Abnormal neurovascular control during central and peripheral chemoreceptors stimulation in heart failure patients with preserved ejection fraction.

PURPOSE: Central and peripheral chemoreceptors are hypersensitized in patients with heart failure with reduced ejection fraction. Whether this autonomic alteration occurs in patients with heart failure with preserved ejection fraction (HFpEF) remains little known. We test the hypothesis that the central and peripheral chemoreflex control of muscle sympathetic nerve activity (MSNA) is altered in HFpEF. METHODS: Patients aged 55-80 years with symptoms of heart failure, body mass index ≤ 35 kg/m2, left ventricular ejection fraction > 50%, left atrial volume index > 34 mL/m2, left ventricular early diastolic filling velocity and early diastolic tissue velocity of mitral annulus ratio (E/e' index) ≥ 13, and BNP levels > 35 pg/mL were included in the study (HFpEF, n = 9). Patients without heart failure with preserved ejection fraction (non-HFpEF, n = 9), aged-paired, were also included in the study. Peripheral chemoreceptors stimulation (10% O2 and 90% N2, with CO2 titrated) and central chemoreceptors stimulation (7% CO2 and 93% O2) were conducted for 3 min. MSNA was evaluated by microneurography technique, and forearm blood flow (FBF) by venous occlusion plethysmography. RESULTS: During hypoxia, MSNA responses were greater (p < 0.001) and FBF responses were lower in patients with HFpEF (p = 0.006). Likewise, MSNA responses during hypercapnia were higher (p < 0.001) and forearm vascular conductance (FVC) levels were lower (p = 0.030) in patients with HFpEF. CONCLUSIONS: Peripheral and central chemoreflex controls of MSNA are hypersensitized in patients with HFpEF, which seems to contribute to the increase in MSNA in these patients. In addition, peripheral and central chemoreceptors stimulation in patients with HFpEF causes muscle vasoconstriction.

Effects of inspiratory muscle training combined with aerobic exercise training on neurovascular control in chronic heart failure patients.

AIMS: We tested the hypothesis that the effects of combined inspiratory muscle training and aerobic exercise training (IMT + AET) on muscle sympathetic nerve activity (MSNA) and forearm blood flow in patients with heart failure with reduced ejection fraction are more pronounced than the effects of AET alone. METHODS AND RESULTS: Patients aged 30-70 years, New York Heart Association Functional Class II-III, and left ventricular ejection fraction ≤40% were randomly assigned to four groups: IMT (n = 11), AET (n = 12), IMT + AET (n = 9), and non-training (NT; n = 10). MSNA was recorded using microneurography. Forearm blood flow was measured by venous occlusion plethysmography and inspiratory muscle strength by maximal inspiratory pressure. IMT consisted of 30 min sessions, five times a week, for 4 months. Moderate AET consisted of 60 min sessions, three times a week for 4 months. AET (-10 ± 2 bursts/min, P = 0.03) and IMT + AET (-13 ± 4 bursts/min, P = 0.007) reduced MSNA. These responses in MSNA were not different between AET and IMT + AET groups. IMT (0.22 ± 0.08 mL/min/100 mL, P = 0.03), AET (0.27 ± 0.09 mL/min/100 mL, P = 0.01), and IMT + AET (0.35 ± 0.12 mL/min/100 mL, P = 0.008) increased forearm blood flow. No differences were found between groups. AET (3 ± 1 mL/kg/min, P = 0.006) and IMT + AET (4 ± 1 mL/kg/min, P = 0.001) increased peak oxygen consumption. These responses were similar between these groups. IMT (20 ± 3 cmH2 O, P = 0.005) and IMT + AET (18 ± 3 cmH2 O, P = 0.01) increased maximal inspiratory pressure. No significant changes were observed in the NT group. CONCLUSIONS: IMT + AET causes no additive effects on neurovascular control in patients with heart failure with reduced ejection fraction compared with AET alone. These findings may be, in part, because few patients had inspiratory muscle weakness.

Effect of exercise training on cardiovascular autonomic and muscular function in subclinical Chagas cardiomyopathy: a randomized controlled trial.

PURPOSE: Patients with chronic chagasic cardiomyopathy with preserved ventricular function present with autonomic imbalance. This study evaluated the effects of exercise training (ET) in restoring peripheral and cardiac autonomic control and skeletal muscle phenotype in patients with subclinical chronic chagasic cardiomyopathy. METHODS: This controlled trial (NCT02295215) included 24 chronic chagasic cardiomyopathy patients who were randomized www.random.org/lists/ into two groups: those who underwent exercise training (n = 12) and those who continued their usual activities (n = 12). Eight patients completed the exercise training protocol, and 10 patients were clinically followed up for 4 months. Muscular sympathetic nerve activity was measured by microneurography and muscle blood flow (MBF) using venous occlusion plethysmography. The low-frequency component of heart rate variability in normalized units (LFnuHR) reflects sympathetic activity in the heart, and the low-frequency component of systolic blood pressure variability in normalized units reflects sympathetic activity in the vessels. The infusion of vasoactive drugs (phenylephrine and sodium nitroprusside) was used to evaluate cardiac baroreflex sensitivity, and a vastus lateralis muscle biopsy was performed to evaluate atrogin-1 and MuRF-1 gene expression. RESULTS: The baroreflex sensitivity for increases (p = 0.002) and decreases (p = 0.02) in systolic blood pressure increased in the ET group. Muscle blood flow also increased only in the ET group (p = 0.004). Only the ET group had reduced resting muscular sympathetic nerve activity levels (p = 0.008) and sympathetic activity in the heart (LFnu; p = 0.004) and vessels (p = 0.04) after 4 months. Regarding skeletal muscle, after 4 months, participants in the exercise training group presented with lower atrogin-1 gene expression than participants who continued their activities as usual (p = 0.001). The reduction in muscular sympathetic nerve activity was positively associated with reduced atrogin-1 (r = 0.86; p = 0.02) and MuRF-1 gene expression (r = 0.64; p = 0.06); it was negatively associated with improved baroreflex sensitivity both for increases (r = -0.72; p = 0.020) and decreases (r = -0.82; p = 0.001) in blood pressure. CONCLUSIONS: ET improved cardiac and peripheral autonomic function in patients with subclinical chagasic cardiomyopathy. ET reduced MSNA and sympathetic activity in the heart and vessels and increased cardiac parasympathetic tone and baroreflex sensitivity. Regarding peripheral muscle, after 4 months, patients who underwent exercise training had an increased cross-sectional area of type I fibers and oxidative metabolism of muscle fibers, and decreased atrogin-1 gene expression, compared to participants who continued their activities as usual. In addition, the reduction in MSNA was associated with improved cardiac baroreflex sensitivity, reduced sympathetic cardiovascular tone, and reduced atrogin-1 and MuRF-1 gene expression. TRIAL REGISTRATION: ID: NCT02295215. Registered in June 2013.

Pre-frailty status increases the risk of rehospitalization in patients after elective cardiac surgery without complication.

BACKGROUND AND AIM: It has been demonstrated that patients with pre-frailty have more adverse outcomes after cardiac surgery; however, data on prognosis and long-term evolution in patients with pre-frailty after elective cardiac surgery without postoperative complications are still scarce. To evaluate the impact of pre-frailty status on functional survival in patients after elective cardiac surgery without surgical complications. METHODS: This was a retrospective study with 141 patients over 65 years old, with an established diagnosis of myocardial infarction or valve disease. Patients were evaluated by Clinical Frailty Scale (CFS) before surgery, according to the hospital protocol, and allocated into two groups: non-frail (CFS, 1-3) and pre-frail (CFS = 4). Patients with adverse cardiovascular events during surgery or at intensive care unit (ICU), mechanical ventilation more than 24 hours, ICU length of stay more than 48 hours, and in-hospital complications were excluded. For all analyses, the statistical significance was set at 5% (P < .05). RESULTS: There were no differences in demographic, anthropometric, surgical procedure, or baseline data on ICU. Pre-frail patients had more adverse events during the 3-year follow-up period with rehospitalization compared to non-frail (39.4% vs 14.3%, respectively). Rehospitalizations in pre-frail patients were in the first year after cardiac surgery (P < .05), and higher cumulative events in pre-frail have occurred with increased odds ratio (OR) (2.828, 95% confidence interval [CI]: 1.298-6.160; P = .001) and hazard ratio (HR) (3.560, 95% CI: 1.508-84.04; P = .004). The OR and HR for stroke or death were similar between groups when analyzed separately. CONCLUSION: Pre-frail patients have more adverse events after elective cardiac surgery without complications when compared to non-frail patients.

Safety and Efficacy of Aerobic Exercise Training Associated to Non-Invasive Ventilation in Patients with Acute Heart Failure / Segurança e Eficácia do Treinamento Aeróbio Combinado à Ventilação Não-Invasiva em Pacientes com Insuficiência Cardíaca Aguda

Abstract Background: Exercise training (ET) improves functional capacity in chronic heart failure (HF). However, ET effects in acute HF are unknown. Objective: To investigate the effects of ET alone or combined with noninvasive ventilation (NIV) compared with standard medical treatment during hospitalization in acute HF patients. Methods: Twenty-nine patients (systolic HF) were randomized into three groups: control (Control - only standard medical treatment); ET with placebo NIV (ET+Sham) and ET+NIV (NIV with 14 and 8 cmH2O of inspiratory and expiratory pressure, respectively). The 6MWT was performed on day 1 and day 10 of hospitalization and the ET was performed on an unloaded cycle ergometer until patients' tolerance limit (20 min or less) for eight consecutive days. For all analyses, statistical significance was set at 5% (p < 0.05). Results: None of the patients in either exercise groups had adverse events or required exercise interruption. The 6MWT distance was greater in ET+NIV (Δ120 ± 72 m) than in ET+Sham (Δ73 ± 26 m) and Control (Δ45 ± 32 m; p < 0.05). Total exercise time was greater (128 ± 10 vs. 92 ± 8 min; p < 0.05) and dyspnea was lower (3 ± 1 vs. 4 ± 1; p < 0.05) in ET+NIV than ET+Sham. The ET+NIV group had a shorter hospital stay (17 ± 10 days) than ET+Sham (23 ± 8 days) and Control (39 ± 15 days) groups (p < 0.05). Total exercise time in ET+Sham and ET+NIV had significant correlation with length of hospital stay (r = -0.75; p = 0.01). Conclusion: Exercise training in acute HF was safe, had no adverse events and, when combined with NIV, improved 6MWT and reduce dyspnea and length of stay.

Resumo Fundamento: O exercício físico melhora a capacidade funcional em pacientes com insuficiência cardíaca (IC) crônica. Entretanto, os efeitos do exercício na IC aguda são desconhecidos. Objetivo: Investigar os efeitos do exercício físico isolado ou associado à ventilação não-invasiva (VNI) em comparação ao tratamento convencional em pacientes com IC durante internação. Métodos: Vinte e nove pacientes (IC sistólica) foram randomizados em três grupos: Controle (tratamento clínico convencional); exercício com ventilação placebo (EX+Sham) e EX+VNI (VNI com 14 e 8 cmH2O de pressão inspiratória e expiratória, respectivamente).O TC6M foi realizado no primeiro e no décimo dia de internação e o exercício realizado em cicloergômetro até o limite de tolerância (20 minutos ou menos) por oito dias consecutivos. Para todas as análises, foi considerado p < 0,05 estatisticamente significante. Resultados: Nenhum paciente dos grupos EX+Sham e EX+VNI apresentou complicações ou necessitou interromper o exercício. O grupo EX+VNI apresentou melhor desempenho no TC6M (Δ120 ± 72 m) que os grupos EX+Sham (Δ73 ± 26 m) e Controle (Δ45 ± 32 m; p < 0,05). O tempo total de exercício foi maior (128 ± 10 vs. 92 ± 8 min; p < 0,05) e a dispneia menor (3 ± 1 vs. 4 ± 1; p < 0,05) no EX+VNI em relação ao EX+Sham. O grupo EX+VNI apresentou menor tempo de internação (17 ± 10 dias) comparado ao EX+Sham (23 ± 8 dias) e Controle (39 ± 15 dias; p < 0,05). O tempo total de exercício nos grupos EX+Sham e EX+VNI correlacionou-se com o tempo de internação hospitalar (r = -0,75; p = 0,01). Conclusão: O exercício físico foi seguro em pacientes com IC aguda, não houve complicações hospitalares e, quando associada à VNI, melhorou o desempenho no TC6M, dispneia e o tempo de internação.

Pre-Frailty Increases the Risk of Adverse Events in Older Patients Undergoing Cardiovascular Surgery / Pré-Fragilidade Aumenta o Risco de Eventos Adversos em Idosos Submetidos à Cirurgia Cardiovascular

Abstract Background: Frailty is identified as a major predictor of adverse outcomes in older surgical patients. However, the outcomes in pre-frail patients after cardiovascular surgery remain unknown. Objective: To investigate the main outcomes (length of stay, mechanical ventilation time, stroke and in-hospital death) in pre-frail patients in comparison with no-frail patients after cardiovascular surgery. Methods: 221 patients over 65 years old, with established diagnosis of myocardial infarction or valve disease were enrolled. Patients were evaluated by Clinical Frailty Score (CFS) before surgery and allocated into 2 groups: no-frailty (CFS 1~3) vs. pre-frailty (CFS 4) and followed up for main outcomes. For all analysis, the statistical significance was set at 5% (p < 0.05). Results: No differences were found in anthropometric and demographic data between groups (p > 0.05). Pre-frail patients showed a longer mechanical ventilation time (193 ± 37 vs. 29 ± 7 hours; p<0.05) than no-frail patients; similar results were observed for length of stay at the intensive care unit (5 ± 1 vs. 3 ± 1 days; p < 0.05) and total time of hospitalization (12 ± 5 vs. 9 ± 3 days; p < 0.05). In addition, the pre-frail group had a higher number of adverse events (stroke 8.3% vs. 3.9%; in-hospital death 21.5% vs. 7.8%; p < 0.05) with an increased risk for development stroke (OR: 2.139, 95% CI: 0.622-7.351, p = 0.001; HR: 2.763, 95%CI: 1.206-6.331, p = 0.0001) and in-hospital death (OR: 1.809, 95% CI: 1.286-2.546, p = 0.001; HR: 1.830, 95% CI: 1.476-2.269, p = 0.0001). Moreover, higher number of pre-frail patients required homecare services than no-frail patients (46.5% vs. 0%; p < 0.05). Conclusion: Patients with pre-frailty showed longer mechanical ventilation time and hospital stay with an increased risk for cardiovascular events compared with no-frail patients.

Resumo Fundamentos: A fragilidade é reconhecida como um importante preditor de eventos adversos em pacientes cirúrgicos idosos. Entretanto, os desfechos em pacientes com pré-fragilidade após a cirurgia cardiovascular ainda permanecem desconhecidos. Objetivos: Investigar os principais desfechos (tempo de internação, tempo de ventilação mecânica, incidência de acidente vascular cerebral e óbito intra-hospitalar) após cirurgia cardiovascular em pacientes com pré-fragilidade em comparação a pacientes sem fragilidade. Métodos: 221 pacientes acima de 65 anos de idade, com diagnóstico de infarto do miocárdio ou doença valvar foram recrutados no estudo. Os pacientes foram avaliados pela escala de fragilidade clínica (CFS, Clinical Frailty Score) antes da cirurgia e separados em 2 grupos: sem-fragilidade (CFS 1~3) vs. pré-fragilidade (CFS 4). Para todas as análises, foi considerada diferença significativa quando p < 0,05. Resultados: Não foram observadas diferenças nos dados antropométricos e demográficos entre os grupos. Os pacientes com pré-fragilidade apresentaram maior tempo de ventilação mecânica em comparação a pacientes sem fragilidade (193 ± 37 vs. 29 ± 7 horas; p < 0,05); resultados similares foram observados para tempo de permanência na unidade de terapia intensiva (5 ± 1 vs. 3 ± 1 days; p < 0,05) e tempo total de internação hospitalar (12 ± 5 vs. 9 ± 3 dias; p < 0,05). Além disso, os pacientes com pré-fragilidade apresentaram maior número de eventos adversos (acidente vascular cerebral-AVC 8,3% vs. 3,9%; óbito intra-hospitalar 21,5% vs. 7,8%; p<0,05) com risco aumentado para AVC (OR: 2,139, IC 95%: 0,622-7,351, p = 0,001; HR: 2,763, IC 95%: 1,206-6,331, p = 0,0001) e morte intra-hospitalar (OR: 1,809, IC 95%: 1,286-2,546, p = 0,001; HR: 1,830, IC 95%: 1,476-2,269, p = 0,0001). Além disso, um maior número de pacientes com pré-fragilidade necessitaram de fisioterapia domiciliar que pacientes sem fragilidade (46,5% vs. 0%; p< 0,05). Conclusão: Pacientes com pré-fragilidade apresentaram maior tempo de ventilação mecânica e maior tempo de internação hospitalar, com maior risco de desenvolverem eventos cardiovasculares adversos em comparação a pacientes sem fragilidade.

Pre-Frailty Increases the Risk of Adverse Events in Older Patients Undergoing Cardiovascular Surgery.

BACKGROUND: Frailty is identified as a major predictor of adverse outcomes in older surgical patients. However, the outcomes in pre-frail patients after cardiovascular surgery remain unknown. OBJECTIVE: To investigate the main outcomes (length of stay, mechanical ventilation time, stroke and in-hospital death) in pre-frail patients in comparison with no-frail patients after cardiovascular surgery. METHODS: 221 patients over 65 years old, with established diagnosis of myocardial infarction or valve disease were enrolled. Patients were evaluated by Clinical Frailty Score (CFS) before surgery and allocated into 2 groups: no-frailty (CFS 1~3) vs. pre-frailty (CFS 4) and followed up for main outcomes. For all analysis, the statistical significance was set at 5% (p < 0.05). RESULTS: No differences were found in anthropometric and demographic data between groups (p > 0.05). Pre-frail patients showed a longer mechanical ventilation time (193 ± 37 vs. 29 ± 7 hours; p<0.05) than no-frail patients; similar results were observed for length of stay at the intensive care unit (5 ± 1 vs. 3 ± 1 days; p < 0.05) and total time of hospitalization (12 ± 5 vs. 9 ± 3 days; p < 0.05). In addition, the pre-frail group had a higher number of adverse events (stroke 8.3% vs. 3.9%; in-hospital death 21.5% vs. 7.8%; p < 0.05) with an increased risk for development stroke (OR: 2.139, 95% CI: 0.622-7.351, p = 0.001; HR: 2.763, 95%CI: 1.206-6.331, p = 0.0001) and in-hospital death (OR: 1.809, 95% CI: 1.286-2.546, p = 0.001; HR: 1.830, 95% CI: 1.476-2.269, p = 0.0001). Moreover, higher number of pre-frail patients required homecare services than no-frail patients (46.5% vs. 0%; p < 0.05). CONCLUSION: Patients with pre-frailty showed longer mechanical ventilation time and hospital stay with an increased risk for cardiovascular events compared with no-frail patients.

Alternatives to Aerobic Exercise Prescription in Patients with Chronic Heart Failure / Alternativas para Prescrição de Exercício Aeróbio a Pacientes com Insuficiência Cardíaca

Background: Exercise is essential for patients with heart failure as it leads to a reduction in morbidity and mortality as well as improved functional capacity and oxygen uptake (v̇O2). However, the need for an experienced physiologist and the cost of the exam may render the cardiopulmonary exercise test (CPET) unfeasible. Thus, the six-minute walk test (6MWT) and step test (ST) may be alternatives for exercise prescription. Objective: The aim was to correlate heart rate (HR) during the 6MWT and ST with HR at the anaerobic threshold (HRAT) and peak HR (HRP) obtained on the CPET. Methods: Eighty-three patients (58 ± 11 years) with heart failure (NYHA class II) were included and all subjects had optimized medication for at least 3 months. Evaluations involved CPET (v̇O2, HRAT, HRP), 6MWT (HR6MWT) and ST (HRST). Results: The participants exhibited severe ventricular dysfunction (ejection fraction: 31 ± 7%) and low peak v̇O2 (15.2 ± 3.1 mL.kg-1.min-1). HRP (113 ± 19 bpm) was higher than HRAT (92 ± 14 bpm; p < 0.05) and HR6MWT (94 ± 13 bpm; p < 0.05). No significant difference was found between HRP and HRST. Moreover, a strong correlation was found between HRAT and HR6MWT (r = 0.81; p < 0.0001), and between HRP and HRST (r = 0.89; p < 0.0001). Conclusion: These findings suggest that, in the absence of CPET, exercise prescription can be performed by use of 6MWT and ST, based on HR6MWT and HRST.

Fundamento: O exercício físico é fundamental para pacientes com insuficiência cardíaca, pois reduz a morbimortalidade e melhora a capacidade funcional e o consumo de oxigênio (v̇O2). Entretanto, a realização do teste de exercício cardiopulmonar (TECP) pode se tornar inviável, devido à necessidade de médico capacitado e ao alto custo deste exame. Assim, o teste de caminhada de 6 minutos (TC6M) e o teste do degrau (TD) emergem como alternativas para a prescrição de exercício. Objetivo: Correlacionar a frequência cardíaca (FC) durante o TC6M e o TD com a FC no limiar aeróbio (FCLA) e a FC no pico do exercício (FCP), obtidas no TECP. Métodos: Foram incluídos 83 pacientes (58 ± 11 anos) com insuficiência cardíaca (NYHA classe II), com medicação otimizada por pelo menos 3 meses. Foram realizados TECP (v̇O2, FCLA e FCP), TC6M (FCTC6M) e TD (FCTD). Resultados: Os pacientes apresentavam disfunção ventricular grave (fração de ejeção: 31 ± 7%) e baixo v̇O2 pico (15,2 ± 3,1 ml.kg-1.min-1). A FCP (113 ± 19 bpm) foi maior que a FCLA (92 ± 14 bpm; p < 0,05) e a FCTC6M (94 ± 13 bpm; p < 0,05). Não houve diferença entre FCP e FCTD. Além disso, observou-se forte correlação entre a FCLA e a FCTC6M (r = 0,81; p < 0,0001) e entre a FCP e a FCTD (r = 0,89; p < 0,0001). Conclusão: Os resultados obtidos sugerem ser viável a prescrição de exercício através do TC6M e do TD, com base na FCTC6M e na FCTD, na ausência do TECP.