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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">4LFY4TrMPztRLyVByr3TX9S</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2019000700009</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20190118</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Non-Pharmacological Treatment of Cardiovascular Disease | Importance of Physical Exercise</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Gomes</surname>
            <given-names>Mariana Janini</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pagan</surname>
            <given-names>Luana Urbano</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7728-4505</contrib-id>
          <name>
            <surname>Okoshi</surname>
            <given-names>Marina Politi</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Universidade Estadual Paulista</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina de Botucatu</institution>
          <addr-line>
            <city>Botucatu</city>
            <state>SP</state>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP - Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Marina Politi Okoshi &#8226;</bold> Departamento de Cl&#237;nica M&#233;dica. Rubi&#227;o J&#250;nior, S/N. Postal Code 18618-000, Rubi&#227;o J&#250;nior, Botucatu, SP - Brazil E-mail: <email>mpoliti@fmb.unesp.br</email>
				</corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>08</day>
        <month>08</month>
        <year>2019</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>07</month>
        <year>2019</year>
      </pub-date>
      <volume>113</volume>
      <issue>1</issue>
      <fpage>09</fpage>
      <lpage>10</lpage>
      <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>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Cardiovascular Diseases</kwd>
        <kwd>Heart Failure</kwd>
        <kwd>Exercise/prevention and control</kwd>
        <kwd>Physical Fitness</kwd>
        <kwd>Ventricular Remodeling</kwd>
        <kwd>Quality of Life</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>FAPESP</funding-source>
          <award-id>2014/21972-3</award-id>
          <award-id>2014/23592-3</award-id>
        </award-group>
        <award-group>
          <funding-source>CNPq</funding-source>
          <award-id>310876/2018-4</award-id>
          <award-id>153424/2018-4</award-id>
        </award-group>
      </funding-group>
    </article-meta>
  </front>
  <body>
    <p>Cardiovascular diseases are currently the major health problem and are directly involved in more than 17 million deaths each year, which represents 50% of all deaths from noncommunicable diseases.<xref ref-type="bibr" rid="B1">1</xref> In addition to their effects on individual well-being, cardiovascular diseases are responsible for a high economic impact. A recently published study showed that in Brazil, only four diseases - arterial hypertension, myocardial infarction, atrial fibrillation and heart failure - reached an estimated total financial cost of 56.2 billion reais in the year 2015.<xref ref-type="bibr" rid="B1">1</xref>
		</p>
    <p>The treatment of cardiovascular diseases involves the use of specific drugs and adherence to non-pharmacological interventions.<xref ref-type="bibr" rid="B2">2</xref> This Editorial will be dedicated to the role of physical exercise in the treatment of cardiovascular diseases.</p>
    <p>Brazil has a prominent position worldwide regarding the study of the effects of physical exercise in different clinical conditions. The practice of physical exercises has been recommended for decades for health promotion and treatment of several cardiovascular diseases. The regular practice of exercises results in several benefits, such as increased functional capacity and improved body composition, insulin resistance, endothelial function, arterial hypertension, antioxidant status, and quality of life.<xref ref-type="bibr" rid="B3">3</xref><sup>-</sup><xref ref-type="bibr" rid="B9">9</xref>
		</p>
    <p>Concerning heart failure, exercises have been recommended for almost three decades in the treatment of stable patients. In addition to increasing effort tolerance, it improves the quality of life and reduces hospitalizations for heart failure.<xref ref-type="bibr" rid="B2">2</xref> Despite a large number of studies evaluating the effects of exercise, its influence on different situations of cardiac aggression has yet to be fully clarified.<xref ref-type="bibr" rid="B10">10</xref>
		</p>
    <p>In articles recently published in this journal, the role of exercise and its molecular mechanisms of action have been evaluated in different heart disease experimental models.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref><sup>-</sup><xref ref-type="bibr" rid="B13">13</xref> The beneficial effects on cardiac remodeling have been frequently observed, such as attenuation of myocardial hypertrophy and left ventricular dysfunction.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> However, unexpected results have drawn attention to the need for better clarification of the subject. For instance, Rodrigues et al.<xref ref-type="bibr" rid="B13">13</xref> submitted beta-adrenergic receptor knockout mice, which may develop heart failure, to treadmill training for eight weeks. Surprisingly, the trained knockout animals showed a higher increase in functional capacity and myocardial contractility than the trained control animals. As an exaggerated contractility stimulus may lead to deterioration of cardiac function in the long-term, additional studies are required to define the role of exercise in cardiac function in beta-adrenergic receptor knockout mice in later life.</p>
    <p>Topics of great uncertainty regarding exercise prescription include the intensity and duration of exercise. Recently, Ellingsen et al.<xref ref-type="bibr" rid="B15">15</xref> published the first multicenter randomized trial comparing the effects of high-intensity interval training (HIIT) with those of continuous training at moderate intensity or recommendation for regular exercises in patients with heart failure with reduced ejection fraction. In both specific training groups, the results were only moderately better than the recommendation for regular exercise. Moreover, 51% of patients in the HIIT group exercised below the prescribed heart rate, and 80% of the individuals from continuous training group at moderate intensity trained at a frequency above their target. Thus, considering that HIIT was not superior to the continuous training group at moderate intensity in reducing the remodeling process or improving clinical outcomes, and the difficulty in attaining adherence to the prescribed intensity, the authors recommend that continuous training at moderate intensity should remain as the standard modality for patients with chronic heart failure.</p>
    <p>Another factor that remains to be clarified is whether the practice of exercise in short and intense periods repeated throughout the day, called accumulated exercise, can be an alternative for sedentary individuals. Martinez et al.<xref ref-type="bibr" rid="B16">16</xref> observed that both continuous and accumulated exercise improved the physical fitness of healthy rats. However, only the continuous exercise was able to reduce body weight gain and improve endothelial function. Aortas obtained from the group submitted to continuous exercise showed a reduction in the contractile response to norepinephrine and an increase in acetylcholine-induced relaxation, which was not observed in the group trained using accumulated exercise.<xref ref-type="bibr" rid="B16">16</xref>
		</p>
    <p>A greater consensus is observed in the literature regarding the role of physical exercise on the vascular system. Lemos et al.<xref ref-type="bibr" rid="B12">12</xref> showed that regular aerobic exercise for nine weeks led to the attenuation of sympathetic activity and reduction in vascular resistance, thus contributing to a decrease in blood pressure in spontaneously hypertensive rats. Resistance training was also effective in improving the bradycardic response and baroreflex sensitivity of spontaneously hypertensive rats.<xref ref-type="bibr" rid="B11">11</xref> However, the fact that these effects were not accompanied by a reduction in systemic blood pressure <xref ref-type="bibr" rid="B11">11</xref> suggests that aerobic exercise is superior to resistance training for arterial hypertension control.</p>
    <p>Despite the great advances regarding the understanding of physical exercise effects on the healthy cardiovascular system or that submitted to different types of aggression, we are still far from clarifying the physical exercise mechanisms of action and from scientifically defining the best prescription for patients with cardiovascular disease.</p>
  </body>
  <back>
    <ack>
      <title>Acknowledgements</title>
      <p>We would like to thank Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo - FAPESP (Proc. N. 2014/21972-3 and 2014/23592-3); Conselho Nacional de Desenvolvimento Cient&#237;fico e Tecnol&#243;gico - CNPq (Proc. N. 310876/2018-4 and 153424/2018-4).</p>
    </ack>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Tratamento N&#227;o Medicamentoso das Doen&#231;as Cardiovasculares | Import&#226;ncia do Exerc&#237;cio F&#237;sico</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Gomes</surname>
            <given-names>Mariana Janini</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">1</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pagan</surname>
            <given-names>Luana Urbano</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7728-4505</contrib-id>
          <name>
            <surname>Okoshi</surname>
            <given-names>Marina Politi</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">1</xref>
        </contrib>
        <aff id="aff2">
          <label>1</label>
          <institution content-type="original">Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP - Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Marina Politi Okoshi &#8226;</bold> Departamento de Cl&#237;nica M&#233;dica. Rubi&#227;o J&#250;nior, S/N. CEP 18618-000, Rubi&#227;o J&#250;nior, Botucatu, SP - Brasil E-mail: <email>mpoliti@fmb.unesp.br</email>
				</corresp>
      </author-notes>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Doen&#231;as Cardiovasculares</kwd>
        <kwd>Insufici&#234;ncia Card&#237;aca</kwd>
        <kwd>Exerc&#237;cio/preven&#231;&#227;o e controle</kwd>
        <kwd>Aptid&#227;o F&#237;sica</kwd>
        <kwd>Remodela&#231;&#227;o Ventricular</kwd>
        <kwd>Qualidade de Vida</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>FAPESP</funding-source>
          <award-id>2014/21972-3</award-id>
          <award-id>2014/23592-3</award-id>
        </award-group>
        <award-group>
          <funding-source>CNPq</funding-source>
          <award-id>310876/2018-4</award-id>
          <award-id>153424/2018-4</award-id>
        </award-group>
      </funding-group>
    </front-stub>
    <body>
      <p>Atualmente, as doen&#231;as cardiovasculares constituem o maior agravo para a sa&#250;de, estando diretamente envolvidas em mais de 17 milh&#245;es de mortes a cada ano, o que representa metade de todas as mortes por doen&#231;as n&#227;o transmiss&#237;veis.<xref ref-type="bibr" rid="B1">1</xref> Al&#233;m de seus efeitos no bem-estar individual, as doen&#231;as cardiovasculares s&#227;o respons&#225;veis por elevado impacto econ&#244;mico. Estudo recentemente publicado mostrou que, no Brasil, apenas quatro doen&#231;as - hipertens&#227;o arterial, infarto do mioc&#225;rdio, fibrila&#231;&#227;o atrial e insufici&#234;ncia card&#237;aca - totalizaram custo financeiro estimado em 56,2 bilh&#245;es de reais no ano de 2015.<xref ref-type="bibr" rid="B1">1</xref>
			</p>
      <p>O tratamento das doen&#231;as cardiovasculares envolve o uso de f&#225;rmacos espec&#237;ficos e a ades&#227;o a interven&#231;&#245;es n&#227;o farmacol&#243;gicas.<xref ref-type="bibr" rid="B2">2</xref> Este Editorial ser&#225; dedicado ao papel do exerc&#237;cio f&#237;sico no tratamento das doen&#231;as cardiovasculares. O Brasil ocupa posi&#231;&#227;o de destaque no cen&#225;rio mundial no estudo dos efeitos do exerc&#237;cio f&#237;sico em diferentes condi&#231;&#245;es cl&#237;nicas. Exerc&#237;cios v&#234;m sendo preconizados h&#225; d&#233;cadas para a promo&#231;&#227;o da sa&#250;de e o tratamento de diversas doen&#231;as cardiovasculares. A pr&#225;tica regular de exerc&#237;cios resulta em in&#250;meros benef&#237;cios como aumento da capacidade funcional e melhora na composi&#231;&#227;o corporal, resist&#234;ncia &#224; insulina, fun&#231;&#227;o endotelial, hipertens&#227;o arterial, estado antioxidante e qualidade de vida.<xref ref-type="bibr" rid="B3">3</xref><sup>-</sup><xref ref-type="bibr" rid="B9">9</xref> No caso da insufici&#234;ncia card&#237;aca, exerc&#237;cios passaram a ser preconizados h&#225; quase tr&#234;s d&#233;cadas no tratamento de pacientes est&#225;veis. Al&#233;m de aumentar a toler&#226;ncia aos esfor&#231;os, melhora a qualidade de vida e reduz hospitaliza&#231;&#245;es por insufici&#234;ncia card&#237;aca.<xref ref-type="bibr" rid="B2">2</xref> Apesar de grande n&#250;mero de estudos avaliando os efeitos do exerc&#237;cio, sua influ&#234;ncia em diferentes situa&#231;&#245;es de agress&#227;o card&#237;aca ainda n&#227;o est&#225; totalmente esclarecida.<xref ref-type="bibr" rid="B10">10</xref>
			</p>
      <p>Em artigos recentemente publicados neste peri&#243;dico, o papel do exerc&#237;cio f&#237;sico e seus mecanismos moleculares de a&#231;&#227;o foram avaliados em diferentes modelos experimentais de doen&#231;as card&#237;acas.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref><sup>-</sup><xref ref-type="bibr" rid="B13">13</xref> Efeitos ben&#233;ficos na remodela&#231;&#227;o card&#237;aca t&#234;m sido frequentemente observados, a exemplo de atenua&#231;&#227;o de hipertrofia mioc&#225;rdica e de disfun&#231;&#227;o do ventr&#237;culo esquerdo.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> Entretanto, resultados inesperados t&#234;m chamado a aten&#231;&#227;o para a necessidade de melhor esclarecer o assunto. Por exemplo, Rodrigues et al.,<xref ref-type="bibr" rid="B13">13</xref> submeteram camundongos <italic>knockout</italic> para receptor beta<sub>1</sub>-adren&#233;rgico card&#237;aco, que podem evoluir para insufici&#234;ncia card&#237;aca, a treinamento em esteira por oito semanas. Surpreendentemente, os animais <italic>knockout</italic> treinados tiveram aumento da capacidade funcional e da contratilidade mioc&#225;rdica superior ao dos animais-controle treinados. Como est&#237;mulo exagerado da contratilidade pode levar a deteriora&#231;&#227;o da fun&#231;&#227;o card&#237;aca a longo prazo, estudos adicionais s&#227;o necess&#225;rios para definir o papel do exerc&#237;cio na fun&#231;&#227;o card&#237;aca em camundongos <italic>knockout</italic> para o receptor beta<sub>1</sub>-adren&#233;rgico em per&#237;odos mais avan&#231;ados de vida.</p>
      <p>T&#243;picos de grande incerteza em rela&#231;&#227;o &#224; prescri&#231;&#227;o de exerc&#237;cios incluem intensidade e dura&#231;&#227;o do exerc&#237;cio. Recentemente, Ellingsen et al.,<xref ref-type="bibr" rid="B15">15</xref> publicaram o primeiro estudo multic&#234;ntrico randomizado comparando os efeitos do treinamento intervalado de alta intensidade (popularmente conhecido como HIIT, <italic>high-intensity interval training</italic>) com aqueles do treinamento cont&#237;nuo em moderada intensidade ou recomenda&#231;&#227;o para exerc&#237;cios regulares em pacientes com insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o reduzida. Em ambos os grupos de treinamento espec&#237;fico, os resultados foram apenas moderadamente superiores &#224; recomenda&#231;&#227;o para exerc&#237;cio regular. Al&#233;m disso, 51% dos pacientes no grupo HIIT se exercitaram abaixo da frequ&#234;ncia card&#237;aca prescrita, e 80% do grupo de treinamento cont&#237;nuo em moderada intensidade treinaram em frequ&#234;ncia acima de seus alvos. Assim, considerando que o HIIT n&#227;o foi superior ao treinamento cont&#237;nuo em moderada intensidade em reduzir o processo de remodela&#231;&#227;o ou melhorar desfechos cl&#237;nicos, e a dificuldade em obter ades&#227;o &#224; intensidade prescrita, os autores recomendam que o treinamento cont&#237;nuo em moderada intensidade deva permanecer como a modalidade padr&#227;o para pacientes com insufici&#234;ncia card&#237;aca cr&#244;nica.</p>
      <p>Outro fator ainda n&#227;o esclarecido &#233; se a pr&#225;tica de exerc&#237;cio em per&#237;odos curtos e intensos repetidos no decorrer do dia, denominada exerc&#237;cio acumulado, pode ser uma alternativa para pessoas sedent&#225;rias. Martinez et al.,<xref ref-type="bibr" rid="B16">16</xref> observaram que tanto o exerc&#237;cio cont&#237;nuo como o acumulado melhoraram a aptid&#227;o f&#237;sica de ratos saud&#225;veis. Entretanto, somente o exerc&#237;cio cont&#237;nuo foi capaz de reduzir o ganho de peso corporal e melhorar a fun&#231;&#227;o endotelial. Aortas retiradas do grupo submetido a exerc&#237;cio cont&#237;nuo apresentaram redu&#231;&#227;o da resposta contr&#225;til &#224; norepinefrina e aumento do relaxamento induzido por acetilcolina, o que n&#227;o foi observado no grupo treinado por exerc&#237;cio acumulado.<xref ref-type="bibr" rid="B16">16</xref>
			</p>
      <p>Consenso maior se observa na literatura em rela&#231;&#227;o ao papel do exerc&#237;cio f&#237;sico sobre o sistema vascular. Lemos et al.,<xref ref-type="bibr" rid="B12">12</xref> mostraram que o exerc&#237;cio aer&#243;bico regular, por nove semanas, levou a atenua&#231;&#227;o da atividade simp&#225;tica e redu&#231;&#227;o da resist&#234;ncia vascular, contribuindo, portanto, para diminui&#231;&#227;o da press&#227;o arterial de ratos espontaneamente hipertensos. Tamb&#233;m o treinamento resistido foi efetivo em melhorar a resposta bradic&#225;rdica e a sensibilidade barorreflexa de ratos espontaneamente hipertensos.<xref ref-type="bibr" rid="B11">11</xref> Entretanto, o fato de que estes efeitos n&#227;o foram acompanhados por redu&#231;&#227;o da press&#227;o arterial sist&#234;mica<xref ref-type="bibr" rid="B11">11</xref> sugere que o exerc&#237;cio aer&#243;bico &#233; superior ao resistido no controle da hipertens&#227;o arterial.</p>
      <p>Apesar dos grandes avan&#231;os no entendimento dos efeitos do exerc&#237;cio f&#237;sico no sistema cardiovascular saud&#225;vel ou submetido a diferentes tipos de agress&#227;o, ainda estamos longe de esclarecer os mecanismos de a&#231;&#227;o do exerc&#237;cio f&#237;sico e de cientificamente definir a melhor prescri&#231;&#227;o para pacientes com doen&#231;a cardiovascular.</p>
    </body>
    <back>
      <ack>
        <title>Agradecimentos</title>
        <p>Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo - FAPESP (Proc. n&#186; 2014/21972-3 e 2014/23592-3); Conselho Nacional de Desenvolvimento Cient&#237;fico e Tecnol&#243;gico - CNPq (Proc. n&#186; 310876/2018-4 e 153424/2018-4).</p>
      </ack>
    </back>
  </sub-article>
</article>
