Produção Nacional
Revisado por pares
High-Intensity Interval Training Decreases Muscle Sympathetic Nerve Activity and Improves Peripheral Vascular Function in Patients With Heart Failure With Reduced Ejection Fraction
2020; Lippincott Williams & Wilkins; Volume: 13; Issue: 8 Linguagem: Inglês
10.1161/circheartfailure.120.007121
ISSN1941-3297
AutoresAllan R. K. Sales, Luciene Ferreira Azevedo, Thiago O. C. Silva, Amanda G. Rodrigues, Patrícia Oliveira, Camila Paixão Jordão, Ana Cristina Andrade, Úrsula Urias, Guilherme Veiga Guimarães, Edimar Alcides Bocchi, Maria Janieire N.N. Alves, Ludhmila Abrahão Hajjar, Roberto Kalil Filho, Zachary I. Grunewald, Luis A. Martinez‐Lemus, Jaume Padilla, Carlos Eduardo Negrão,
Tópico(s)Cardiac Health and Mental Health
ResumoHomeCirculation: Heart FailureVol. 13, No. 8High-Intensity Interval Training Decreases Muscle Sympathetic Nerve Activity and Improves Peripheral Vascular Function in Patients With Heart Failure With Reduced Ejection Fraction Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBHigh-Intensity Interval Training Decreases Muscle Sympathetic Nerve Activity and Improves Peripheral Vascular Function in Patients With Heart Failure With Reduced Ejection Fraction Allan R.K. Sales, PhD, Luciene F. Azevedo, PhD, Thiago O.C. Silva, MS, Amanda G. Rodrigues, MD, Patricia A. Oliveira, MD, Camila P. Jordão, MS, Ana C.M. Andrade, MD, PhD, Ursula Urias, PhD, Guilherme V. Guimaraes, PhD, Edimar A. Bocchi, MD, PhD, Maria Janieire N.N. Alves, MD, PhD, Ludhmila A. Hajjar, MD, PhD, Roberto K. Filho, MD, PhD, Zachary I. Grunewald, MS, RDN, Luis A. Martinez-Lemus, DVM, PhD, Jaume Padilla, PhD and Carlos E. Negrão, PhD Allan R.K. SalesAllan R.K. Sales Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). D'Or Institute for Research and Education (IDOR), São Paulo, Brazil (A.R.K.S.). , Luciene F. AzevedoLuciene F. Azevedo Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). , Thiago O.C. SilvaThiago O.C. Silva Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). , Amanda G. RodriguesAmanda G. Rodrigues Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). , Patricia A. OliveiraPatricia A. Oliveira Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). , Camila P. JordãoCamila P. Jordão Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). , Ana C.M. AndradeAna C.M. Andrade Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). , Ursula UriasUrsula Urias Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). Department of Medical Pharmacology Physiology (U.U., L.A.M.-.L.), University of Missouri, Columbia. , Guilherme V. GuimaraesGuilherme V. Guimaraes Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). , Edimar A. BocchiEdimar A. Bocchi Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). , Maria Janieire N.N. AlvesMaria Janieire N.N. Alves Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). , Ludhmila A. HajjarLudhmila A. Hajjar Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). , Roberto K. FilhoRoberto K. Filho Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). , Zachary I. GrunewaldZachary I. Grunewald Department of Nutrition and Exercise Physiology (Z.I.G., J.P.), University of Missouri, Columbia. Dalton Cardiovascular Research Center (Z.I.G., L.A.M.-.L., J.P.), University of Missouri, Columbia. , Luis A. Martinez-LemusLuis A. Martinez-Lemus Dalton Cardiovascular Research Center (Z.I.G., L.A.M.-.L., J.P.), University of Missouri, Columbia. Department of Medical Pharmacology Physiology (U.U., L.A.M.-.L.), University of Missouri, Columbia. , Jaume PadillaJaume Padilla Department of Nutrition and Exercise Physiology (Z.I.G., J.P.), University of Missouri, Columbia. Dalton Cardiovascular Research Center (Z.I.G., L.A.M.-.L., J.P.), University of Missouri, Columbia. and Carlos E. NegrãoCarlos E. Negrão Correspondence to: Carlos Eduardo Negrão, PhD, Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, São Paulo, SP CEP 05403-904, Brazil. Email E-mail Address: [email protected] https://orcid.org/0000-0003-4652-1226 Heart Institute (InCor), University of São Paulo Medical School, Brazil (A.R.K.S., L.F.A., T.O.C.S., A.G.R., P.A.O., C.P.J., A.C.M.A., U.U., G.V.G., E.A.B., M.J.N.N.A., L.A.H., R.K.F., C.E.N.). School of Physical Education and Sport, University of São Paulo, Brazil (C.E.N.). Originally published16 Jul 2020https://doi.org/10.1161/CIRCHEARTFAILURE.120.007121Circulation: Heart Failure. 2020;13:e007121Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: July 16, 2020: Ahead of Print Heart failure with reduced ejection fraction (HFrEF) is characterized by presence of increased sympathetic nerve activity and peripheral vasoconstriction.1 Despite initial compensatory effects to maintain cardiac output, long-term sympathetic activation further deteriorates cardiac function.1 The result is that muscle sympathetic nerve activity (MSNA) highly correlates with syndrome severity and mortality.2 Thus, reducing sympathoexcitation is a major therapeutic target for patients with HFrEF.Accumulating evidence indicates that moderate-intensity continuous training (MICT) reduces MSNA and improves vascular function in HFrEF.3,4 More recently, high-intensity interval training (HIIT) emerged as another strategy for patients with HFrEF.4,5 This exercise paradigm is safe, and current literature suggests that HIIT is superior to MICT for improving clinical outcomes.4,5 However, effects of HIIT on MSNA in patients with HFrEF are unknown. We tested the hypothesis that reductions in MSNA would be greater following HIIT than MICT and that these changes would correspond with improvements in peripheral vascular function in patients with HFrEF.This study was approved by the Institutional Review Board of the University of São Paulo, Medical School (Certificado de Apresentação de Apreciação Ética=32344314700000068) and registered as a clinical trial. The data, analytic methods, and study materials are available to other researchers at the Heart Institute (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, with Dr Negrão or Dr Sales ([email protected]). Outpatients with HFrEF (30–65 years), left ventricular ejection fraction ≤40%, functional classes II to III were randomized into HIIT (n=11), MICT (n=11), or no training (NT, n=8). Left ventricular ejection fraction was evaluated by 2-dimensional echocardiography. MSNA was assessed using microneurography and brachial artery flow-mediated dilation, brachial artery blood flow, and vascular conductance using ultrasonography. Blood pressure and heart rate (HR) were measured by plethysmography and peak oxygen uptake (peak VO2) by cardiopulmonary exercise test. Measurements were collected over 2 days in the following 5 days after completion of training. Exercise training was conducted under supervision. Both HIIT and MICT used a cycle ergometer, 3 sessions/wk for 12 weeks. Training sessions were matched for energy expenditure (ie, an isocaloric energy expenditure of 200 kcal/session). The HIIT protocol followed a progressive work-to-recovery program across the 12 weeks (1:1.5 ratio during month one, 1:1 ratio during month two; 1:0.67 ratio during month 3). The intensity of the HIIT session was based on the HR corresponding to 5% above the respiratory compensation point obtained in cardiopulmonary exercise test. The intensity of the MICT session was based on the HR between anaerobic threshold and respiratory compensation point.One-way ANOVA was used to compare baseline characteristics and absolute changes. Mixed design 2-way repeated-measures ANOVA was used to compare variables between groups before and after exercise training or NT. Fisher post hoc test was applied when significant F values were found. Pearson coefficient was used to assess the relationship between absolute changes in MSNA and brachial artery flow-mediated dilation. Data are presented as means±SEM. Significance was set at P<0.05.No significant differences between groups in age, body mass index, or sex were observed. In addition, no significant differences between groups in functional class, etiology, functional capacity, left ventricular ejection fraction, medications, blood pressure, and comorbidities were observed. HR was greater in the NT group compared with HIIT or MICT groups.Examples of nerve recordings from one patient in each group are shown in Figure [A]. HIIT and MICT significantly decreased MSNA relative to the NT group (interaction effect, P=0.0001, Figure [B]). Notably, changes in MSNA were greater in HIIT than in MICT and NT (HIIT, −19.3±3.3 bursts/100HB [95% CI, −26.3 to −12.3) versus MICT, −8.4±3.3 bursts/100HB [95% CI, −15.3 to −1.3] and NT, 3.4±3.8 bursts/100HB [95% CI, −4.6 to 11.5] group effect, P=0.001, Figure [C]). Nerve recordings were not measured in three of eleven patients in the HIIT and MICT groups, and 2 of 8 patients in NT group. MSNA presented in the Figure are from 8 patients in the HIIT and MICT groups and 6 patients in the NT group. HIIT and MICT significantly increased brachial artery flow-mediated dilation responses relative to the NT group (interaction effect, P=0.0007, Figure [D]), but the increase was more pronounced in HIIT participants (HIIT, 3.0±0.5% [95% CI, 2.0–4.0] versus MICT, 1.2±0.5% [95% CI, 0.2–2.2] and NT, −0.1±0.5% (95% CI, −1.3–1.0]), group effect, P=0.001, Figure [E]). Pearson correlation showed a negative association between brachial artery flow-mediated dilation changes and MSNA changes (r=−0.60, P=0.005) when data from all subjects were pooled. These findings demonstrate that our HIIT paradigm is highly effective in improving the neurovascular control in patients with HFrEF.Download figureDownload PowerPointFigure. Muscle sympathetic nerve activity (MSNA) and brachial artery flow-mediated dilation (BAFMD) in patients with heart failure with reduced ejection fraction before (pre) and after (post) their participation in one of three interventions, namely: no training (NT), high-intensity interval training (HIIT), or moderate-intensity continuous training (MICT).A, Examples of MSNA recordings. B, Individual data of MSNA incidence bursts, *vs pre, P<0.01. C, Absolute change (delta) of MSNA, *vs NT, P=0.0001 and †vs MICT, P=0.03. D, Individual data of BAFMD preintervention and postintervention, *P<0.01 vs pre and †P=0.03 vs post in the MICT group. E, Absolute change (delta) in BAFMD, *vs NT, P=0.0003 and †vs MICT, P=0.01. All values are expressed as means±SEM. HB indicates heart beats.Cardiopulmonary exercise test revealed that peak VO2, peak power, and duration of exercise increased similarly in HIIT and MICT (time effect, P<0.05). No significant changes in left ventricular ejection fraction, blood pressure, and HR were observed in the studied groups. HIIT and MICT groups had significant increases in brachial artery blood flow and vascular conductance relative to the NT group (interaction effect, P<0.05), but increases were more pronounced in HIIT participants. Baroreflex response, as measured by bivariate autoregressive analysis of MSNA, was not significantly different between groups.In conclusion, our findings demonstrate that 12 weeks of HIIT is superior to MICT in reducing MSNA and improving peripheral vascular function in patients with HFrEF, despite similar increases in exercise capacity. Accordingly, HIIT should be considered as potential therapy for improving neurovascular control and reducing cardiovascular risk in patients with HFrEF.Nonstandard Abbreviations and AcronymsHFrEFheart failure with reduced ejection fractionHIIThigh-intensity interval trainingHRheart rateMICTmoderate-intensity continuous trainingMSNAmuscle sympathetic nerve activityNTno trainingAcknowledgmentsWe appreciate the time and effort put in by all patients. We acknowledge the team of the Unit of Cardiovascular Rehabilitation and Exercise Physiology, and Unit Heart Failure at Heart Institute, University of São Paulo Medical School for their technical assistance and support.Sources of FundingThis study was supported by São Paulo Research Foundation (FAPESP; 2010/08990-1 and 2015/22814-5) and National Council for Scientific and Technological Development Edital Universal - CNPq no. 408743/2016-6. Dr Sales was supported by FAPESP (2014/11671-6 and 2017/25613-6). Drs Negrão and Guimaraes were supported by National Council for Scientific and Technological Development (303573/2015-5 and 301957/2017-7).DisclosuresNone.FootnotesFor Sources of Funding and Disclosures, see page 296.Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04248894.Correspondence to: Carlos Eduardo Negrão, PhD, Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, São Paulo, SP CEP 05403-904, Brazil. Email [email protected]usp.brReferences1. Lymperopoulos A, Rengo G, Koch WJ. Adrenergic nervous system in heart failure: pathophysiology and therapy.Circ Res. 2013; 113:739–753. doi: 10.1161/CIRCRESAHA.113.300308LinkGoogle Scholar2. Barretto AC, Santos AC, Munhoz R, Rondon MU, Franco FG, Trombetta IC, Roveda F, de Matos LN, Braga AM, Middlekauff HR, et al. 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Notarius C, Keir D, Badrov M, Millar P, Oh P and Floras J (2022) Autonomic modulation in heart failure patients by cardiopulmonary rehabilitation: who benefits?, European Journal of Preventive Cardiology, 10.1093/eurjpc/zwac106 Guimarães G, Ribeiro F, Castro R, Roque J, Machado A, Antunes-Correa L, Ferreira S and Bocchi E (2021) Effects of the exercise training on skeletal muscle oxygen consumption in heart failure patients with reduced ejection fraction, International Journal of Cardiology, 10.1016/j.ijcard.2021.08.050, 343, (73-79), Online publication date: 1-Nov-2021. Notarius C and Floras J (2021) Sympathetic neural responses in heart failure during exercise and after exercise training, Clinical Science, 10.1042/CS20201306, 135:4, (651-669), Online publication date: 26-Feb-2021. August 2020Vol 13, Issue 8 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/CIRCHEARTFAILURE.120.007121PMID: 32673501 Originally publishedJuly 16, 2020 Keywordsexercise trainingheart failuresympathetic activityendothelial functionvasoconstrictionPDF download Advertisement
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