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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">NcpLgsLqGc488rRPtzXXwcv</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2020000400645</article-id>
      <article-id pub-id-type="publisher-id">abc.20200177</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20200177</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Transplate Card&#237;aco e a &#8220;C&#226;mara Secreta&#8221;: Como a Avalia&#231;&#227;o Ecocardiogr&#225;fica do Ventr&#237;culo Direito pode Revelar a Rejei&#231;&#227;o Celular Aguda</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-4543-4684</contrib-id>
          <name>
            <surname>Moreira</surname>
            <given-names>Henrique Turin</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2526-0656</contrib-id>
          <name>
            <surname>Romano</surname>
            <given-names>Minna Moreira Dias</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgdiv1">Faculdade de Medicina de Ribeir&#227;o Preto</institution>
        <institution content-type="orgname">USP</institution>
        <addr-line>
          <named-content content-type="city">Ribeir&#227;o Preto</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Faculdade de Medicina de Ribeir&#227;o Preto USP, Ribeir&#227;o Preto, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia:Minna Moreira Dias Romano &#8226; Campus Universit&#225;rio HCRP-USP - CEP 14048-900 E-mail: <email>minna@fmrp.usp.br</email>
				</corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>29</day>
        <month>05</month>
        <year>2020</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>04</month>
        <year>2020</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>04</month>
        <year>2020</year>
      </pub-date>
      <volume>114</volume>
      <issue>4</issue>
      <fpage>645</fpage>
      <lpage>646</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 Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. </license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <kwd>Rejei&#231;&#227;o Celular Aguda</kwd>
        <kwd>Transplante do Cora&#231;&#227;o</kwd>
        <kwd>Bi&#243;psia Endomioc&#225;rdica</kwd>
        <kwd>Rejei&#231;&#227;o do Enxerto</kwd>
        <kwd>Ecocardiografia/m&#233;todos</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="14"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>Embora o transplante (Tx) card&#237;aco tenha alcan&#231;ado grande evolu&#231;&#227;o t&#233;cnica e cient&#237;fica nas &#250;ltimas d&#233;cadas, a rejei&#231;&#227;o celular aguda (RCA) ainda representa uma importante amea&#231;a aos pacientes submetidos a esse procedimento. Protocolos de rastreio de rejei&#231;&#227;o aguda associados &#224; terap&#234;utica imunossupressora precoce s&#227;o essenciais para o sucesso do mesmo. No entanto, a bi&#243;psia endomioc&#225;rdica, embora dispendiosa e invasiva, ainda &#233; m&#233;todo de refer&#234;ncia para o rastreio da RCA.</p>
    <p>A RCA relaciona-se a danos incipientes na fun&#231;&#227;o mioc&#225;rdica,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> que podem n&#227;o ser detectados pelas t&#233;cnicas ecocardiogr&#225;ficas convencionais de an&#225;lise da fun&#231;&#227;o mioc&#225;rdica. A deforma&#231;&#227;o mioc&#225;rdica, analisada pela t&#233;cnica de rastreamento de pontos, &#233; capaz de detectar disfun&#231;&#227;o mioc&#225;rdica incipiente em diversas patologias, dentre elas, a RCA p&#243;s Tx card&#237;aco.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
    <p>Em recente metan&#225;lise envolvendo 10 estudos com semelhan&#231;as metodol&#243;gicas, Elkaryone et al.,<sup><xref ref-type="bibr" rid="B3">3</xref></sup> analisaram 511 pacientes e 1.267 bi&#243;psias endomioc&#225;rdicas. A sensibilidade da deforma&#231;&#227;o longitudinal global do ventr&#237;culo esquerdo (VE), expressa pelo GLS, para detectar RCA diagnosticada por bi&#243;psia endomioc&#225;rdica foi de 78%, com especificidade de 68%.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Ademais, as altera&#231;&#245;es de deforma&#231;&#227;o mioc&#225;rdica do VE j&#225; foram demonstradas como preditores independentes de desfechos cl&#237;nicos ap&#243;s o Tx card&#237;aco.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Importante ressaltar que nem sempre as imagens ecocardiogr&#225;ficas permitem a an&#225;lise de deforma&#231;&#227;o mioc&#225;rdica nesta popula&#231;&#227;o, uma vez que o cora&#231;&#227;o transplantado pode estar em posi&#231;&#227;o mais medial na cavidade tor&#225;cica, dificultando a obten&#231;&#227;o de imagens de boa qualidade, como previamente demonstrado.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> No entanto, a despeito de estudos das altera&#231;&#245;es de VE neste cen&#225;rio, menos conhecimento foi acumulado at&#233; o momento atual acerca das correla&#231;&#245;es entre altera&#231;&#245;es do ventr&#237;culo direito (VD) e RCA ap&#243;s Tx card&#237;aco. &#201; reconhecido o aumento das dimens&#245;es desta c&#226;mara associado &#224; leve redu&#231;&#227;o de sua fun&#231;&#227;o sist&#243;lica na evolu&#231;&#227;o natural de pacientes ap&#243;s o Tx card&#237;aco.<sup><xref ref-type="bibr" rid="B5">5</xref> - <xref ref-type="bibr" rid="B7">7</xref></sup></p>
    <p>O trabalho de Carrion et al.,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> demonstram que pacientes com sinais de RCA significativa pela bi&#243;psia endomioc&#225;rdica apresentam redu&#231;&#227;o de par&#226;metros de fun&#231;&#227;o diast&#243;lica ventricular esquerda, al&#233;m de sinais de aumento da espessura da parede posterior do VE, comparados aos sem rejei&#231;&#227;o significativa. Divergente de outros estudos, n&#227;o houve diferen&#231;a significativa da deforma&#231;&#227;o longitudinal do VE entre este grupo e aquele que n&#227;o apresentou sinais de rejei&#231;&#227;o significativa. Vale ressaltar que a maioria dos estudos pr&#233;vios usou, para an&#225;lise da deforma&#231;&#227;o mioc&#225;rdica, <italic>softwares</italic> vendedores-dedicados, enquanto Carrion et al.,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> usaram <italic>software</italic> independente de vendedor na an&#225;lise das imagens,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> o que poderia explicar, pelo menos em parte, as diverg&#234;ncias citadas, uma vez que ainda n&#227;o h&#225; padroniza&#231;&#227;o entre <italic>softwares</italic> de diferentes vendedores.<sup><xref ref-type="bibr" rid="B8">8</xref></sup></p>
    <p>Outra poss&#237;vel fonte de diverg&#234;ncia entre o presente estudo e investiga&#231;&#245;es pr&#233;vias &#233; a metodologia empregada para a medida da deforma&#231;&#227;o mioc&#225;rdica. Carrion et al.,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> realizaram a medida do pico sist&#243;lico da deforma&#231;&#227;o mioc&#225;rdica, assim como recomendado pelas mais recentes diretrizes internacionais,<sup><xref ref-type="bibr" rid="B9">9</xref></sup> enquanto outros trabalhos utilizaram o pico de deforma&#231;&#227;o mioc&#225;rdica de todo o ciclo card&#237;aco.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Ainda, o <italic>software</italic> utilizado para an&#225;lises por Carrion et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> baseia-se na an&#225;lise da deforma&#231;&#227;o endoc&#225;rdica, enquanto outros <italic>softwares</italic> dispon&#237;veis, e historicamente mais utilizados, analisaram a deforma&#231;&#227;o mioc&#225;rdica de toda a espessura da parede, incluindo todas as suas camadas, tamb&#233;m chamada deforma&#231;&#227;o transmural.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> Neste estudo os par&#226;metros ecocardiogr&#225;ficos convencionais de an&#225;lise da fun&#231;&#227;o do VD, assim como a deforma&#231;&#227;o mioc&#225;rdica do VD, apresentaram-se significativamente reduzidos no grupo de pacientes com sinais de RCA em compara&#231;&#227;o com aqueles sem rejei&#231;&#227;o significativa.11 Al&#233;m disso, o grupo com RCA moderada tamb&#233;m mostrou altera&#231;&#245;es sugestivas de pior fun&#231;&#227;o diast&#243;lica do VE em compara&#231;&#227;o com o grupo sem rejei&#231;&#227;o significativa.</p>
    <p>Dessa forma, permanece a d&#250;vida se o envolvimento da fun&#231;&#227;o sist&#243;lica do VD &#233; prim&#225;rio, devido &#224; RCA, ou secund&#225;rio ao aumento retr&#243;grado das press&#245;es de enchimento do VE. Al&#233;m disso, n&#227;o apenas a deforma&#231;&#227;o mioc&#225;rdica do VD, mas tamb&#233;m os par&#226;metros convencionais de avalia&#231;&#227;o funcional dessa c&#226;mara card&#237;aca mostraram-se significativamente diferente entre os dois grupos estudados por Carrion et al.,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Estudos pr&#233;vios demonstram que a deforma&#231;&#227;o sist&#243;lica do VD, especialmente de sua parede livre, apresenta maior correla&#231;&#227;o com a fun&#231;&#227;o sist&#243;lica do VD, avaliada por m&#233;todos de refer&#234;ncia, em compara&#231;&#227;o com par&#226;metros ecocardiogr&#225;ficos convencionais, tanto em cardiopatias isqu&#234;micas, quanto em n&#227;o-isqu&#234;micas.<sup><xref ref-type="bibr" rid="B12">12</xref> - <xref ref-type="bibr" rid="B14">14</xref></sup> Embora a compara&#231;&#227;o da acur&#225;cia diagn&#243;stica dos par&#226;metros funcionais do VD para diagn&#243;stico da RCA n&#227;o tenha sido abordada por Carrion et al.,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> essa quest&#227;o &#233; ponto relevante a ser esclarecido em estudos futuros, para desse modo nortear o emprego dessas t&#233;cnicas na rotina cl&#237;nica p&#243;s Tx card&#237;aco.</p>
    <p>Assim, para uma ci&#234;ncia que h&#225; pouco tempo conseguiu reconhecer e &#8220;apontar&#8221; para a &#8220;c&#226;mara secreta&#8221;, o VD, o trabalho de Carrion et al.,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> refor&#231;a a import&#226;ncia da avalia&#231;&#227;o ecocardiogr&#225;fica da mesma para a detec&#231;&#227;o n&#227;o invasiva da disfun&#231;&#227;o mioc&#225;rdica incipiente relacionada &#224; RCA em pacientes em seguimento ap&#243;s Tx card&#237;aco.</p>
  </body>
  <back>
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    <fn-group>
      <fn fn-type="other">
        <p>
          <italic>Minieditorial referente ao artigo: Disfun&#231;&#227;o Ventricular Direita e Rejei&#231;&#227;o em Transplante Card&#237;aco</italic>
        </p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Heart Transplantation and the &#8220;The Secret Chamber&#8221;: How Echocardiographic Assessment of the Right Ventricle Can Reveal Acute Cell Rejection</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-4543-4684</contrib-id>
          <name>
            <surname>Moreira</surname>
            <given-names>Henrique Turin</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2526-0656</contrib-id>
          <name>
            <surname>Romano</surname>
            <given-names>Minna Moreira Dias</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Faculdade de Medicina de Ribeir&#227;o Preto USP, Ribeir&#227;o Preto, SP &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Minna Moreira Dias Romano &#8226; Campus Universit&#225;rio HCRP-USP - Postal Code 14048-900 E-mail: minna@fmrp.usp.br</corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Cellular Acute Rejection</kwd>
        <kwd>Heart Transplantation</kwd>
        <kwd>Endomyocardial Biopsy</kwd>
        <kwd>Graft Rejection</kwd>
        <kwd>Echocardiography/methods</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Although heart transplantation (Tx) has achieved great technical and scientific evolution in recent decades, acute cell rejection (ACR) still represents an important threat to patients submitted to this procedure. Acute rejection screening protocols associated with early immunosuppressive therapy are essential for Tx success. However, endomyocardial biopsy, although expensive and invasive, is still a reference method for the screening of ACR.</p>
      <p>ACR is related to incipient damage in myocardial function,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> which may not be detected by conventional echocardiographic techniques for myocardial function analysis. Myocardial deformation, analyzed by the speckle tracking technique, is able to detect incipient myocardial dysfunction in several pathologies, among them, ACR after cardiac Tx.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
      <p>In a recent meta-analysis of 10 studies with methodological similarities, Elkaryone et al.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> analyzed 511 patients and 1,267 endomyocardial biopsies. The sensitivity of the global longitudinal deformation of the left ventricle (LV), expressed by the GLS, to detect ACR diagnosed by endomyocardial biopsy was 78%, with a specificity of 68%.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Moreover, changes in LV myocardial deformation have already been demonstrated as independent predictors of clinical outcomes after heart Tx.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> It is important to note that echocardiographic images do not always allow the analysis of myocardial deformation in this population, since the transplanted heart may be in more medial position in the thoracic cavity, making it difficult to obtain good quality images, as previously demonstrated.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> However, despite studies of LV changes in this scenario, less knowledge has been accumulated to date about the correlations between changes in the right ventricle (RV) and ACR after heart Tx. The increase in the dimensions of this chamber associated with the slight reduction of its systolic function in the natural evolution of patients after cardiac Tx has been established.<sup><xref ref-type="bibr" rid="B5">5</xref> - <xref ref-type="bibr" rid="B7">7</xref></sup></p>
      <p>The work by Carrion et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> demonstrate that patients with signs of significant ACR by endomyocardial biopsy have reduced left ventricular diastolic function parameters, in addition to signs of increased LV posterior wall thickness, when compared to those without significant rejection. Unlike other studies, there was no significant difference in the LV longitudinal deformation between this group and the one that did not show signs of significant rejection. It is worth mentioning that most of the previous studies used, for the analysis of myocardial deformation, vendor-dedicated software, while Carrion et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> used vendor-independent software to analyze the images,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> which could explain the aforementioned differences, at least in part, since there is still no standardization between software from different vendors.<sup><xref ref-type="bibr" rid="B8">8</xref></sup></p>
      <p>Another possible source of divergence between the present study and previous investigations is the methodology used to measure myocardial deformation. Carrion et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> performed the measurement at the systolic peak of myocardial deformation, as recommended by the most recent international guidelines,<sup><xref ref-type="bibr" rid="B9">9</xref></sup> while other studies used the peak myocardial deformation of the entire cardiac cycle.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Also, the software used for the analysis by Carrion et al. is based on the analysis of endocardial deformation, while other software available, and historically more often used, analyzed the myocardial deformation of the entire wall thickness, including all its layers, also called transmural deformation.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> In this study, the conventional echocardiographic parameters for the analysis of the RV function, as well as the RV myocardial deformation, were significantly reduced in the group of patients with signs of ACR, when compared to those without significant rejection.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> Moreover, the group with moderate ACR also showed changes suggestive of worse LV diastolic function, when compared to the group without significant rejection.</p>
      <p>Thus, the question remains whether the involvement of RV systolic function is a primary one, due to ACR, or secondary to the retrograde increase in LV filling pressures. Additionally, not only the myocardial deformation of the RV, but also the conventional parameters for the functional evaluation of this cardiac chamber have shown be significantly different between the two groups studied by Carrion et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Previous studies have shown that RV systolic deformation, especially of its free wall, has a greater correlation with RV systolic function, assessed by reference methods, in comparison with conventional echocardiographic parameters, both in ischemic and non-ischemic heart diseases.<sup><xref ref-type="bibr" rid="B12">12</xref> - <xref ref-type="bibr" rid="B14">14</xref></sup> Although the comparison of the diagnostic accuracy of the RV functional parameters for ACR diagnosis has not been addressed by Carrion et al.,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> this issue is a relevant point to be clarified in future studies, aiming to guide the use of these techniques in the post-heart Tx clinical routine.</p>
      <p>Thus, for a science that recently managed to recognize and &#8220;point&#8221; to the &#8220;chamber of secrets&#8221;, i.e., the RV, the work of Carrion et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> reinforces the importance of its echocardiographic evaluation for the non-invasive detection of incipient myocardial dysfunction related to ACR in patients being followed after heart Tx.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>
            <italic>Short Editorial related to the article: Impaired Right Ventricular Function in Heart Transplant Rejection</italic>
          </p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
