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.

Galectin-3 Levels in Patients with Chronic Constrictive Pericarditis. / Galectina-3 em Pacientes com Pericardite Constritiva Crônica.

Background Galectin-3 (Gal-3) is a proinflammatory, profibrotic molecule implicated in the pathogenesis of heart failure. The role of Gal-3 in patients with chronic constrictive pericarditis (CCP) is not clear. Objective The aim of this study was to assess plasma Gal-3 in patients with CCP and correlate it with clinical, functional and histologic parameters. Methods We prospectively evaluated 25 symptomatic patients with CCP referred for pericardiectomy and 21 healthy controls. Patients underwent clinical assessment, Gal-3 and B-type natriuretic peptide (BNP) measurements, echocardiography, cardiac magnetic resonance imaging and cardiopulmonary exercise test (CPET) at baseline. Six months after pericardiectomy CPET was repeated. An alpha error < 5% was considered statistically significant, with a confidence interval of 95%. Results Twenty-five patients with a median age of 45 years were included. Etiology was mainly idiopathic (n = 19, 76%); and 14 (56%) patients had NYHA functional class III/IV. Median BNP and Gal-3 were 143 (89-209) pg/dL and 14.8 (9.7-17.2) ng/mL, respectively. Gal-3 levels were not significantly higher in CCP patients than in control (p = 0.22). There were no significant correlations of Gal-3 with BNP, echocardiographic and cardiac magnetic resonance measures and histological findings. After pericardiectomy, it was found a statistically significant correlation between Gal-3 and the CPTE measures test duration (r = -0.79; p < 0.001) and exercise time (r = -0.79; p < 0.001). Conclusions Patients with CCP had normal levels of Gal-3 as compared to the controls. Gal-3 did not correlate with morphological and functional measures before pericardiectomy. However, the associations between Gal-3 and exercise intolerance after pericardiectomy may suggest a role of Gal-3 in prognosis prediction after pericardiectomy. (Arq Bras Cardiol. 2020; 114(4):683-689).

Galectina-3 em pacientes com pericardite constritiva crônica / Galectin-3 Levels in Patients with Chronic Constrictive Pericarditis

FUNDAMENTO: A galectina-3 (Gal-3) é uma molécula pró-inflamatória e pró-fibrótica, envolvida na patogênese da insuficiência cardíaca. O papel da Gal-3 em pacientes com pericardite constritiva crônica (PCC) não está claro. OBJETIVO: O objetivo deste estudo foi avaliar os níveis de Gal-3 em pacientes com PCC e correlacioná-los com parâmetros clínicos, funcionais e histológicos. MÉTODOS: Nós avaliamos prospectivamente 25 pacientes sintomáticos com PCC agendados à pericardiectomia e 21 controles sadios. Os pacientes foram submetidos à avaliação clínica, medidas de Gal-3 e peptídeo natriurético do tipo B (BNP), ecocardiografia, ressonância magnética cardíaca e teste cardiopulmonar de exercício (TCPE) no período basal. Seis meses após a pericardiectomia, repetiu-se o TCPE. Um erro alfa < 5% foi considerado estatisticamente significativo, com um intervalo de confiança de 95%. RESULTADOS: Foram incluídos 25 pacientes com idade mediana de 45 anos. A etiologia foi principalmente idiopática (n = 19, 76%), e 14 (56%) apresentaram classe funcional New York Heart Association (NYHA) III/IV. Os valores medianos de BNP e Gal-3 foram 143 (89-209) pg/dL e 14,8 (9,7-17,2) ng/mL, respectivamente. Os níveis de Gal-3 não foram estatisticamente maiores nos pacientes com PCC que em controles (p = 0,22). Não foram encontradas correlações significativas da Gal-3 com BNP, medidas ecocardiográficas e de ressonância magnética cardíaca, e achados histológicos. Após a pericardiectomia, encontrou-se uma correlação estatisticamente significativa entre Gal-3 e medidas do TCPE ­ duração do teste (r = ­0,79; p < 0,001) e tempo de exercício (r = ­0,79; p < 0,001). CONCLUSÕES: Pacientes com PCC apresentaram níveis normais de Gal-3, quando comparados aos indivíduos controles. A Gal-3 não se correlacionou com medidas morfológicas e funcionais antes da pericardiectomia. No entanto, associações entre Gal-3 e intolerância ao exercício após pericardiectomia pode sugerir um papel da Gal-3 na predição de prognóstico após a pericardiectomia.

Impact of pericardiectomy on exercise capacity and sleep of patients with chronic constrictive pericarditis.

BACKGROUND: Heart failure is associated with exercise intolerance and sleep- disordered breathing; however, studies in patients with chronic constrictive pericarditis are scarce. The purpose of our study was to assess exercise capacity and sleep in patients with chronic constrictive pericarditis (CCP) undergoing a pericardiectomy. METHODS: We studied consecutive patients scheduled for pericardiectomy due to symptomatic CCP. Were performed quality of life (Minnesota Living with Heart Failure Questionnaire-MLHFQ) and sleep questionnaires (Epworth, Pittsburgh Sleep Quality Index-PSQI), serum B-type natriuretic peptide (BNP), serum C-reactive protein, transthoracic echocardiography, cardiopulmonary exercise test and overnight polysomnography immediately before and six months after pericardiectomy. RESULTS: Twenty-five patients (76% males, age: 45.5±13.8 years, body mass index: 24.9±3.7 kg/m2, left ventricular ejection fraction: 60±6%) with CCP (76% idiopathic, 12% tuberculosis) were studied. As compared to the preoperative period, pericardiectomy resulted in reduction in BNP (143 (83.5-209.5) vs 76 (40-117.5) pg/mL, p = 0.011), improvement in VO2 peak (18.7±5.6 vs. 25.2±6.3 mL/kg/min, p<0.001), quality of life (MLHFQ score 62 (43,5-77,5) vs. 18 (8,5-22), p<0,001) and sleep (PSQI score 7.8±4.1 vs. 4.7±3.7, p<0.001) and no significant change in sleep disordered breathing (apnea hypopnea index-AHI 15.6 (8.3-31.7) vs. 14.6 (5.75-29.9) events/h, p = 0.253). CONCLUSION: Patients with symptomatic CCP showed reduced exercise capacity and sleep-disordered breathing. After pericardiectomy, there was improvement in exercise capacity and neutral effect on sleep-disordered breathing.

Exercise Rehabilitation Improves Cardiac Volumes and Functional Capacity in Patients With Endomyocardial Fibrosis: A RANDOMIZED CONTROLLED TRIAL.

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.

Diminished cholesterol efflux mediated by HDL and coronary artery disease in young male anabolic androgenic steroid users.

BACKGROUND AND AIMS: Anabolic androgenic steroids (AAS) have been associated with coronary artery disease (CAD). AAS abuse leads to a remarkable decrease in high-density lipoprotein (HDL) plasma concentration, which could be a key factor in the atherosclerotic process. Moreover, not only the concentration of HDL, but also its functionality, plays a pivotal role in CAD. We tested the functionality of HDL by cholesterol efflux and antioxidant capacity. We also evaluated the prevalence of CAD in AAS users. METHODS: Twenty strength-trained AAS users (AASU) age 29 ±â€¯5 yr, 20 age-matched strength-trained AAS nonusers (AASNU), and 10 sedentary controls (SC) were enrolled in this cross-sectional study. Functionality of HDL was evaluated by 14C-cholesterol efflux and the ability of HDL in inhibiting LDL oxidation. Coronary artery was evaluated with coronary computed tomography angiography. RESULTS: Cholesterol efflux was lower in AASU compared with AASNU and SC (20 vs. 23 vs. 24%, respectively, p < 0.001). However, the lag time for LDL oxidation was higher in AASU compared with AASNU and SC (41 vs 13 vs 11 min, respectively, p < 0.001). We found at least 2 coronary arteries with plaques in 25% of AASU. None of the AASNU and SC had plaques. The time of AAS use was negatively associated with cholesterol efflux. CONCLUSIONS: This study indicates that AAS abuse impairs the cholesterol efflux mediated by HDL. Long-term AAS use seems to be correlated with lower cholesterol efflux and early subclinical CAD in this population.

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.

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.

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.

Testosterone Deficiency Increases Hospital Readmission and Mortality Rates in Male Patients with Heart Failure / Deficiência de Testosterona Aumenta Readmissão Hospitalar e Mortalidade em Pacientes do Sexo Masculino com Insuficiência Cardíaca

Background:Testosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown.Objective:We investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF.Methods:Total testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients.Results:Length of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58–4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67–8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23–8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001).Conclusion:These results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT.

Fundamento:A deficiência de testosterona na insuficiência cardíaca (IC) está associada à diminuição da capacidade de exercício e mortalidade, mas o seu impacto sobre as readmissões é incerto. Além disso, sua relação com a ativação simpática é desconhecida.Objetivo:O presente estudo investigou o papel dos níveis de testosterona nas reinternações hospitalares, na mortalidade e na atividade nervosa simpática em pacientes com IC.Métodos:A testosterona total (TT) e a testosterona livre (TL) foram medidas em 110 pacientes do sexo masculino hospitalizados, com fração de ejeção < 45% eclassificação funcional da New York Heart Association (NYHA) IV, qualificados em dois grupos: 66 com baixos níveis de testosterona (BT) e 44 com testosterona normal (TN). Hipogonadismo foi definido como TT < 300 ng/dL e TL < 131 pmol/L. A atividade nervosa simpática muscular (ANSM) foi gravada por microneurografia em uma subpopulação de 27 pacientes.Resultados:O tempo de permanência hospitalar foi maior em pacientes BT em comparação com pacientes TN (37 ± 4 vs. 25 ± 4 dias; p = 0,008). Da mesma forma, o risco cumulativo de readmissão no período de um ano foi maior em pacientes BT (44% vs. 22%, p = 0,001). Na análise de uma única variável preditora, a testosterona total (HR = 2,77, IC 95% 1,58-4,85, p = 0,02) previu readmissão hospitalar no prazo de 90 dias. Na análise de uma única variável preditora, testosterona total (HR = 4,65, IC 95% 2,67-8,10, p = 0,009) e readmissão dentro de 90 dias (HR = 3,27, IC 95% 1,23-8,69, p = 0,02) previram aumento de mortalidade. Ativação neuro-humoral, estimada pela ANSM, foi significativamente maior nos pacientes BT em comparação aos do grupo TN (65 ± 3 vs. 51 ± 4 disparos/100BC; p < 0,001).Conclusão:Estes resultados sustentam o conceito de que BT é um fator de risco independente para a readmissão hospitalar dentro de 90 dias e para aumento de mortalidade em pacientes com IC. Além disso, observou-se aumento da ANSM em pacientes com baixos níveis de testosterona.

Testosterone deficiency increases hospital readmission and mortality rates in male patients with heart failure.

BACKGROUND: Testosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown. OBJECTIVE: We investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF. METHODS: Total testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients. RESULTS: Length of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58-4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67-8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23-8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001). CONCLUSION: These results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT.