (+256%; p = .01) and six-minute walking (+323%; p = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (-54.2%; p < .0001) and cell proliferation (-44.9%; p = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance., Conclusion: These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: The impact of COVID-19 goes beyond its acute form and can lead to the persistence of symptoms and the emergence of systemic disorders, defined as long-term COVID., Methods: We performed a cross-sectional study that included patients over 18 years of age who recovered from the severe form of COVID-19 at least 60 days after their discharge. Patients and controls were enrolled to undergo transthoracic echocardiography (TTE) using a more sensitive tool, myocardial work, in combination with cardiopulmonary exercise testing (CPET)., Results: A total of 52 patients and 31 controls were enrolled. Significant differences were observed in ejection fraction (LVEF; 62 ± 7 vs. 66 ± 6 %; p = 0.007), global longitudinal strain (LVGLS; -18.7 ± 2.6 vs. -20.4 ± 1.4 %; p = 0.001), myocardial wasted work (GWW; 152 ± 81 vs. 101 ± 54 mmHg; p = 0.003), and myocardial work efficiency (GWE; 93 ± 3 vs. 95 ± 2 %; p = 0.002). We found a significant difference in peak VO 2 (24.4 ± 5.4 vs. 33.4 ± 8.8 mL/kg/min; p < 0.001), heart rate (160 ± 14 vs. 176 ± 11 bpm; p < 0.001), ventilation (84.6 ± 22.6 vs. 104.9 ± 27.0 L/min; p < 0.001), OUES% (89 ± 16 vs. 102 ± 22 %; p = 0.002), T ½ (120.3 ± 32 vs. 97.6 ± 27 s; p = 0.002) and HRR at 2 min (-36 ± 11 vs. -43 ± 13 bpm; p = 0.010)., Conclusion: Our findings revealed an increased wasted work, with lower myocardial efficiency, significantly reduced aerobic exercise capacity, and abnormal heart rate response during recovery, which may be related to previously described late symptoms. The reduction in functional capacity during physical exercise is partly associated with a decrease in resting myocardial work efficiency. These findings strongly indicate the need to determine whether these manifestations persist in the long term and their impact on cardiovascular health and quality of life in COVID-19 survivors., (© 2024 The Authors.)

Background and Aims: Cardiovascular disease remains a leading cause of mortality, with statins widely used to reduce its risk. Despite extensive research, the nuanced impact of statin therapy on cardiorespiratory fitness, particularly the reduction in peak oxygen consumption (VO 2 ), is still an open question. This study aims to contribute fresh insights to the ongoing discussion, highlighting the unresolved nature of this clinical matter., Methods: We retrospectively analyzed maximal cardiopulmonary exercise test (CPET) in male and female participants over 18 years of age who were under statins treatment. They were categorized as physically active or inactive according to self-report of physical activity. From 33,804 CPET, 4,941 participants (76 % men, age 42 ± 13 years; and 24 % women, age 41 ± 13 years) were included in the study., Results: The multivariate linear regression model showed that statins were associated with a significant reduction in VO 2 peak (-4.2 [-4.8, -3.5] mL/kg/min, p < 0.01) after adjusting for age, sex, use of beta-blockers, antiarrhythmics, presence of diabetes, and weekly level of physical activity. This reduction in VO 2 peak was attenuated in participants with higher weekly physical activity volume (150 to 300 min/week: 3.2 [2.7; 3.7] mL/kg/min; 301 to 600 min/week: 4.5 [3.7; 5.3] mL/kg/min; and > 600 min/week: 6.9 [5.4; 8.4] mL/kg/min, all p < 0.01)., Conclusions: Statin use is associated with a lower VO 2 peak in adults. However, this adverse effect appears to be mitigated by engaging in regular physical activity (>150 min/week). Future research should explore the mechanisms behind this interaction and identify optimal exercise regimens for individuals on statin therapy., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Carlos Eduardo Negrao reports financial support and administrative support were provided by University of Sao Paulo Heart Institute. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (© 2024 Published by Elsevier B.V.)

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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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 (VO 2 ) 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 VO 2 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 VO 2 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 VO 2 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 VO 2 or 6-MWT after 12 or 24 weeks in participants with HFrEF. (NEPRIExTol-HF Trial, ClinicalTrials.gov number, NCT03190304)., (Copyright © 2021. Published by Elsevier Inc.)

Aims: We studied the association between android (A) to gynoid (G) fat ratio and functional capacity (peak VO 2 ) 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 VO 2 (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/m 2 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 VO 2 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 VO 2 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., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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/m 2 , -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/m 2 were more likely to be identified by Baumgartner's than Studenski's method (P < 0.001). However, in patients with BMI ≥ 25 kg/m 2 , 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., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Purpose: Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy associated with low functional capacity and high mortality rates. Exercise training has been proved to be a nonpharmacological treatment of cardiovascular diseases. Therefore, the purpose of this study was to determine the effects of exercise rehabilitation in EMF patients., Methods: Twenty-two EMF patients, functional classes II and III (New York Heart Association [NYHA]), were randomized to the control (C-EMF) or exercise rehabilitation (Rehab-EMF) group. Patients in the Rehab-EMF group underwent 4 mo of exercise rehabilitation, whereas patients in the C-EMF group were instructed to maintain their usual daily routine. Peak oxygen uptake ((Equation is included in full-text article.)O2), cardiac function, and quality of life were evaluated. All assessments were performed at baseline and after 4 mo., Results: After 4 mo of rehabilitation, peak (Equation is included in full-text article.)O2 increased in the Rehab-EMF group (17.4 ± 3.0 to 19.7 ± 4.4 mL/kg/min, P < .001), whereas the C-EMF group showed no difference (15.3 ± 3.0 to 15.0 ± 2.0 mL/kg/min, P = .87). Also, post-intervention, peak (Equation is included in full-text article.)O2 in the Rehab-EMF group was greater than that in the C-EMF group (P < .001). Furthermore, the Rehab-EMF group, when compared to the C-EMF group, showed an increase in left ventricular end-diastolic volume (102.1 ± 64.6 to 136.2 ± 75.8 mL vs 114.4 ± 55.0 to 100.4 ± 49.9 mL, P < .001, respectively) and decrease in left atrial diastolic volume (69.0 ± 33.0 to 34.9 ± 15.0 mL vs 44.6 ± 21.0 to 45.6 ± 23.0 mL, P < .001, respectively). Quality-of-life scores also improved in the Rehab-EMF group, whereas the C-EMF group showed no change (45 ± 23 to 27 ± 15 vs 47 ± 15 to 45 ± 17, P < .001, respectively)., Conclusion: Exercise rehabilitation is a nonpharmacological intervention that improves functional capacity, cardiac volumes, and quality of life in EMF patients after endocardial resection surgery. In addition, exercise rehabilitation should be prescribed to EMF patients to improve their clinical condition.

Objectives: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels., Methods: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device., Results: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity., Conclusions: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

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.