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

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Abstract

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.

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Abbreviations

CCC:

Chronic chagasic cardiomyopathy

MSNA:

Muscle sympathetic nerve activity

ET:

Exercise training

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Funding

This study was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP-#2010/50048–1 and #2011/17533-6) and, in part, by Fundação Zerbini. AOS was supported by Conselho Nacional de Pesquisa and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CNPq, #142179/2013-2 and CAPES, 88881.135917/2016-01). LMAC was supported by FAPESP (#2013/15651-7). DMLL was supported by Conselho Nacional de Pesquisa (CNPq #140265/2013-9). CEN and MUPBR were supported by CNPq (#301867/2010-0 and #308068/2011-4, respectively).

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Authors and Affiliations

  1. Heart Institute (InCor), Unidade de Reabilitação Cardiovascular E Fisiologia Do Exercício, University of Sao Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar, 44, Cerqueira César, São Paulo, SP, CEP 05403-000, Brazil

    Adriana Oliveira Sarmento, Ligia M. Antunes-Correa, Maria J. N. N. Alves, Keila C. B. Fonseca, Fernanda G. Pessoa, Denise M. L. Lobo, Leila D. P. Moreira, Marcelo L. C. Vieira, Felix J. A. Ramires, Charles Mady, Carlos E. Negrao & Barbara M. Ianni

  2. School of Physical Education and Sports, University of Sao Paulo, Sao Paulo, Brazil

    Aline V. N. Bacurau, Maria U. P. B. Rondon, Eduardo Rondon, Patricia C. Brum & Carlos E. Negrao

  3. Universidade Nove de Julho, Sao Paulo, Brazil

    Ivani C. Trombetta

  4. Associate Post-Graduate Program in Physical Education University of Pernambuco, Federal University of Paraiba, Joao Pessoa, Brazil

    Maria Socorro do Brasileiro-Santos

  5. Faculty of Kinesiology and Physical Education of University of Toronto, Toronto, Canada

    Scott Thomas

Authors
  1. Adriana Oliveira Sarmento
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  2. Ligia M. Antunes-Correa
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  3. Maria J. N. N. Alves
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  4. Aline V. N. Bacurau
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Correspondence to Adriana Oliveira Sarmento.

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Sarmento, A.O., Antunes-Correa, L.M., Alves, M.J.N.N. et al. Effect of exercise training on cardiovascular autonomic and muscular function in subclinical Chagas cardiomyopathy: a randomized controlled trial. Clin Auton Res 31, 239–251 (2021). https://doi.org/10.1007/s10286-020-00721-1

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