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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">S337kp3z5hWCJKPM3yTZXvJ</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2018000100091</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20180002</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Viewpoint</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Cognitive Deficit in Heart Failure and the Benefits of Aerobic Physical Activity</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>R&#234;go</surname>
            <given-names>Maria Lu&#237;za de Medeiros</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="aff" rid="aff2"/>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cabral</surname>
            <given-names>Daniel Aranha Rego</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fontes</surname>
            <given-names>Eduardo Bodnariuc</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="aff" rid="aff2"/>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <institution content-type="orgname">Universidade Federal do Rio Grande do Norte</institution>
        <addr-line>
          <named-content content-type="city">Natal</named-content>
          <named-content content-type="state">RN</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Federal do Rio Grande do Norte (UFRN); NeuroEx, Natal, RN - Brazil</institution>
        <institution content-type="normalized">Universidade Federal do Rio Grande do Norte</institution>
      </aff>
      <aff id="aff2">
        <institution content-type="orgname">NeuroEx</institution>
        <addr-line>
          <named-content content-type="city">Natal</named-content>
          <named-content content-type="state">RN</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Maria Lu&#237;za de Medeiros R&#234;go,</bold> Rua Raimundo Chaves, 1652, F5. Postal Code 59064-390, Candel&#225;ria, Natal, RN - Brazil. E-mail: <email>marialuizamedeirosr@gmail.com</email>, <email>eduardobfontes@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research, Writing of the manuscript and Critical revision of the manuscript for intellectual content: R&#234;go MLM, Cabral DAR, Fontes EB.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <month>01</month>
        <year>2018</year>
      </pub-date>
      <volume>110</volume>
      <issue>1</issue>
      <fpage>91</fpage>
      <lpage>94</lpage>
      <history>
        <date date-type="received">
          <day>17</day>
          <month>06</month>
          <year>2017</year>
        </date>
        <date date-type="rev-recd">
          <day>30</day>
          <month>08</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>25</day>
          <month>09</month>
          <year>2017</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <p>Heart Failure is a clinical syndrome prevalent throughout the world and a major contribution to mortality of cardiac patients in Brazil. In addition, this pathology is strongly related to cerebral dysfunction, with a high prevalence of cognitive impairment. Many mechanisms may be related to cognitive loss, such as cerebral hypoperfusion, atrophy and loss of gray matter of the brain, and dysfunction of the autonomic nervous system. The literature is clear regarding the benefits of aerobic physical activity in healthy populations in the modulation of the autonomic nervous system and in brain functions. Studies have shown that in the population of patients with heart failure, exercise is associated with an improvement in cognitive function, as well as in cardiac autonomic regulation. However, little emphasis has been given to the mechanisms by which aerobic physical activity can benefit brain functioning, the autonomic nervous system and result in better cognitive performance, particularly in patients with heart failure. Therefore, the present work presents the ways in which brain areas responsible for cognition also act in the modulation of the autonomic nervous system, and emphasizes its importance for the understanding of cognitive impairment in relation to the pathophysiology of heart failure. It is also described the way in which aerobic physical activity can promote benefits when it is integrated into the therapy, associated to a better prognosis of the clinical picture of these patients.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Heart Failure</kwd>
        <kwd>Indicators of Morbidity and Mortality</kwd>
        <kwd>Cognition</kwd>
        <kwd>Exercise</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <p>Heart Failure (HF) accounts for about 50% of all hospitalizations occurring in South America<xref ref-type="bibr" rid="B1">1</xref> and is one of the most frequent causes of hospitalization for cardiovascular diseases.<xref ref-type="bibr" rid="B2">2</xref> In addition to the direct influence on cardiac autonomic control, HF is strongly related to the presence of cerebral dysfunction and cognitive impairment, affecting approximately 75% of this population.<xref ref-type="bibr" rid="B3">3</xref> This cognitive deficit is associated with executive functions, including difficulties in the planning and execution of actions, low ability to solve problems and inhibit behaviors.<xref ref-type="bibr" rid="B4">4</xref> In practice, this results into less ability to perform daily activities such as shopping, feeding and locomotion - including walking - in addition to being related to lower self-care levels, higher hospitalization rates, increased expenses with more frequent hospitalizations, and, finally, there is an increase in morbidity and mortality in this pathology. In this sense, several treatments are performed in order to mitigate the deleterious effects caused by HF. However, such treatments usually involve invasive and / or medicamentous procedures such as heart transplantation, left ventricular assist device, beta-blockers, aldosterone antagonists, and angiotensin converting enzyme inhibitors. All these drugs, despite having proven beneficial results, can develop several types of side effects such as renal failure and hyperpotassemia.<xref ref-type="bibr" rid="B2">2</xref> In this sense, physical exercise has been pointed out as an important auxiliary tool in the treatment of patients with HF, however, little has been analyzed about its benefits to brain function. In the present work, the pathways by which the prefrontal cortex (PFC) is closely linked to the regulation of cardiac autonomic control and its influence on cognitive impairment in HF patients are presented. In addition, it is described how the regular practice of physical activity can promote benefits to brain function and cognitive performance in this population, as well as the contribution on cardiac autonomic control already widely described.</p>
    <p>In the search for the genesis of this problem, many mechanisms may be related to cognitive loss, such as cerebral hypoperfusion, atrophy and loss of gray matter of the brain, as well as autonomic nervous system (ANS) dysfunction.<xref ref-type="bibr" rid="B5">5</xref> A neuroimaging study in FC II patients found that individuals with this syndrome had impairment in several brain areas such as the hippocampus (short-term memory conversion in long-term memory), caudate nucleus (modulation of body movements), PFC (executive functions: decision-making, planning, inhibitory control) and hypothalamus, fundamental areas in cognitive processes and autonomic control.<xref ref-type="bibr" rid="B5">5</xref> In this perspective, it is worth mentioning the existence of a recent pathophysiological model of cognitive decline in this population, which states that a set of factors such as hypoperfusion, hypoxia, inflammatory cytokines increase, thromboembolic diseases and hemodynamic abnormalities can lead to brain mass atrophy, generating cognitive deficits.<xref ref-type="bibr" rid="B6">6</xref> Another important point to emphasize about the pathophysiology imposed by HF is the severe dysfunction in ANS, characterized by increased sympathetic tone and decreased parasympathetic<xref ref-type="bibr" rid="B7">7</xref> and may be related to vasoconstriction.<xref ref-type="bibr" rid="B8">8</xref> As a consequence of this autonomic balance with sympathetic overlap, there is difficulty in the arrival of blood in various systems of the body, including the brain. Cerebral hypoperfusion in patients with HF may lead to reduced functional capacity<xref ref-type="bibr" rid="B9">9</xref> and cognitive deficits.<xref ref-type="bibr" rid="B5">5</xref> More specifically, permanent impairment of cerebral perfusion and chronic ischemia in deep areas may result in cognitive impairment and difficulty performing routine activities. The hippocampus, for example, has neural plasticity in front of the lower supply of oxygen and may have decreased mass and possibly cause memory impairment.<xref ref-type="bibr" rid="B10">10</xref>
		</p>
    <p>It has been demonstrated that FC I-III patients have low cerebral blood flow (CBF) in the sitting position and this is related to low cardiac output, which can cause intense hypoperfusion in the accomplishment of simple tasks, such as the act of leaving a position lying to a sitting.<xref ref-type="bibr" rid="B9">9</xref> Therefore, with less supply of oxygen to the brain, cognitive impairments are virtually unavoidable. In addition, it has already been observed that the degree of cognitive dysfunction may serve as a predictor of cardiovascular complications in patients with HF. In the study, 246 FC II - IV patients performed the Montreal Cognitive Assessment to evaluate cognitive ability and it was shown that the worst performance in the test was those with the greatest possibilities of cardiovascular events in up to 180 days.<xref ref-type="bibr" rid="B11">11</xref> Thus, cognition seems to be closely related to the degree of cerebral oxygenation, and the more hypoperfused the brain, the greater the dysfunction of the nervous system, indicating a greater impairment in cardiac output and a lower ability to modulate autonomic activity, increasing the risk of cardiovascular and cerebrovascular events.</p>
    <p>Literature is clear on the benefits of aerobic physical activity (APA) in healthy populations, on SNA modulation, and on brain and cognitive functions. Evidence shows that chronically performed APA has the potential to promote beneficial effects on cardiovascular health, mediated by increased vagal tone and decreased sympathetic activity in the sinus node, with improved vascular function, cardiac remodeling, and renal-adrenal functions.<xref ref-type="bibr" rid="B12">12</xref> However, regular APA has also demonstrated an important role in the modulation of some brain regions of fundamental importance in cognitive processes, through the increase of CBF in PFC,<xref ref-type="bibr" rid="B13">13</xref> increased volume in the hippocampus,<xref ref-type="bibr" rid="B10">10</xref> increased concentrations of vascular endothelial growth factors (VEGF) (new capillary growth) and brain-derived neurotrophic factor (BDNF) (strengthening of synaptic connections)<xref ref-type="bibr" rid="B14">14</xref>, as well as angiogenesis in lobofrontal regions.<xref ref-type="bibr" rid="B15">15</xref> Therefore, these functional, biochemical, and morphological changes in the brain are strongly linked to cognitive improvement.</p>
    <p>Following this line of reasoning, in a study with FC III patients and ejection fraction &#8804; 35%, an 18 week intervention (twice a week) of physical exercises was performed alternating between treadmill, cycle ergometer and stair simulator. The results demonstrated that exercise improved the cognitive functions of selective attention and psychomotor speed.<xref ref-type="bibr" rid="B16">16</xref> In addition, the performance of the six-minute walk test and the Mini Mental State Exam score have been directly correlated, indicating that the lower the functional cardiovascular capacity of the subject, the lower their cognitive ability.<xref ref-type="bibr" rid="B17">17</xref> In the meantime, it is worth mentioning that patients usually leave the doctors' offices having heard that the practice of physical exercises is important to combat the sedentary lifestyle, improve the function of the heart muscle and, therefore, become healthier and with a better quality of life. However, the low emphasis on cognitive benefits and the improvement in brain function that physical activity can provide for HF patients is of concern.</p>
    <p>In this context, a recent review addresses the practice of APA as a beneficial factor in preventing and even reversing the cognitive impairment caused mainly by the decrease in CBF in this population. This benefit would be a consequence of both the improvement in cardiac muscle contractile activity and the decrease in peripheral vascular resistance due to a decrease in sympathetic activation.<xref ref-type="bibr" rid="B18">18</xref> Furthermore, the possible effects of APA on the ANS of patients with heart disease have been demonstrated, as in the case of HF, indicating the possible sympatovagal modulation with increased parasympathetic tone and a decrease in sympathetic activity, which is an extremely important and decisive clinical condition for this population.<xref ref-type="bibr" rid="B19">19</xref> However, little emphasis was given to the integration between the CBF and the autonomic nervous system, as well as in the modulation of the ANS as a result of exercise in patients with HF, besides the possible integration pathways resulting from this modulation of the ANS and its influence on activity in general, implying greater benefits for the individual.</p>
    <p>The pathways through which frontal regions, such as the PFC, act in the modulation of the ANS are important for the understanding of the pathophysiology of HF, as well as to understand how the APA can interfere in these two aspects (cognition and cardiac autonomic control). In this sense, a neurovisceral model was proposed by which the PFC has an inhibitory function on the amygdala<xref ref-type="bibr" rid="B20">20</xref> (an integrative area that receives sensory afferents, confers an emotional characteristic and emits eferences to cortical areas). However, when this region is uninhibited, a situation that can occur due to the lower CBF in the PFC, allows the activation of sympathetic neurons and a decrease in the action of parasympathetic neurons, both in the brainstem<xref ref-type="bibr" rid="B20">20</xref>, triggering a nervous autonomic balance with sympathetic predominance. It is known that APA plays an active role, especially in CPF<xref ref-type="bibr" rid="B13">13</xref> and autonomic modulation<xref ref-type="bibr" rid="B12">12</xref>, creating a feedback system in which APA acts in several spheres, culminating in the cognitive improvement of patients (<xref ref-type="fig" rid="f1">Figure 1</xref>) and, consequently, improving the prognosis.</p>
    <p>
      <fig id="f1">
        <label>Figure 1</label>
        <caption>
          <title>Aerobic physical activity promotes an increase in the concentrations of VEGF and BDNF, which can improve cognitive processes, increase the parasympathetic tone, and decrease the sympathetic activation. This condition may decrease peripheral vascular resistance and lead to increased cerebral blood flow in the prefrontal cortex, positively interfering with cognitive ability. With increased cerebral blood flow in the prefrontal cortex, there may be an inhibition of the amygdala promoting a vagal increase and sympathetic decrease, feedback system. VEGF: vascular endothelial growth factor; BDNF: brain-derived neurotrophic factor</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-110-01-0091-80002-gf01.jpg"/></fig>
    </p>
    <p>Thus, it can be observed that the damages caused in the cognitive aspects are often reversible and, therefore, possible to improve the executive functions,<xref ref-type="bibr" rid="B18">18</xref> increasing the quality of life of these patients. It is worth mentioning, then, that APA is a useful tool as part of the treatment of these patients, besides being a non-pharmacological alternative and low cost. Although APA is easy to perform in healthy subjects, the same cannot be said for patients with HF. FC IV patients, for example, are not advised to perform physical activity. In addition, some procedures should be done before the practice, such as performing the maximum effort test for physical and clinical condition analysis. The prescription should be made based on evaluations performed periodically by the cardiologist and on the risk stratification of the patient and the practice should not be performed without supervision.<xref ref-type="bibr" rid="B2">2</xref>
		</p>
    <p>Therefore, the importance of physical activity in a much broader context that goes beyond the improvement of the heart, which is the benefit of the brain function of patients with heart failure, through functional and morphological changes in the brain and ANS, is clear, implying greater efficiency in cognitive processes. Therefore, it is valid to emphasize once again the prescription of APA with a focus on cognition, with the justification of enhancing performance in the basic and instrumental activities of this population and explaining its practical benefits and its contribution to the possibility of greater well-being of the patients during the evolution of the clinical condition.</p>
    <p>Finally, in addition to combating sedentary lifestyle and improved heart muscle, APA prescription should be focused on cognitive benefit, with repercussion in the management of possible daily limitations, such as shopping, compromising understanding, communication and interpersonal relationships. This can be a way to increase the patient's adherence to this therapeutic component, aiding in his treatment and bringing more benefits and quality of life.</p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This study is not associated with any thesis or dissertation work.</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>References</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1 Bocchi EA. Heart failure in South America. Curr Cardiol Rev. 2013;9(2):147-56. PMID: 23597301.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bocchi</surname>
              <given-names>EA</given-names>
            </name>
          </person-group>
          <article-title>Heart failure in South America</article-title>
          <source>Curr Cardiol Rev</source>
          <year>2013</year>
          <volume>9</volume>
          <issue>2</issue>
          <fpage>147</fpage>
          <lpage>156</lpage>
          <pub-id pub-id-type="pmid">23597301</pub-id>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2 Bocchi EA, Marcondes-Braga FG, Ayub Ferreira SM, Rohde LE, Oliveira WA, Almeida DR, et al; Sociedade Brasileira de Cardiologia. [III Brazilian guidelines on chronic heart failure]. Arq Bras Cardiol. 2009;93(1 Suppl.1):3-70. PMID: 20963312.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bocchi</surname>
              <given-names>EA</given-names>
            </name>
            <name>
              <surname>Marcondes-Braga</surname>
              <given-names>FG</given-names>
            </name>
            <name>
              <surname>Ayub Ferreira</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Rohde</surname>
              <given-names>LE</given-names>
            </name>
            <name>
              <surname>Oliveira</surname>
              <given-names>WA</given-names>
            </name>
            <name>
              <surname>Almeida</surname>
              <given-names>DR</given-names>
            </name>
            <etal/>
            <collab>Sociedade Brasileira de Cardiologia</collab>
          </person-group>
          <article-title>[III Brazilian guidelines on chronic heart failure]</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2009</year>
          <volume>93</volume>
          <issue>1</issue>
          <supplement>Suppl.1</supplement>
          <fpage>3</fpage>
          <lpage>70</lpage>
          <pub-id pub-id-type="pmid">20963312</pub-id>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3 Vogels RL, Scheltens P, Schroeder-Tanka JM, Weinstein HC. Cognitive impairment in heart failure: a systematic review of the literature. Eur J Heart Fail. 2007;9(5):440-9. doi: 10.1016/j.ejheart.2006.11.001.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Vogels</surname>
              <given-names>RL</given-names>
            </name>
            <name>
              <surname>Scheltens</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Schroeder-Tanka</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Weinstein</surname>
              <given-names>HC</given-names>
            </name>
          </person-group>
          <article-title>Cognitive impairment in heart failure: a systematic review of the literature</article-title>
          <source>Eur J Heart Fail</source>
          <year>2007</year>
          <volume>9</volume>
          <issue>5</issue>
          <fpage>440</fpage>
          <lpage>449</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ejheart.2006.11.001</pub-id>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4 Diamond A. Executive functions. Annu Rev Psychol. 2013;64:135-68. doi: 10.1146/annurev-psych-113011-143750.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Diamond</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Executive functions</article-title>
          <source>Annu Rev Psychol</source>
          <year>2013</year>
          <volume>64</volume>
          <fpage>135</fpage>
          <lpage>168</lpage>
          <pub-id pub-id-type="doi">10.1146/annurev-psych-113011-143750</pub-id>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5 Woo MA, Kumar R, Macey PM, Fonarow GC, Harper RM. Brain injury in autonomic, emotional, and cognitive regulatory areas in patients with heart failure. J Card Fail. 2009;15(3):214-23. doi: 10.1016/j.cardfail.2008.10.020.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Woo</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Kumar</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Macey</surname>
              <given-names>PM</given-names>
            </name>
            <name>
              <surname>Fonarow</surname>
              <given-names>GC</given-names>
            </name>
            <name>
              <surname>Harper</surname>
              <given-names>RM</given-names>
            </name>
          </person-group>
          <article-title>Brain injury in autonomic, emotional, and cognitive regulatory areas in patients with heart failure</article-title>
          <source>J Card Fail</source>
          <year>2009</year>
          <volume>15</volume>
          <issue>3</issue>
          <fpage>214</fpage>
          <lpage>223</lpage>
          <pub-id pub-id-type="doi">10.1016/j.cardfail.2008.10.020</pub-id>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6 Alagiakrishnan K, Mah D, Ahmed A, Ezekowitz J. Cognitive decline in heart failure. Heart Fail Rev. 2016;21(6):661-73. doi: 10.1007/s10741-016-9568-1.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Alagiakrishnan</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Mah</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Ahmed</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Ezekowitz</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Cognitive decline in heart failure</article-title>
          <source>Heart Fail Rev</source>
          <year>2016</year>
          <volume>21</volume>
          <issue>6</issue>
          <fpage>661</fpage>
          <lpage>673</lpage>
          <pub-id pub-id-type="doi">10.1007/s10741-016-9568-1</pub-id>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7 Nolan J, Batin PD, Andrews R, Lindsay SJ, Brooksby P, Mullen M, et al. Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation. 1998;98(15):1510-6. PMID: 9769304.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nolan</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Batin</surname>
              <given-names>PD</given-names>
            </name>
            <name>
              <surname>Andrews</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Lindsay</surname>
              <given-names>SJ</given-names>
            </name>
            <name>
              <surname>Brooksby</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Mullen</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart)</article-title>
          <source>Circulation</source>
          <year>1998</year>
          <volume>98</volume>
          <issue>15</issue>
          <fpage>1510</fpage>
          <lpage>1516</lpage>
          <pub-id pub-id-type="pmid">9769304</pub-id>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8 Creager MA, Faxon DP, Cutler SS, Kohlmann O, Ryan TJ, Gavras H. Contribution of vasopressin to vasoconstriction in patients with congestive heart failure: comparison with the renin-angiotensin system and the sympathetic nervous system. J Am Coll Cardiol. 1986;7(4):758-65. PMID: 3514728.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Creager</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Faxon</surname>
              <given-names>DP</given-names>
            </name>
            <name>
              <surname>Cutler</surname>
              <given-names>SS</given-names>
            </name>
            <name>
              <surname>Kohlmann</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Ryan</surname>
              <given-names>TJ</given-names>
            </name>
            <name>
              <surname>Gavras</surname>
              <given-names>H</given-names>
            </name>
          </person-group>
          <article-title>Contribution of vasopressin to vasoconstriction in patients with congestive heart failure: comparison with the renin-angiotensin system and the sympathetic nervous system</article-title>
          <source>J Am Coll Cardiol</source>
          <year>1986</year>
          <volume>7</volume>
          <issue>4</issue>
          <fpage>758</fpage>
          <lpage>765</lpage>
          <pub-id pub-id-type="pmid">3514728</pub-id>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9 Fraser KS, Heckman GA, McKelvie RS, Harkness K, Middleton LE, Hughson RL. Cerebral hypoperfusion is exaggerated with an upright posture in heart failure: impact of depressed cardiac output. JACC Heart Fail. 2015;3(2):168-75. doi: 10.1016/j.jchf.2014.07.017.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fraser</surname>
              <given-names>KS</given-names>
            </name>
            <name>
              <surname>Heckman</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>McKelvie</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Harkness</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Middleton</surname>
              <given-names>LE</given-names>
            </name>
            <name>
              <surname>Hughson</surname>
              <given-names>RL</given-names>
            </name>
          </person-group>
          <article-title>Cerebral hypoperfusion is exaggerated with an upright posture in heart failure: impact of depressed cardiac output</article-title>
          <source>JACC Heart Fail</source>
          <year>2015</year>
          <volume>3</volume>
          <issue>2</issue>
          <fpage>168</fpage>
          <lpage>175</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jchf.2014.07.017</pub-id>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10 van Praag H. Neurogenesis and exercise: past and future directions. Neuromolecular Med. 2008;10(2):128-40. doi: 10.1007/s12017-008-8028-z.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>van Praag</surname>
              <given-names>H</given-names>
            </name>
          </person-group>
          <article-title>Neurogenesis and exercise: past and future directions</article-title>
          <source>Neuromolecular Med</source>
          <year>2008</year>
          <volume>10</volume>
          <issue>2</issue>
          <fpage>128</fpage>
          <lpage>140</lpage>
          <pub-id pub-id-type="doi">10.1007/s12017-008-8028-z</pub-id>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11 Gelow JM, Mudd JO, Chien CV, Lee CS. Usefulness of cognitive dysfunction in heart failure to predict cardiovascular risk at 180 days. Am J Cardiol. 2015;115(6):778-82. doi: 10.1016/j.amjcard.2014.12.040.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gelow</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Mudd</surname>
              <given-names>JO</given-names>
            </name>
            <name>
              <surname>Chien</surname>
              <given-names>CV</given-names>
            </name>
            <name>
              <surname>Lee</surname>
              <given-names>CS</given-names>
            </name>
          </person-group>
          <article-title>Usefulness of cognitive dysfunction in heart failure to predict cardiovascular risk at 180 days</article-title>
          <source>Am J Cardiol</source>
          <year>2015</year>
          <volume>115</volume>
          <issue>6</issue>
          <fpage>778</fpage>
          <lpage>782</lpage>
          <pub-id pub-id-type="doi">10.1016/j.amjcard.2014.12.040</pub-id>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12 Fu Q, Levine BD. Exercise and the autonomic nervous system. Handb Clin Neurol. 2013;117:147-60. doi: 10.1016/B978-0-444-53491-0.00013-4.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fu</surname>
              <given-names>Q</given-names>
            </name>
            <name>
              <surname>Levine</surname>
              <given-names>BD</given-names>
            </name>
          </person-group>
          <article-title>Exercise and the autonomic nervous system</article-title>
          <source>Handb Clin Neurol</source>
          <year>2013</year>
          <volume>117</volume>
          <fpage>147</fpage>
          <lpage>160</lpage>
          <pub-id pub-id-type="doi">10.1016/B978-0-444-53491-0.00013-4</pub-id>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>13 Tempest GD, Davranche K, Brisswalter J, Perrey S, Radel R. The differential effects of prolonged exercise upon executive function and cerebral oxygenation. Brain Cogn. 2017 Apr;113:133-41. doi: 10.1016/j.bandc.2017.02.001.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tempest</surname>
              <given-names>GD</given-names>
            </name>
            <name>
              <surname>Davranche</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Brisswalter</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Perrey</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Radel</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <article-title>The differential effects of prolonged exercise upon executive function and cerebral oxygenation</article-title>
          <source>Brain Cogn</source>
          <year>2017</year>
          <month>04</month>
          <volume>113</volume>
          <fpage>133</fpage>
          <lpage>141</lpage>
          <pub-id pub-id-type="doi">10.1016/j.bandc.2017.02.001</pub-id>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>14 Hillman CH, Erickson KI, Kramer AF. Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci. 2008;9(1):58-65. doi: 10.1038/nrn2298.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hillman</surname>
              <given-names>CH</given-names>
            </name>
            <name>
              <surname>Erickson</surname>
              <given-names>KI</given-names>
            </name>
            <name>
              <surname>Kramer</surname>
              <given-names>AF</given-names>
            </name>
          </person-group>
          <article-title>Be smart, exercise your heart: exercise effects on brain and cognition</article-title>
          <source>Nat Rev Neurosci</source>
          <year>2008</year>
          <volume>9</volume>
          <issue>1</issue>
          <fpage>58</fpage>
          <lpage>65</lpage>
          <pub-id pub-id-type="doi">10.1038/nrn2298</pub-id>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>15 Swain RA, Harris AB, Wiener EC, Dutka MV, Morris HD, Theien BE, et al. Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat. Neuroscience. 2003;117(4):1037-46. PMID: 12654355.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Swain</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Harris</surname>
              <given-names>AB</given-names>
            </name>
            <name>
              <surname>Wiener</surname>
              <given-names>EC</given-names>
            </name>
            <name>
              <surname>Dutka</surname>
              <given-names>MV</given-names>
            </name>
            <name>
              <surname>Morris</surname>
              <given-names>HD</given-names>
            </name>
            <name>
              <surname>Theien</surname>
              <given-names>BE</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat</article-title>
          <source>Neuroscience</source>
          <year>2003</year>
          <volume>117</volume>
          <issue>4</issue>
          <fpage>1037</fpage>
          <lpage>1046</lpage>
          <pub-id pub-id-type="pmid">12654355</pub-id>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>16 Tanne D, Freimark D, Poreh A, Merzeliak O, Bruck B, Schwammenthal Y, et al. Cognitive functions in severe congestive heart failure before and after an exercise training program. Int J Cardiol. 2005;103(2):145-9. doi: 10.1016/j.ijcard.2004.08.044.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tanne</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Freimark</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Poreh</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Merzeliak</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Bruck</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Schwammenthal</surname>
              <given-names>Y</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Cognitive functions in severe congestive heart failure before and after an exercise training program</article-title>
          <source>Int J Cardiol</source>
          <year>2005</year>
          <volume>103</volume>
          <issue>2</issue>
          <fpage>145</fpage>
          <lpage>149</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ijcard.2004.08.044</pub-id>
        </element-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <mixed-citation>17 Baldasseroni S, Mossello E, Romboli B, Orso F, Colombi C, Fumagalli S, et al. Relationship between cognitive function and 6-minute walking test in older outpatients with chronic heart failure. Aging Clin Exp Res. 2010;22(4):308-13. PMID: 21116123.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Baldasseroni</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Mossello</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Romboli</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Orso</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Colombi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Fumagalli</surname>
              <given-names>S</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Relationship between cognitive function and 6-minute walking test in older outpatients with chronic heart failure</article-title>
          <source>Aging Clin Exp Res</source>
          <year>2010</year>
          <volume>22</volume>
          <issue>4</issue>
          <fpage>308</fpage>
          <lpage>313</lpage>
          <pub-id pub-id-type="pmid">21116123</pub-id>
        </element-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <mixed-citation>18 Galioto R, Fedor AF, Gunstad J. Possible neurocognitive benefits of exercise in persons with heart failure. Eur Rev Aging Phys Act. 2015 Oct 23;12:6. doi: 10.1186/s11556-015-0151-x.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Galioto</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Fedor</surname>
              <given-names>AF</given-names>
            </name>
            <name>
              <surname>Gunstad</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Possible neurocognitive benefits of exercise in persons with heart failure</article-title>
          <source>Eur Rev Aging Phys Act</source>
          <year>2015</year>
          <month>10</month>
          <day>23</day>
          <volume>12</volume>
          <fpage>6</fpage>
          <lpage>6</lpage>
          <pub-id pub-id-type="doi">10.1186/s11556-015-0151-x</pub-id>
        </element-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <mixed-citation>19 Besnier F, Labrun&#233;e M, Pathak A, Pavy-Le Traon A, Gal&#232;s C, S&#233;nard JM, et al. Exercise training-induced modification in autonomic nervous system: An update for cardiac patients. Ann Phys Rehabil Med. 2017;60(1):27-35. doi: 10.1016/j.rehab.2016.07.002.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Besnier</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Labrun&#233;e</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Pathak</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Pavy-Le Traon</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Gal&#232;s</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>S&#233;nard</surname>
              <given-names>JM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Exercise training-induced modification in autonomic nervous system: An update for cardiac patients</article-title>
          <source>Ann Phys Rehabil Med</source>
          <year>2017</year>
          <volume>60</volume>
          <issue>1</issue>
          <fpage>27</fpage>
          <lpage>35</lpage>
          <pub-id pub-id-type="doi">10.1016/j.rehab.2016.07.002</pub-id>
        </element-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <mixed-citation>20 Thayer JF, Lane RD. Claude Bernard and the heart-brain connection: further elaboration of a model of neurovisceral integration. Neurosci Biobehav Rev. 2009;33(2):81-8. doi: 10.1016/j.neubiorev.2008.08.004.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Thayer</surname>
              <given-names>JF</given-names>
            </name>
            <name>
              <surname>Lane</surname>
              <given-names>RD</given-names>
            </name>
          </person-group>
          <article-title>Claude Bernard and the heart-brain connection: further elaboration of a model of neurovisceral integration</article-title>
          <source>Neurosci Biobehav Rev</source>
          <year>2009</year>
          <volume>33</volume>
          <issue>2</issue>
          <fpage>81</fpage>
          <lpage>88</lpage>
          <pub-id pub-id-type="doi">10.1016/j.neubiorev.2008.08.004</pub-id>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Ponto de vista</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>D&#233;ficit Cognitivo na Insufici&#234;ncia Card&#237;aca e os Benef&#237;cios da Atividade F&#237;sica Aer&#243;bia</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>R&#234;go</surname>
            <given-names>Maria Lu&#237;za de Medeiros</given-names>
          </name>
          <xref ref-type="aff" rid="aff3"/>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cabral</surname>
            <given-names>Daniel Aranha Rego</given-names>
          </name>
          <xref ref-type="aff" rid="aff3"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fontes</surname>
            <given-names>Eduardo Bodnariuc</given-names>
          </name>
          <xref ref-type="aff" rid="aff3"/>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
      </contrib-group>
      <aff id="aff3">
        <institution content-type="original">Universidade Federal do Rio Grande do Norte (UFRN); NeuroEx, Natal, RN &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Maria Lu&#237;za de Medeiros R&#234;go,</bold> Rua Raimundo Chaves, 1652, F5. CEP 59064-390, Candel&#225;ria, Natal, RN - Brasil. E-mail: <email>marialuizamedeirosr@gmail.com</email>, <email>eduardobfontes@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa, Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: R&#234;go MLM, Cabral DAR, Fontes EB.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <p>A Insufici&#234;ncia Card&#237;aca &#233; uma s&#237;ndrome cl&#237;nica prevalente em todo o mundo e de grande contribui&#231;&#227;o para a morbimortalidade de cardiopatas no Brasil. Al&#233;m disso, tal patologia &#233; fortemente relacionada &#224; disfun&#231;&#227;o cerebral, sendo constatada alta preval&#234;ncia de comprometimento cognitivo. Muitos mecanismos podem ser relacionados &#224; perda cognitiva, como hipoperfus&#227;o cerebral, atrofia e perda de massa cinzenta do c&#233;rebro e, ainda, disfun&#231;&#227;o do sistema nervoso aut&#244;nomo. A literatura &#233; clara quanto aos benef&#237;cios da atividade f&#237;sica aer&#243;bia em popula&#231;&#245;es saud&#225;veis na modula&#231;&#227;o do sistema nervoso aut&#244;nomo e nas fun&#231;&#245;es cerebrais. Na popula&#231;&#227;o de insuficientes card&#237;acos, estudos demonstram que o exerc&#237;cio &#233; associado &#224; melhora na fun&#231;&#227;o cognitiva, assim como na regula&#231;&#227;o auton&#244;mica card&#237;aca. Entretanto, pouca &#234;nfase foi dada aos mecanismos pelos quais a atividade f&#237;sica aer&#243;bia pode beneficiar o funcionamento cerebral, o sistema nervoso aut&#244;nomo e repercutir em um melhor desempenho cognitivo, particularmente em pacientes com insufici&#234;ncia card&#237;aca. Dessa forma, o presente trabalho apresenta as vias pelas quais &#225;reas cerebrais respons&#225;veis pela cogni&#231;&#227;o atuam tamb&#233;m na modula&#231;&#227;o do sistema nervoso aut&#244;nomo, e ressalta sua import&#226;ncia para o entendimento do comprometimento cognitivo frente &#224; fisiopatologia da insufici&#234;ncia card&#237;aca. &#201; descrito ainda o modo pelo qual a atividade f&#237;sica aer&#243;bia pode promover benef&#237;cios quando integrado &#224; terap&#234;utica, associada a um melhor progn&#243;stico do quadro cl&#237;nico desses pacientes.</p>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Insufici&#234;ncia Card&#237;aca</kwd>
        <kwd>Indicadores de Morbimortalidade</kwd>
        <kwd>Cogni&#231;&#227;o</kwd>
        <kwd>Exerc&#237;cio</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>A insufici&#234;ncia Card&#237;aca (IC) &#233; respons&#225;vel por cerca de 50% de todas as interna&#231;&#245;es hospitalares que ocorrem na Am&#233;rica do Sul<xref ref-type="bibr" rid="B1">1</xref> e &#233; uma das causas mais frequente de hospitaliza&#231;&#227;o por doen&#231;as cardiovasculares.<xref ref-type="bibr" rid="B2">2</xref> Al&#233;m da direta influ&#234;ncia no controle auton&#244;mico card&#237;aco, a IC &#233; fortemente relacionada &#224; presen&#231;a de disfun&#231;&#227;o cerebral e comprometimento cognitivo, acometendo cerca de 75% dessa popula&#231;&#227;o.<xref ref-type="bibr" rid="B3">3</xref> Esse d&#233;ficit cognitivo est&#225; associado &#224;s fun&#231;&#245;es executivas, incluindo dificuldades no planejamento e execu&#231;&#227;o das a&#231;&#245;es, baixa capacidade de resolu&#231;&#227;o de problemas e de inibi&#231;&#227;o de comportamentos.<xref ref-type="bibr" rid="B4">4</xref> Na pr&#225;tica, isso &#233; traduzido como menor capacidade de realizar atividades do cotidiano como compras, alimenta&#231;&#227;o e locomo&#231;&#227;o - incluindo a deambula&#231;&#227;o - al&#233;m de relacionar-se com menores n&#237;veis de autocuidado, maiores &#237;ndices de hospitaliza&#231;&#245;es, aumento de gastos com as mais frequentes entradas nos hospitais e, por fim, h&#225; um aumento da morbimortalidade nessa patologia. Nesse sentido, diversos tratamentos s&#227;o realizados com intuito de amenizar os efeitos delet&#233;rios causados pela IC. Contudo, esses tratamentos, quase sempre envolvem procedimentos invasivos e/ou medicamentosos como transplante de cora&#231;&#227;o, dispositivo de assist&#234;ncia do ventr&#237;culo esquerdo, betabloqueadores, antagonistas de aldosterona e inibidores da enzima conversora de angiotensina. Todos esses f&#225;rmacos, apesar de terem resultados ben&#233;ficos comprovados, podem desenvolver diversos tipos de efeitos colaterais como insufici&#234;ncia renal e hiperpotassemia.<xref ref-type="bibr" rid="B2">2</xref> Nesse sentido, o exerc&#237;cio f&#237;sico tem sido apontado como uma importante ferramenta auxiliar no tratamento de pacientes com IC, no entanto, pouco tem sido tratado sobre seus benef&#237;cios &#224; fun&#231;&#227;o cerebral. No presente trabalho, s&#227;o apresentadas as vias pelas quais o c&#243;rtex pr&#233;-frontal (CPF) est&#225; intimamente ligado &#224; regula&#231;&#227;o do controle auton&#244;mico card&#237;aco e ressalta sua influ&#234;ncia sobre o comprometimento cognitivo em pacientes com IC. Al&#233;m disso, &#233; descrito como a pr&#225;tica regular de atividade f&#237;sica pode promover benef&#237;cios &#224; fun&#231;&#227;o cerebral e desempenho cognitivo nessa popula&#231;&#227;o, al&#233;m da contribui&#231;&#227;o sobre o controle auton&#244;mico card&#237;aco j&#225; amplamente descrito.</p>
      <p>Buscando a g&#234;nese desse problema, muitos mecanismos podem ser relacionados &#224; perda cognitiva, como hipoperfus&#227;o cerebral, atrofia e perda de massa cinzenta do c&#233;rebro, bem como disfun&#231;&#227;o do sistema nervoso aut&#244;nomo (SNA).<xref ref-type="bibr" rid="B5">5</xref> Um estudo com neuroimagem em pacientes CF II constatou que os indiv&#237;duos portadores dessa s&#237;ndrome tinham preju&#237;zo em diversas &#225;reas cerebrais como o hipocampo(convers&#227;o de mem&#243;ria de curto prazo em mem&#243;ria de longo prazo), n&#250;cleo caudado (modula&#231;&#227;o de movimentos corporais), CPF (fun&#231;&#245;es executivas: tomada de decis&#227;o, planejamento, controle inibit&#243;rio) e hipot&#225;lamo, &#225;reas fundamentais em processos cognitivos e controle auton&#244;mico.<xref ref-type="bibr" rid="B5">5</xref> Nessa perspectiva, vale ressaltar a exist&#234;ncia de um recente modelo fisiopatol&#243;gico do decl&#237;nio cognitivo nessa popula&#231;&#227;o, o qual afirma que um conjunto de fatores como hipoperfus&#227;o, hip&#243;xia, aumento de citocinas inflamat&#243;rias, doen&#231;as tromboemb&#243;licas e anormalidades hemodin&#226;micas podem levar &#224; atrofia de massa cerebral, gerando d&#233;ficits cognitivos.<xref ref-type="bibr" rid="B6">6</xref> Outro ponto importante a ser ressaltado sobre a fisiopatologia imposta pela IC &#233; a severa disfun&#231;&#227;o no SNA, caracterizada pelo aumento do t&#244;nus simp&#225;tico e diminui&#231;&#227;o do parassimp&#225;tico<xref ref-type="bibr" rid="B7">7</xref> podendo estar relacionada &#224; vasoconstri&#231;&#227;o.<xref ref-type="bibr" rid="B8">8</xref> Como consequ&#234;ncia desse balan&#231;o auton&#244;mico com sobreposi&#231;&#227;o simp&#225;tica, h&#225; dificuldade para a chegada de sangue em diversos sistemas do corpo, incluindo o c&#233;rebro. A hipoperfus&#227;o cerebral em pacientes com IC pode levar &#224; redu&#231;&#227;o da capacidade funcional<xref ref-type="bibr" rid="B9">9</xref> e d&#233;ficits cognitivos.<xref ref-type="bibr" rid="B5">5</xref> Mais especificamente, o comprometimento permanente da perfus&#227;o cerebral e isquemia cr&#244;nica em &#225;reas profundas podem resultar em dano cognitivo e dificuldade na execu&#231;&#227;o de atividades rotineiras. O hipocampo, por exemplo, possui plasticidade neural frente &#224; menor oferta de oxig&#234;nio e pode ter sua massa diminu&#237;da e, possivelmente, causar preju&#237;zos de mem&#243;ria.<xref ref-type="bibr" rid="B10">10</xref>
			</p>
      <p>Tem sido demonstrado que pacientes CF I-III possuem baixo fluxo sangu&#237;neo cerebral (FSC) na posi&#231;&#227;o sentada e isso est&#225; relacionado com baixo d&#233;bito card&#237;aco, podendo causar intensa hipoperfus&#227;o na realiza&#231;&#227;o de tarefas simples, como o ato de sair de uma posi&#231;&#227;o deitada para uma sentada.<xref ref-type="bibr" rid="B9">9</xref> Logo, com menor oferta de oxig&#234;nio ao c&#233;rebro, os preju&#237;zos cognitivos s&#227;o praticamente inevit&#225;veis. Al&#233;m disso, j&#225; foi observado que o grau da disfun&#231;&#227;o cognitiva pode servir como preditor de complica&#231;&#245;es cardiovasculares em pacientes com IC. No estudo, 246 pacientes CF II - IV realizaram o <italic>Montreal Cognitive Assessment</italic> para avaliar a capacidade cognitiva e foi demonstrado que o pior desempenho no teste foi daqueles com maiores chances de eventos cardiovasculares em at&#233; 180 dias.<xref ref-type="bibr" rid="B11">11</xref> Desse modo, a cogni&#231;&#227;o parece estar intimamente relacionada ao grau de oxigena&#231;&#227;o cerebral e, quanto mais hipoperfundido for o c&#233;rebro, maior ser&#225; a disfun&#231;&#227;o do sistema nervoso, indicando maior preju&#237;zo no d&#233;bito card&#237;aco e menor capacidade em modular a atividade auton&#244;mica, aumentando o risco de eventos cardio e cerebrovasculares.</p>
      <p>Dito isso, a literatura &#233; clara quanto aos benef&#237;cios da atividade f&#237;sica aer&#243;bia (AFA), em popula&#231;&#245;es saud&#225;veis, na modula&#231;&#227;o do SNA e nas fun&#231;&#245;es cerebrais e cognitivas. Evid&#234;ncias mostram que a AFA realizada cronicamente, tem a capacidade de promover efeitos ben&#233;ficos na sa&#250;de cardiovascular, mediados pelo aumento do t&#244;nus vagal e diminui&#231;&#227;o da atividade simp&#225;tica no nodo sinusal, com melhora da fun&#231;&#227;o vascular, remodelamento card&#237;aco e fun&#231;&#245;es renais-adrenais.<xref ref-type="bibr" rid="B12">12</xref> No entanto, a AFA regular tamb&#233;m tem demonstrado papel importante na modula&#231;&#227;o de algumas regi&#245;es cerebrais de fundamental import&#226;ncia nos processos cognitivos, atrav&#233;s do aumento do FSC, no CPF,<xref ref-type="bibr" rid="B13">13</xref> do aumento do volume no hipocampo,<xref ref-type="bibr" rid="B10">10</xref> do aumento das concentra&#231;&#245;es de fatores de crescimento endotelial vascular (VEGF) (crescimento de novos capilares) e de fator neurotr&#243;fico derivado do c&#233;rebro (BDNF) (fortalecimento de conex&#245;es sin&#225;pticas),<xref ref-type="bibr" rid="B14">14</xref> bem como angiog&#234;nese em regi&#245;es do lobofrontal.<xref ref-type="bibr" rid="B15">15</xref> Logo, essas mudan&#231;as funcionais, bioqu&#237;micas e morfol&#243;gicas do c&#233;rebro est&#227;o fortemente ligadas &#224; melhora cognitiva.</p>
      <p>Seguindo essa linha de racioc&#237;nio, em um estudo com pacientes CF III e fra&#231;&#227;o de eje&#231;&#227;o &#8804; 35%, foi realizada uma interven&#231;&#227;o de 18 semanas (duas vezes por semana) de exerc&#237;cios f&#237;sicos que alternavam entre esteira, cicloerg&#244;metro e simulador de escada. Os resultados demonstraram que o exerc&#237;cio aprimorou as fun&#231;&#245;es cognitivas de aten&#231;&#227;o seletiva e velocidade psicomotora.<xref ref-type="bibr" rid="B16">16</xref> Al&#233;m disso, o desempenho do teste de caminhada de seis minutos e a pontua&#231;&#227;o no Mini Exame do Estado Mental tem sido diretamente correlacionados, indicando que quanto menor a capacidade cardiovascular funcional do sujeito, menor sua capacidade cognitiva.<xref ref-type="bibr" rid="B17">17</xref> Nesse &#237;nterim, &#233; v&#225;lido mencionar que comumente os pacientes saem dos consult&#243;rios m&#233;dicos tendo escutado que a pr&#225;tica de exerc&#237;cios f&#237;sicos &#233; importante para combater o sedentarismo, melhorar a fun&#231;&#227;o do m&#250;sculo card&#237;aco e, portanto, tornarem-se mais saud&#225;veis e com melhor qualidade de vida. Entretanto, &#233; preocupante a pouca &#234;nfase dada aos benef&#237;cios cognitivos e a melhoria na fun&#231;&#227;o cerebral que a atividade f&#237;sica pode proporcionar aos portadores de IC.</p>
      <p>Nesse contexto, uma recente revis&#227;o aborda a pr&#225;tica da AFA como um fator ben&#233;fico por prevenir e at&#233; reverter os preju&#237;zos cognitivos causados principalmente pela diminui&#231;&#227;o do FSC nessa popula&#231;&#227;o. Esse benef&#237;cio seria consequ&#234;ncia tanto da melhora na atividade contr&#225;til muscular card&#237;aca, quanto da diminui&#231;&#227;o da resist&#234;ncia vascular perif&#233;rica por uma diminui&#231;&#227;o da ativa&#231;&#227;o simp&#225;tica.<xref ref-type="bibr" rid="B18">18</xref> Ainda, j&#225; foram demonstrados os poss&#237;veis efeitos da AFA no SNA de pacientes com doen&#231;as card&#237;acas como no caso da IC, indicando a poss&#237;vel modula&#231;&#227;o simpatovagal com aumento do t&#244;nus parassimp&#225;tico e diminui&#231;&#227;o da atividade simp&#225;tica, a qual constitui um quadro extremamente importante e decisivo para essa popula&#231;&#227;o.<xref ref-type="bibr" rid="B19">19</xref> Contudo, pouco destaque foi dado a integra&#231;&#227;o entre o FSC e o sistema nervoso aut&#244;nomo, bem como na modula&#231;&#227;o do SNA em decorr&#234;ncia da realiza&#231;&#227;o do exerc&#237;cio em pacientes com IC. Al&#233;m das poss&#237;veis vias de integra&#231;&#227;o decorrentes dessa modula&#231;&#227;o do SNA e da sua influ&#234;ncia na atividade do SNC de modo geral, implicando maiores benef&#237;cios para o indiv&#237;duo.</p>
      <p>As vias pelas quais regi&#245;es frontais, como o CPF, atuam na modula&#231;&#227;o do SNA s&#227;o importantes para o entendimento da fisiopatologia da IC, bem como para entender como o AFA pode interferir nesses dois aspectos (cogni&#231;&#227;o e controle auton&#244;mico card&#237;aco). Nesse sentido, foi proposto um modelo neurovisceral pelo qual o CPF tem fun&#231;&#227;o inibit&#243;ria sobre a am&#237;gdala<xref ref-type="bibr" rid="B20">20</xref> (&#225;rea integrativa que recebe afer&#234;ncias sensoriais, confere cunho emocional e emite efer&#234;ncias para &#225;reas corticais). Entretanto, quando essa regi&#227;o est&#225; desinibida, situa&#231;&#227;o que pode ocorrer devido ao menor FSC no CPF, permite a ativa&#231;&#227;o de neur&#244;nios simp&#225;ticos e diminui&#231;&#227;o da a&#231;&#227;o de neur&#244;nios parassimp&#225;ticos, ambos no tronco cerebral,<xref ref-type="bibr" rid="B20">20</xref> desencadeando um balan&#231;o auton&#244;mico nervoso com predom&#237;nio simp&#225;tico. Sabe-se que a AFA tem papel atuante, especialmente no CPF<xref ref-type="bibr" rid="B13">13</xref> e na modula&#231;&#227;o auton&#244;mica,<xref ref-type="bibr" rid="B12">12</xref> criando um sistema que se retroalimenta, no qual a AFA atua em v&#225;rias esferas, culminando com a melhora cognitiva dos pacientes (<xref ref-type="fig" rid="f2">Figura 1</xref>) e, consequentemente, melhorando o progn&#243;stico.</p>
      <p>
        <fig id="f2">
          <label>Figura 1</label>
          <caption>
            <title>Atividade f&#237;sica aer&#243;bia promove aumento nas concentra&#231;&#245;es de VEGF e BDNF podendo melhorar processos cognitivos e aumentar o t&#244;nus parassimp&#225;tico e diminuir a ativa&#231;&#227;o simp&#225;tica. Essa condi&#231;&#227;o pode diminuir a resist&#234;ncia vascular perif&#233;rica e levar ao aumento do fluxo sangu&#237;neo cerebral no c&#243;rtex pr&#233;-frontal, interferindo positivamente na capacidade cognitiva. Com o aumento do fluxo sangu&#237;neo cerebral no c&#243;rtex pr&#233;-frontal, pode haver uma inibi&#231;&#227;o da am&#237;gdala promovendo a um aumento vagal e diminui&#231;&#227;o simp&#225;tica, retroalimentado o sistema. VEGF: fator de crescimento endotelial vascular; BDNF: fator neurotr&#243;fico derivado do c&#233;rebro.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-110-01-0091-80002-gf01-pt.jpg"/></fig>
      </p>
      <p>Com isso, pode-se notar que os danos causados nos aspectos cognitivos s&#227;o, muitas vezes, revers&#237;veis e, portanto, poss&#237;veis de melhorar as fun&#231;&#245;es executivas<xref ref-type="bibr" rid="B18">18</xref> aumentando a qualidade de vida desses pacientes. Vale ressaltar, ent&#227;o, que a AFA &#233; uma ferramenta &#250;til como parte do tratamento desses pacientes, al&#233;m de ser uma alternativa n&#227;o farmacol&#243;gica e de baixo custo. Apesar de a AFA ser de f&#225;cil realiza&#231;&#227;o em sujeitos saud&#225;veis, n&#227;o se pode afirmar o mesmo para os portadores de IC. Pacientes CF IV, por exemplo, n&#227;o s&#227;o aconselhados a realizar atividade f&#237;sica. Al&#233;m disso, alguns procedimentos devem ser feitos antes da pr&#225;tica, como a realiza&#231;&#227;o do teste de esfor&#231;o m&#225;ximo para an&#225;lise da condi&#231;&#227;o f&#237;sica e cl&#237;nica. A prescri&#231;&#227;o deve ser feita com base em avalia&#231;&#245;es realizadas periodicamente pelo cardiologista e na estratifica&#231;&#227;o de risco do paciente e a pr&#225;tica n&#227;o deve ser realizada sem supervis&#227;o.<xref ref-type="bibr" rid="B2">2</xref>
			</p>
      <p>Logo, fica clara a import&#226;ncia da atividade f&#237;sica em um contexto bem mais amplo e que vai al&#233;m da melhora do cora&#231;&#227;o, que &#233; o benef&#237;cio da fun&#231;&#227;o cerebral de insuficientes card&#237;acos, atrav&#233;s de mudan&#231;as funcionais e morfol&#243;gicas no c&#233;rebro e SNA, implicando maior efici&#234;ncia em processos cognitivos. Portanto, &#233; v&#225;lido enfatizar mais uma vez a prescri&#231;&#227;o da AFA com foco tamb&#233;m na cogni&#231;&#227;o, com a justificativa de potencializar o desempenho nas atividades b&#225;sicas e instrumentais dessa popula&#231;&#227;o e explicitando seus benef&#237;cios pr&#225;ticos e a sua contribui&#231;&#227;o na possibilidade de um maior bem-estar dos pacientes durante a evolu&#231;&#227;o do quadro cl&#237;nico.</p>
      <p>Por fim, somada ao combate ao sedentarismo e &#224; melhora do m&#250;sculo card&#237;aco, a prescri&#231;&#227;o da AFA deve ser voltada ao benef&#237;cio cognitivo, com repercuss&#227;o no manejo de poss&#237;veis limita&#231;&#245;es cotidianas, como ir &#224;s compras, comprometimento da compreens&#227;o, comunica&#231;&#227;o e das rela&#231;&#245;es interpessoais. Essa pode ser uma forma de aumentar a ades&#227;o do paciente a esse componente terap&#234;utico, auxiliando o seu tratamento e trazendo mais benef&#237;cios e qualidade de vida.</p>
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    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
