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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 specific-use="scielo-v3" pub-id-type="publisher-id">fwq9zXXxfcqfTKzkPtsjgXd</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2024000800203</article-id>
      <article-id pub-id-type="other">00203</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20240452</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Precisamos de Novos Par&#226;metros Ecocardiogr&#225;ficos para Transplantados sem Rejei&#231;&#227;o?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3076-9860</contrib-id>
          <name>
            <surname>H&#252;ning</surname>
            <given-names>Alberto Rodolpho</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-6521-2870</contrib-id>
          <name>
            <surname>Rosa</surname>
            <given-names>Vitor Emer Egypto</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina</institution>
          <institution content-type="orgdiv2">Hospital das Cl&#237;nicas HCFMUSP</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Instituto do Cora&#231;&#227;o (InCor), Hospital das Cl&#237;nicas HCFMUSP, Faculdade de Medicina, Universidade de S&#227;o Paulo, S&#227;o Paulo, SP - Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><label>Correspond&#234;ncia: Vitor Emer Egypto Rosa &#8226;</label> Instituto do Cora&#231;&#227;o (InCor), Hospital das Cl&#237;nicas HCFMUSP, Faculdade de Medicina, Universidade de S&#227;o Paulo - Av. Dr. Eneas Carvalho de Aguiar, 44. CEP <postal-code>05403-900</postal-code>, Cerqueira C&#233;sar, S&#227;o Paulo, SP - Brasil E-mail: <email>vitoremer@yahoo.com.br</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>23</day>
        <month>09</month>
        <year>2024</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <year>2024</year>
      </pub-date>
      <volume>121</volume>
      <issue>8</issue>
      <elocation-id>e20240452</elocation-id>
      <history>
        <date date-type="received">
          <day>27</day>
          <month>06</month>
          <year>2024</year>
        </date>
        <date date-type="rev-recd">
          <day>07</day>
          <month>08</month>
          <year>2024</year>
        </date>
        <date date-type="accepted">
          <day>07</day>
          <month>08</month>
          <year>2024</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xml:lang="en" xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Transplante Card&#237;aco</kwd>
        <kwd>Ecocardiograma</kwd>
        <kwd>Strain Longitudinal</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="11"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>O transplante card&#237;aco representa a principal modalidade terap&#234;utica para pacientes com insufici&#234;ncia card&#237;aca terminal que n&#227;o respondem ao manejo m&#233;dico e cir&#250;rgico maximizado.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> O Brasil possui um dos mais extensos sistemas de sa&#250;de p&#250;blica para transplante de &#243;rg&#227;os do mundo, com quase todos os procedimentos realizados no &#226;mbito do Sistema &#218;nico de Sa&#250;de (SUS). Contudo, ainda faltam estudos que validem par&#226;metros ecocardiogr&#225;ficos normais nesta popula&#231;&#227;o, e este foi o tema do estudo realizado por Dall&#8217;Orto et al.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
      <sec>
        <title>Ecocardiografia transtor&#225;cica em transplante card&#237;aco</title>
        <p>A ecocardiografia transtor&#225;cica &#233; essencial na avalia&#231;&#227;o de receptores de transplante card&#237;aco, embora com limita&#231;&#245;es inerentes. Embora a normaliza&#231;&#227;o da fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo (FEVE) p&#243;s-transplante card&#237;aco esteja associada a um progn&#243;stico favor&#225;vel, existem limita&#231;&#245;es significativas na avalia&#231;&#227;o da fun&#231;&#227;o sist&#243;lica e diast&#243;lica do ventr&#237;culo esquerdo (VE) e do ventr&#237;culo direito, massa ventricular esquerda, doen&#231;a card&#237;aca valvular, hipertens&#227;o arterial pulmonar e efus&#227;o peric&#225;rdica.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup></p>
        <p>Ap&#243;s o transplante, a bi&#243;psia endomioc&#225;rdica &#233; realizada rotineiramente para vigil&#226;ncia da rejei&#231;&#227;o celular e humoral, a partir da segunda semana e aos 30 dias, 90 dias, 6 meses e 12 meses depois, ou quando h&#225; suspeita (p. ex., novo in&#237;cio de disfun&#231;&#227;o ventricular). Al&#233;m disso, a bi&#243;psia endomioc&#225;rdica tamb&#233;m &#233; realizada para diagnosticar outras patologias, como miocardite, cardiomiopatias infiltrativas, insufici&#234;ncia card&#237;aca de in&#237;cio recente, neoplasias card&#237;acas, arritmias ventriculares inexplic&#225;veis, cardiomiopatia hipertr&#243;fica e continua sendo o padr&#227;o ouro para detectar rejei&#231;&#227;o aguda de aloenxerto.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
      </sec>
      <sec>
        <title>Speckle Tracking e novas modalidades de ecocardiografia</title>
        <p>As modalidades emergentes avan&#231;aram, mas a sua aplica&#231;&#227;o em receptores de transplante card&#237;aco &#233; limitada. O strain longitudinal global (SLG) avaliado por meio do <italic>speckle tracking</italic> emergiu como um complemento valioso para a avalia&#231;&#227;o da fun&#231;&#227;o ventricular esquerda, oferecendo maior reprodutibilidade em compara&#231;&#227;o com a medi&#231;&#227;o tradicional da FEVE.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> O strain longitudinal &#233; utilizado para avaliar a fun&#231;&#227;o sist&#243;lica global do VE por meio da ecocardiografia, mostrando-se altamente &#250;til para estratifica&#231;&#227;o progn&#243;stica em diversas doen&#231;as e para detec&#231;&#227;o precoce de envolvimento mioc&#225;rdico. O SLG &#233; a medida mais comumente usada, e o pico do SLG descreve as altera&#231;&#245;es relativas na deforma&#231;&#227;o mioc&#225;rdica do VE entre a di&#225;stole final e a s&#237;stole final. Um valor SLG normal &#233; definido como maior ou igual a 20% em magnitude (ou &#8804; -20% quando considerado negativo). Espera-se um valor em torno de -20% em um indiv&#237;duo normal, mas o limite inferior de normalidade pode variar de -11% a -18%, dependendo do software e equipamento utilizado. Em rela&#231;&#227;o ao ventr&#237;culo direito (VD), o SLG &#233; adaptado das medidas do VE. SLG VD normalmente se refere &#224; m&#233;dia da parede livre e dos segmentos septais ou apenas da parede livre. Um SLG VD inferior a 20% (valor absoluto) &#233; considerado anormal.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
        <p>Os &#237;ndices de trabalho mioc&#225;rdico (MWI) avaliam a demanda mioc&#225;rdica de oxig&#234;nio e a fun&#231;&#227;o card&#237;aca, demonstrando superioridade sobre o SLG, pois &#233; respons&#225;vel pela deforma&#231;&#227;o mioc&#225;rdica juntamente com a p&#243;s-carga.<sup><xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup> &#201; calculado incorporando a press&#227;o ventricular esquerda n&#227;o invasiva obtida por meio de manguito autom&#225;tico com o strain do VE, fornecendo &#237;ndices associados &#224; curva strain-press&#227;o. O &#237;ndice global de trabalho (GWI), o trabalho construtivo global (GCW), o desperd&#237;cio global de trabalho (GWW) e a efici&#234;ncia global do trabalho (GWE) s&#227;o estimados a partir dos ciclos de press&#227;o-deforma&#231;&#227;o do LV. Os valores do trabalho mioc&#225;rdico (MW) podem variar, variando de 1270 mmHg% (homens) e 1310 mmHg% (mulheres) para GWI a 238 mmHg (homens) e 239 mmHg (mulheres) para GWW.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
      </sec>
      <sec>
        <title>Estudo atual</title>
        <p>O estudo teve como objetivo principal avaliar o strain em pacientes transplantados card&#237;acos sem rejei&#231;&#227;o em compara&#231;&#227;o com indiv&#237;duos saud&#225;veis. Uma redu&#231;&#227;o significativa nos valores de strain foi observada no grupo transplantado (SLG VE11,99&#177;2,74) em compara&#231;&#227;o ao grupo controle e aos padr&#245;es normais descritos nas diretrizes,<sup><xref ref-type="bibr" rid="B4">4</xref></sup> apesar da FEVE preservada (64,52&#177;6,88%). Al&#233;m disso, o grupo transplantado apresentou diferen&#231;as em outras vari&#225;veis ecocardiogr&#225;ficas, como redu&#231;&#227;o do strain da parede livre do VD e &#237;ndices de trabalho mioc&#225;rdico, maior tamanho do &#225;trio esquerdo e aumento do &#237;ndice de massa e espessura relativa da parede. Inicialmente foram inclu&#237;dos 100 pacientes; no entanto, 35 foram exclu&#237;dos devido &#224; rejei&#231;&#227;o confirmada por bi&#243;psia.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
        <p>Os pontos fortes do estudo incluem uma metodologia robusta, comparando receptores de transplante sem rejei&#231;&#227;o (confirmada por bi&#243;psia endomioc&#225;rdica) a indiv&#237;duos saud&#225;veis atrav&#233;s de ecocardiografia realizada por tr&#234;s examinadores treinados, cegos para os resultados da bi&#243;psia. O uso de par&#226;metros ecocardiogr&#225;ficos inovadores do estudo NORRE<sup><xref ref-type="bibr" rid="B10">10</xref></sup> &#233; interessante, sendo o primeiro a aplicar esses par&#226;metros em transplantados sem rejei&#231;&#227;o (com mais de 50% dos casos por doen&#231;a de Chagas) e compar&#225;-los com indiv&#237;duos saud&#225;veis.</p>
        <p>No entanto, o estudo tem limita&#231;&#245;es. As caracter&#237;sticas basais da popula&#231;&#227;o saud&#225;vel diferem substancialmente daquelas dos transplantados, principalmente no &#237;ndice de massa corporal e na &#225;rea de superf&#237;cie corporal, comprometendo a avalia&#231;&#227;o de par&#226;metros n&#227;o indexados. Al&#233;m disso, faltam informa&#231;&#245;es sobre indiv&#237;duos saud&#225;veis, como comorbidades e uso de medicamentos. O tamanho da amostra &#233; pequeno e um grupo controle maior poderia reduzir as diferen&#231;as nas caracter&#237;sticas cl&#237;nicas. Limita&#231;&#245;es menores inclu&#237;ram a incapacidade de realizar medi&#231;&#245;es da fun&#231;&#227;o diast&#243;lica em mais de 50% dos pacientes do grupo de transplante e a natureza unic&#234;ntrica do estudo.</p>
        <p>As conclus&#245;es do estudo s&#227;o intrigantes: a redu&#231;&#227;o do SLG do VE e do VD e a diminui&#231;&#227;o do MWI em receptores de transplante sem rejei&#231;&#227;o apoiam a hip&#243;tese de potencial insufici&#234;ncia card&#237;aca diast&#243;lica p&#243;s-operat&#243;ria, com inflama&#231;&#227;o inicial como previamente evidenciado por Ingvarsson et al.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> No entanto, mais estudos com coortes maiores de pacientes, diversos softwares ecocardiogr&#225;ficos e desenho multic&#234;ntrico s&#227;o necess&#225;rios para validar esses achados.</p>
      </sec>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>Minieditorial referente ao artigo: Comparac&#227;o dos Par&#226;metros Ecocardiogr&#225;ficos Convencionais e com Speckle Tracking entre Indiv&#237;duos Saud&#225;veis e Transplantados Card&#237;acos sem Rejei&#231;&#227;o</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" id="S1" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20240452i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Do We Need New Echocardiographic Parameters for Transplant Recipients without Rejection?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3076-9860</contrib-id>
          <name>
            <surname>H&#252;ning</surname>
            <given-names>Alberto Rodolpho</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-6521-2870</contrib-id>
          <name>
            <surname>Rosa</surname>
            <given-names>Vitor Emer Egypto</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff2">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto do Cora&#231;&#227;o (InCor), Hospital das Cl&#237;nicas HCFMUSP, Faculdade de Medicina, Universidade de S&#227;o Paulo, S&#227;o Paulo, SP - Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><label>Mailing Address: Vitor Emer Egypto Rosa &#8226;</label> Instituto do Cora&#231;&#227;o (InCor), Hospital das Cl&#237;nicas HCFMUSP, Faculdade de Medicina, Universidade de S&#227;o Paulo - Av. Dr. Eneas Carvalho de Aguiar, 44. Potal Code <postal-code>05403-900</postal-code>, Cerqueira C&#233;sar, S&#227;o Paulo, SP - Brazil E-mail: <email>vitoremer@yahoo.com.br</email></corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Heart Transplant</kwd>
        <kwd>Echocardiography</kwd>
        <kwd>Longitudinal Strain</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Heart transplant represents the principal therapeutic modality for patients with end-stage heart failure unresponsive to maximized medical and surgical management.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Brazil boasts one of the most extensive public health systems for organ transplantation globally, with nearly all procedures conducted under the Unified Health System (SUS). However, there is still a lack of studies validating normal echocardiographic parameters in this population, and this was the topic of the study conducted by Dall&#8217;Orto et al.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
        <sec>
          <title>Transthoracic echocardiography in heart transplant</title>
          <p>Transthoracic echocardiography (TTE) is essential for assessing heart transplant recipients, albeit with inherent limitations. While normalization of left ventricular ejection fraction (LVEF) post-heart transplant is associated with a favorable prognosis, significant limitations exist in evaluating left ventricular and right ventricular systolic and diastolic function, left ventricular mass, valvular heart disease, pulmonary arterial hypertension, and pericardial effusion.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup></p>
          <p>After transplantation, endomyocardial biopsy is routinely performed for surveillance of cellular and humoral rejection, starting from the second week and at 30 days, 90 days, 6 months, and 12 months thereafter, or when there is suspicion (e.g., new onset ventricular dysfunction). Additionally, endomyocardial biopsy is also conducted to diagnose other pathologies such as myocarditis, infiltrative cardiomyopathies, recent-onset heart failure, cardiac neoplasms, unexplained ventricular arrhythmias, hypertrophic cardiomyopathy and remains the gold standard for detecting acute allograft rejection.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
        </sec>
        <sec>
          <title>Speckle Tracking and new echocardiography modalities</title>
          <p>Emerging modalities have advanced, yet their application in cardiac transplant recipients is limited. Global longitudinal strain (GLS) assessed via speckle tracking has emerged as a valuable adjunct for left ventricular (LV) function evaluation, offering enhanced reproducibility compared to traditional LVEF measurement.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Longitudinal strain is used to evaluate the global systolic function of the LV via echocardiography, proving highly useful for prognostic stratification in various diseases and for detecting early myocardial involvement. GLS is the most commonly used measure, and the GLS peak describes the relative changes in LV myocardial deformation between end-diastole and end-systole. A normal GLS value is defined as greater than or equal to 20% in magnitude (or &#8804; -20% when considered negative). A value of around -20% is expected in a normal individual, but the lower limit of normality can range from -11% to -18%, depending on the software and equipment used. Regarding the right ventricle (RV), GLS is adapted from LV measurements. RV GLS typically refers to the average of the free wall and septal segments or just the free wall. An RV GLS less than 20% (absolute value) is considered abnormal.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
          <p>Myocardial work indices (MWI) evaluate myocardial oxygen demand and cardiac function, demonstrating superiority over GLS as it accounts for myocardial deformation alongside afterload.<sup><xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup> It is calculated by incorporating the non-invasive estimated left ventricular pressure obtained through an automatic cuff with the LV strain, providing indices associated with the strain-pressure curve. Global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE) are estimated from LV pressure&#8211;strain loops. The values of myocardial work (MW) can vary, ranging from 1270 mmHg% (men) and 1310 mmHg% (women) for GWI to 238 mmHg (men) and 239 mmHg (women) for GWW.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
        </sec>
        <sec>
          <title>Current Study</title>
          <p>The study primarily aimed to evaluate strain in heart transplant patients without rejection compared to healthy individuals. A significant reduction in strain values was observed in the transplant group (LV GLS 11.99&#177;2.74) compared to the control group and the normal standards described in guidelines,<sup><xref ref-type="bibr" rid="B4">4</xref></sup> despite preserved LVEF (64.52&#177;6.88%). Additionally, the transplant group exhibited differences in other echocardiographic variables as reduced RV free wall strain and myocardial work indices, larger left atrial size, and increased mass index and relative wall thickness. Initially, 100 patients were included; however, 35 were excluded due to biopsy-confirmed rejection.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
          <p>The study's strengths include a robust methodology, comparing transplant recipients without rejection (confirmed by endomyocardial biopsy) to healthy individuals via echocardiography conducted by three trained examiners, with echocardiographers blinded to biopsy results. The use of innovative echocardiographic parameters from the NORRE study<sup><xref ref-type="bibr" rid="B10">10</xref></sup> is significant, being the first to apply these parameters in transplant recipients without rejection (with over 50% of cases due to Chagas disease) and comparing them with healthy individuals.</p>
          <p>However, the study has limitations. The baseline characteristics of the healthy population differ substantially from those of the transplant recipients, particularly in body mass index and body surface area, jeopardizing the evaluation of non-indexed parameters. Additionally, there is a lack of information about healthy subjects, such as comorbidities and medication use. The sample size is small, and a larger control group could reduce differences in clinical characteristics. Minor limitations included the inability to perform diastolic function measurements in over 50% of the transplant group patients and the single-center nature of the study.</p>
          <p>The study's conclusions are intriguing: Reduced GLS of the LV and RV and decreased MWI in transplant recipients without rejection support the hypothesis of potential diastolic heart failure post-surgery, with initial inflammation as previously evidenced by Ingvarsson et al.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> However, further studies with larger patient cohorts, diverse echocardiographic software, and multicenter settings are necessary to validate these findings.</p>
        </sec>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other" id="fn2">
          <p>Short Editorial related to the article: Comparative Analysis of Conventional and Speckle Tracking Echocardiographic Variables between Patients with Unrejected Heart Transplants and Healthy Individuals</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
