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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">7tJhfMHp8K4jDN7N5qHmKmH</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2025000900306</article-id>
      <article-id pub-id-type="other">00306</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20240475</article-id>
      <article-id pub-id-type="other">abc.20240475</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>An&#225;lise da Mortalidade por M&#250;ltiplas Causas na Insufici&#234;ncia Card&#237;aca de Acordo com a Fra&#231;&#227;o de Eje&#231;&#227;o</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7668-4224</contrib-id>
          <name>
            <surname>Dutra</surname>
            <given-names>Giovanni Possamai</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7443-7270</contrib-id>
          <name>
            <surname>Gomes</surname>
            <given-names>Bruno Ferraz de Oliveira</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6799-7111</contrib-id>
          <name>
            <surname>Silva</surname>
            <given-names>Thiago Moreira Bastos da</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Peres</surname>
            <given-names>Leticia Souza</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rangel</surname>
            <given-names>Marco Ant&#244;nio Netto Armando</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Petriz</surname>
            <given-names>Jo&#227;o Luiz Fernandes</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Carmo</surname>
            <given-names>Plinio Resende do</given-names>
            <suffix>Junior</suffix>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nascimento</surname>
            <given-names>Emilia Matos</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pereira</surname>
            <given-names>Basilio de Bragan&#231;a</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-0737-6188</contrib-id>
          <name>
            <surname>Oliveira</surname>
            <given-names>Gl&#225;ucia Maria Moraes de</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <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 Federal do Rio de Janeiro</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Hospital Barra D&#8217;Or</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital Barra D&#8217;Or, Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution content-type="orgname">Universidade do Estado do Rio de Janeiro</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><label>Correspond&#234;ncia:</label><bold>Gl&#225;ucia Maria Moraes de Oliveira &#8226;</bold> Universidade Federal do Rio de Janeiro &#8211; R. Prof. Rodolpho P. Rocco, 255 &#8211; 8&#176; Andar &#8211; Sala 6. CEP <postal-code>21941-913</postal-code>, Cidade Universit&#225;ria, RJ &#8211; Brasil E-mail: <email>glauciamoraesoliveira@gmail.com</email> </corresp>
        <fn fn-type="conflict">
          <label>Potencial conflito de interesse</label>
          <p>N&#227;o h&#225; conflito com o presente artigo</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Editor respons&#225;vel pela revis&#227;o:</label>
          <p>Luis Beck da Silva</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>03</day>
        <month>10</month>
        <year>2025</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <year>2025</year>
      </pub-date>
      <volume>122</volume>
      <issue>9</issue>
      <elocation-id>e20240475</elocation-id>
      <history>
        <date date-type="received">
          <day>08</day>
          <month>07</month>
          <year>2024</year>
        </date>
        <date date-type="rev-recd">
          <day>24</day>
          <month>04</month>
          <year>2025</year>
        </date>
        <date date-type="accepted">
          <day>21</day>
          <month>05</month>
          <year>2025</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</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>A mortalidade por insufici&#234;ncia card&#237;aca (IC) pode ser subestimada quando considerada apenas a causa b&#225;sica nas declara&#231;&#245;es de &#243;bito (DO). A an&#225;lise das causas m&#250;ltiplas de &#243;bito permite uma avalia&#231;&#227;o mais abrangente dos fatores associados &#224; mortalidade.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Analisar as causas m&#250;ltiplas de &#243;bito hospitalar e tardio em pacientes com IC descompensada, de acordo com a fra&#231;&#227;o de eje&#231;&#227;o (FE) &#8212; reduzida (ICFEr), levemente reduzida (ICFElr) ou preservada (ICFEp).</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Estudo retrospectivo de uma coorte prospectiva composta por pacientes internados por IC descompensada em uma unidade cardiointensiva de um hospital privado. Foram avaliadas as causas m&#250;ltiplas de &#243;bito, tanto hospitalar quanto tardio. Adotou-se n&#237;vel de signific&#226;ncia de 5% para a an&#225;lise estat&#237;stica.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Foram inclu&#237;dos 519 pacientes, com m&#233;dia de idade de 74,87 &#177; 13,56 anos, sendo 57,6% do sexo masculino. As frequ&#234;ncias de ICFEp, ICFElr e ICFEr foram de 25,4%, 27% e 47,6%, respectivamente. As doen&#231;as cardiovasculares foram as principais causas de &#243;bito hospitalar e tardio nos tr&#234;s grupos, sem diferen&#231;a estat&#237;stica entre eles. As principais causas isoladas de morte, tanto hospitalar quanto tardia, foram septicemia (A41), IC (I50, I50.0, I50.9) e pneumonia (J12&#8211;J18). Na mortalidade tardia, observou-se diferen&#231;a estatisticamente significativa para septicemia e pneumonia. As doen&#231;as respirat&#243;rias cr&#244;nicas foram mais prevalentes entre os pacientes com FE mais reduzida (ICFEr e ICFElr). A an&#225;lise de correspond&#234;ncia revelou associa&#231;&#227;o entre causas circulat&#243;rias e ICFEr, causas neopl&#225;sicas e ICFEp, e causas end&#243;crino-metab&#243;licas e ICFElr.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>A an&#225;lise das causas m&#250;ltiplas de &#243;bito demonstra elevada incid&#234;ncia de mortes n&#227;o circulat&#243;rias em pacientes com IC descompensada, independentemente da FE, relacionadas sobretudo &#224; idade avan&#231;ada e &#224; presen&#231;a de comorbidades cr&#244;nicas.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Insufici&#234;ncia Card&#237;aca</kwd>
        <kwd>Mortalidade</kwd>
        <kwd>Causas de Morte</kwd>
      </kwd-group>
      <counts>
        <fig-count count="10"/>
        <table-count count="2"/>
        <equation-count count="0"/>
        <ref-count count="33"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <fig id="f1">
      <p>IC: insufici&#234;ncia card&#237;aca; ICFEr: insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o reduzida; ICFElr: insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o levemente reduzida; ICFEp: insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o preservada; FE: fra&#231;&#227;o de eje&#231;&#227;o; CID-10: Classifica&#231;&#227;o Internacional de Doen&#231;as, 10&#170; Revis&#227;o. *Agrupamento conforme os c&#243;digos alfanum&#233;ricos da CID-10.</p>
      <graphic xlink:href="1678-4170-abc-122-09-e20240475-40475-gf01.jpg"/></fig>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>A insufici&#234;ncia card&#237;aca (IC) &#233; uma s&#237;ndrome cl&#237;nica complexa e de natureza sist&#234;mica, caracterizada pela disfun&#231;&#227;o do cora&#231;&#227;o em fornecer fluxo sangu&#237;neo adequado para suprir as demandas metab&#243;licas dos tecidos.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Trata-se da terceira principal causa de morte por doen&#231;as cardiovasculares em pa&#237;ses desenvolvidos e de uma relevante causa de morbidade e hospitaliza&#231;&#245;es em todo o mundo.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Atualmente, a IC apresenta uma preval&#234;ncia global de 64,34 milh&#245;es de casos, correspondendo a 8,52 por 1.000 habitantes, com expressivo impacto em anos de vida saud&#225;vel perdidos por incapacidade (<italic>years of healthy life lost due to disability</italic>, YLDs). Nos &#250;ltimos anos, a preval&#234;ncia de IC aumentou 3,9% entre indiv&#237;duos com mais de 60 anos, consolidando-se como uma comorbidade de grande relev&#226;ncia nessa faixa et&#225;ria.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>Atualmente, a IC &#233; classificada de acordo com a fra&#231;&#227;o de eje&#231;&#227;o (FE) em tr&#234;s categorias: i) IC com FE reduzida (ICFEr), quando a FE &#233; &lt;40%; ii) IC com FE levemente reduzida (ICFElr), com FE entre 40% e 49%; e iii) IC com FE preservada (ICFEp), definida por FE &#8805;50%. Na classifica&#231;&#227;o anterior, a ICFElr era denominada IC com FE intermedi&#225;ria. Estudos demonstram que a ICFElr apresenta caracter&#237;sticas cl&#237;nicas, estruturais e funcionais intermedi&#225;rias entre a ICFEr e a ICFEp, o que fundamenta sua atual categoriza&#231;&#227;o. Este modelo &#233;, atualmente, o principal adotado pelas diretrizes para orientar as recomenda&#231;&#245;es terap&#234;uticas.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
      <p>A an&#225;lise isolada da causa b&#225;sica de morte pode subestimar de forma significativa a mortalidade associada a doen&#231;as cr&#244;nicas, como a IC. A avalia&#231;&#227;o das causas m&#250;ltiplas de &#243;bito constitui uma abordagem mais abrangente, permitindo identificar e correlacionar os determinantes envolvidos nos &#243;bitos relacionados a uma condi&#231;&#227;o espec&#237;fica.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
      <p>O objetivo deste estudo foi analisar as causas m&#250;ltiplas de &#243;bito, tanto hospitalar quanto tardio, em pacientes com IC classificados nos diferentes grupos de FE.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <sec>
        <title>Desenho do estudo</title>
        <p>Trata-se de uma an&#225;lise retrospectiva de um banco de dados coletado prospectivamente. Foram inclu&#237;dos pacientes admitidos na unidade cardiointensiva de um hospital privado, com 162 leitos, maiores de 18 anos, no per&#237;odo de setembro de 2011 a junho de 2019. O projeto foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa do Instituto D&#8217;Or de Pesquisa e Ensino (IDOR) sob parecer n&#186; 3.582.453, emitido em 18/09/2019 (CAAE: 18502319.3.0000.5249).</p>
      </sec>
      <sec>
        <title>Crit&#233;rios de elegibilidade</title>
        <p>Foram inclu&#237;dos pacientes internados por IC descompensada, com diagn&#243;stico estabelecido com base em crit&#233;rios cl&#237;nicos cl&#225;ssicos, como os crit&#233;rios de Framingham e Boston, al&#233;m de marcadores laboratoriais, como pept&#237;deo natriur&#233;tico tipo B (BNP) e fragmento N-terminal do pr&#243;-pept&#237;deo natriur&#233;tico tipo B (NT-proBNP). Foram exclu&#237;das 203 interna&#231;&#245;es m&#250;ltiplas, sendo considerado apenas o &#250;ltimo evento para cada paciente.</p>
      </sec>
      <sec>
        <title>Classifica&#231;&#227;o dos pacientes</title>
        <p>Os pacientes foram agrupados conforme a classifica&#231;&#227;o atual da IC, baseada na FE obtida na primeira ecocardiografia realizada durante a interna&#231;&#227;o: ICFEr (FE &lt;40%), ICFElr (FE 40%-49%), ICFEp (FE &#8805;50%).<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
      </sec>
      <sec>
        <title>Coleta de dados sobre &#243;bito</title>
        <p>A data de &#243;bito por todas as causas foi obtida no site da Corregedoria Geral da Justi&#231;a do Estado do Rio de Janeiro.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> As informa&#231;&#245;es sobre causas m&#250;ltiplas de &#243;bito foram extra&#237;das das DO fornecidas pela Secretaria Estadual de Sa&#250;de do Estado do Rio de Janeiro, por meio do Sistema de Informa&#231;&#227;o sobre Mortalidade.</p>
        <p>As causas declaradas de &#243;bito foram agrupadas de acordo com a FE dos pacientes. Para a an&#225;lise, todas as causas registradas nas DO foram consideradas, independentemente da linha ou da ordem de ocorr&#234;ncia. As causas foram organizadas conforme os cap&#237;tulos dos c&#243;digos alfanum&#233;ricos da Classifica&#231;&#227;o Internacional de Doen&#231;as, 10&#170; revis&#227;o (CID-10), visando a elabora&#231;&#227;o das tabelas de conting&#234;ncia e dos gr&#225;ficos descritivos.</p>
      </sec>
      <sec>
        <title>An&#225;lise estat&#237;stica</title>
        <p>A normalidade das vari&#225;veis cont&#237;nuas foi avaliada pelo teste de Kolmogorov-Smirnov. As vari&#225;veis cont&#237;nuas foram descritas como m&#233;dia &#177; desvio padr&#227;o, e as categ&#243;ricas, como n&#250;mero absoluto e percentual. A curva de Kaplan-Meier<sup><xref ref-type="bibr" rid="B8">8</xref></sup> foi utilizada para estimar a sobrevida ao longo do tempo, com compara&#231;&#245;es entre os grupos realizadas pelo teste de Tarone-Ware.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> As associa&#231;&#245;es entre as vari&#225;veis foram analisadas por meio do teste qui-quadrado de Pearson, aplicado nas tabelas e figuras.</p>
        <p>Adicionalmente, realizou-se uma an&#225;lise de correspond&#234;ncia para avaliar a rela&#231;&#227;o entre os grupos de FE e os grupos de patologias classificados segundo a CID-10. Os gr&#225;ficos fatoriais dessa an&#225;lise foram constru&#237;dos a partir das tabelas de conting&#234;ncia, que expressam a frequ&#234;ncia observada das causas de &#243;bito nos tr&#234;s grupos de IC. Essa abordagem permite representar, de forma gr&#225;fica, as associa&#231;&#245;es entre os grupos de FE e as m&#250;ltiplas causas de &#243;bito, tanto hospitalar quanto tardio, destacando a intera&#231;&#227;o entre as vari&#225;veis e os desfechos.</p>
        <p>As an&#225;lises foram conduzidas nos softwares IBM SPSS Statistics for Windows, vers&#227;o 28.0<sup><xref ref-type="bibr" rid="B10">10</xref></sup> e R.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> O n&#237;vel de signific&#226;ncia foi fixado em 5%.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>Foram inclu&#237;dos 519 pacientes, com m&#233;dia de idade de 74,87 &#177; 13,56 anos, dos quais 57,6% eram do sexo masculino. As distribui&#231;&#245;es dos pacientes nos grupos foram de 25,4% para ICFEp, 27% para ICFElr e 47,6% para ICFEr. O tempo m&#233;dio de seguimento foi de 2,94 &#177; 2,55 anos.</p>
      <p>Durante o per&#237;odo de acompanhamento, 52,3% dos pacientes evolu&#237;ram para &#243;bito, sendo 14,5% durante a hospitaliza&#231;&#227;o. N&#227;o foram observadas diferen&#231;as estatisticamente significativas entre os grupos de FE quanto &#224; mortalidade hospitalar.</p>
      <p>A <xref ref-type="table" rid="t1">Tabela 1</xref> apresenta as frequ&#234;ncias absolutas e relativas das causas de &#243;bito, agrupadas por sistemas org&#226;nicos, conforme os cap&#237;tulos da CID-10 e estratificadas pelos grupos de FE. As causas relacionadas ao aparelho circulat&#243;rio (I) foram as mais prevalentes, especialmente no grupo ICFEr, seguidas pelas doen&#231;as do aparelho respirat&#243;rio (J) e pelas causas infecciosas e mal definidas.</p>
      <table-wrap id="t1">
        <label>Tabela 1</label>
        <caption>
          <title>Causas de morte mencionadas em qualquer linha da declara&#231;&#227;o de &#243;bito, agrupadas por aparelho*, de acordo com a fra&#231;&#227;o de eje&#231;&#227;o de pacientes internados com diagn&#243;stico de insufici&#234;ncia card&#237;aca entre maio de 2011 e julho de 2019</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup width="16%">
            <col/>
            <col/>
            <col/>
            <col/>
            <col/>
            <col/>
          </colgroup>
          <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
            <tr style="background-color:#76B4CF;">
              <th align="left" valign="middle">Causas mencionadas por aparelhos (<xref ref-type="table-fn" rid="TFN1">*</xref>)</th>
              <th align="center" valign="middle">ICFEp (n, %)</th>
              <th align="center" valign="middle">ICFElr (n, %)</th>
              <th align="center" valign="middle">ICFEr (n, %)</th>
              <th align="center" valign="middle">Total de men&#231;&#245;es no DO (%)</th>
              <th align="center" valign="middle">Valor p</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="top">Aparelho circulat&#243;rio (I)</td>
              <td align="center" valign="top">77 (33,7%)</td>
              <td align="center" valign="top">81 (34,3%)</td>
              <td align="center" valign="top">193 (37,6%)</td>
              <td align="center" valign="top">351 (35,9%)</td>
              <td align="center" valign="top">0,50</td>
            </tr>
            <tr style="background-color:#C7DFEC;">
              <td align="left" valign="top">Aparelho respirat&#243;rio (J)</td>
              <td align="center" valign="top">32 (14%)</td>
              <td align="center" valign="top">38 (16,1%)</td>
              <td align="center" valign="top">62 (12,1%)</td>
              <td align="center" valign="top">132 (13,5%)</td>
              <td align="center" valign="top">0,31</td>
            </tr>
            <tr>
              <td align="left" valign="top">Infecciosas (A e B)</td>
              <td align="center" valign="top">23 (10,1%)</td>
              <td align="center" valign="top">33 (14%)</td>
              <td align="center" valign="top">59 (11,5%)</td>
              <td align="center" valign="top">115 (11,7%)</td>
              <td align="center" valign="top">0,41</td>
            </tr>
            <tr style="background-color:#C7DFEC;">
              <td align="left" valign="top">Mal definidas (R)</td>
              <td align="center" valign="top">21 (9,2%)</td>
              <td align="center" valign="top">21 (8,9%)</td>
              <td align="center" valign="top">58 (11,3%)</td>
              <td align="center" valign="top">100 (10,2%)</td>
              <td align="center" valign="top">0,50</td>
            </tr>
            <tr>
              <td align="left" valign="top">Aparelho geniturin&#225;rio (N)</td>
              <td align="center" valign="top">24 (10,5%)</td>
              <td align="center" valign="top">17 (7,2%)</td>
              <td align="center" valign="top">48 (9,4%)</td>
              <td align="center" valign="top">89 (9,1%)</td>
              <td align="center" valign="top">0,50</td>
            </tr>
            <tr style="background-color:#C7DFEC;">
              <td align="left" valign="top">Neoplasias (C e D)</td>
              <td align="center" valign="top">10 (4,4%)</td>
              <td align="center" valign="top">10 (4,3%)</td>
              <td align="center" valign="top">19 (3,7%)</td>
              <td align="center" valign="top">39 (4,0%)</td>
              <td align="center" valign="top">0,95</td>
            </tr>
            <tr>
              <td align="left" valign="top">End&#243;crinas, nutricionais e metab&#243;licas (E)</td>
              <td align="center" valign="top">9 (4%)</td>
              <td align="center" valign="top">12 (5%)</td>
              <td align="center" valign="top">15 (2,9%)</td>
              <td align="center" valign="top">36 (3,7%)</td>
              <td align="center" valign="top">0,34</td>
            </tr>
            <tr style="background-color:#C7DFEC;">
              <td align="left" valign="top">Sistema nervoso e cabe&#231;a (F, G e H)</td>
              <td align="center" valign="top">9 (4%)</td>
              <td align="center" valign="top">6 (2,5%)</td>
              <td align="center" valign="top">11 (2,1%)</td>
              <td align="center" valign="top">26 (2,6%)</td>
              <td align="center" valign="top">0,38</td>
            </tr>
            <tr>
              <td align="left" valign="top">Causas externas (V, X, W e Y)</td>
              <td align="center" valign="top">8 (3,5%)</td>
              <td align="center" valign="top">5 (2,1%)</td>
              <td align="center" valign="top">17 (3,3%)</td>
              <td align="center" valign="top">30 (3,1%)</td>
              <td align="center" valign="top">0,61</td>
            </tr>
            <tr style="background-color:#C7DFEC;">
              <td align="left" valign="top">Sistema osteomuscular e cut&#226;neo (L e M)</td>
              <td align="center" valign="top">2 (0,9%)</td>
              <td align="center" valign="top">3 (1,3%)</td>
              <td align="center" valign="top">2 (0,4%)</td>
              <td align="center" valign="top">7 (0,7%)</td>
              <td align="center" valign="top">0,39</td>
            </tr>
            <tr>
              <td align="left" valign="top">Outros grupamentos (K, P, O, S e T)</td>
              <td align="center" valign="top">13 (5,7%)</td>
              <td align="center" valign="top">10 (4,3%)</td>
              <td align="center" valign="top">29 (5,7%)</td>
              <td align="center" valign="top">52 (5,3%)</td>
              <td align="center" valign="top">0,69</td>
            </tr>
            <tr style="background-color:#C7DFEC;">
              <td align="left" valign="top">Total</td>
              <td align="center" valign="top">228 (100%)</td>
              <td align="center" valign="top">236 (100%)</td>
              <td align="center" valign="top">513 (100%)</td>
              <td align="center" valign="top">977 (100%)</td>
              <td align="center" valign="top">&#8212;</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <label>*</label>
            <p>Agrupamento conforme os c&#243;digos alfanum&#233;ricos da CID-10. Foi utilizado o teste qui-quadrado de Pearson. FE: fra&#231;&#227;o de eje&#231;&#227;o; IC: insufici&#234;ncia card&#237;aca; ICFEp: IC com FE preservada; ICFElr: IC com FE levemente reduzida; ICFEr: IC com FE reduzida.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Foram analisadas 266 DO, totalizando 977 men&#231;&#245;es de causas de &#243;bito. Houve uma perda de 7% dos dados devido &#224; aus&#234;ncia ou inconsist&#234;ncias nas DO.</p>
      <p>As causas de &#243;bito hospitalar, mencionadas em qualquer linha da DO, est&#227;o apresentadas na <xref ref-type="fig" rid="f2">Figura 1</xref>, agrupadas por condi&#231;&#245;es espec&#237;ficas, de acordo com a FE dos pacientes internados com diagn&#243;stico de IC entre maio de 2011 e julho de 2019.</p>
      <fig id="f2">
        <label>Figura 1</label>
        <caption>
          <title>Causas de morte hospitalar mencionadas em qualquer linha da declara&#231;&#227;o de &#243;bito, agrupadas por condi&#231;&#245;es espec&#237;ficas * de acordo com a fra&#231;&#227;o. Foi utilizado o teste qui-quadrado de Pearson. *Agrupamento por condi&#231;&#245;es espec&#237;ficas, conforme os c&#243;digos alfanum&#233;ricos da CID-10. FE: fra&#231;&#227;o de eje&#231;&#227;o; IC: insufici&#234;ncia card&#237;aca; ICFEp: IC com FE preservada; ICFElr: IC com FE levemente reduzida; ICFEr: IC com FE reduzida.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-122-09-e20240475-40475-gf02.jpg"/></fig>
      <p>A <xref ref-type="fig" rid="f3">Figura 2</xref> apresenta as causas de &#243;bito tardio, tamb&#233;m mencionadas em qualquer linha da DO e agrupadas por condi&#231;&#245;es espec&#237;ficas, segundo a FE dos pacientes inclu&#237;dos no mesmo per&#237;odo.</p>
      <fig id="f3">
        <label>Figura 2</label>
        <caption>
          <title>Causas de morte tardia, ap&#243;s a alta, mencionadas em qualquer linha da declara&#231;&#227;o de &#243;bito, com m&#233;dia do tempo de seguimento de 2,94 &#177; 2,55 anos agrupadas por condi&#231;&#245;es espec&#237;ficas,* de acordo com a fra&#231;&#227;o de eje&#231;&#227;o. Foi utilizado o teste qui-quadrado de Pearson. *Agrupamento por condi&#231;&#245;es espec&#237;ficas, conforme os c&#243;digos alfanum&#233;ricos da CID-10. FE: fra&#231;&#227;o de eje&#231;&#227;o; IC: insufici&#234;ncia card&#237;aca; ICFEp: IC com FE preservada; ICFElr: IC com FE levemente reduzida; ICFEr: IC com FE reduzida.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-122-09-e20240475-40475-gf03.jpg"/></fig>
      <p>A <xref ref-type="fig" rid="f4">Figura 3</xref> exibe a an&#225;lise de correspond&#234;ncia das causas de morte, agrupadas conforme os cap&#237;tulos da CID-10, da mesma forma que na <xref ref-type="table" rid="t1">Tabela 1</xref>. Observa-se, na an&#225;lise de correspond&#234;ncia, uma maior proximidade das causas relacionadas ao aparelho circulat&#243;rio (I) com o grupo ICFEr, das causas neopl&#225;sicas (C e D) com ICFEp, e das doen&#231;as end&#243;crino-metab&#243;licas (E) com ICFElr.</p>
      <fig id="f4">
        <label>Figura 3</label>
        <caption>
          <title>An&#225;lise de correspond&#234;ncia das causas de morte mencionadas em qualquer linha da declara&#231;&#227;o de &#243;bito, agrupadas por aparelho, de acordo com a fra&#231;&#227;o de eje&#231;&#227;o de pacientes internados com diagn&#243;stico de insufici&#234;ncia card&#237;aca entre maio de 2011 e julho de 2019. FE: fra&#231;&#227;o de eje&#231;&#227;o; IC: insufici&#234;ncia card&#237;aca; ICFEp: IC com FE preservada; ICFElr: IC com FE levemente reduzida; ICFEr: IC com FE reduzida.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-122-09-e20240475-40475-gf04.jpg"/></fig>
      <p>Na curva de sobrevida de Kaplan-Meier<sup><xref ref-type="bibr" rid="B7">7</xref></sup> (<xref ref-type="fig" rid="f5">Figura 4</xref>), n&#227;o foram identificadas diferen&#231;as estatisticamente significativas entre os grupos de IC.</p>
      <fig id="f5">
        <label>Figura 4</label>
        <caption>
          <title>Curva de sobrevida de Kaplan-Meier<sup><xref ref-type="bibr" rid="B8">8</xref></sup> dos pacientes com insufici&#234;ncia card&#237;aca durante todo o per&#237;odo de seguimento. FE: fra&#231;&#227;o de eje&#231;&#227;o; IC: insufici&#234;ncia card&#237;aca; ICFEp: IC com FE preservada; ICFElr: IC com FE levemente reduzida; ICFEr: IC com FE reduzida.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-122-09-e20240475-40475-gf05.jpg"/></fig>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>A mortalidade em pacientes com IC &#233; elevada e resulta de m&#250;ltiplos fatores, como a FE, a presen&#231;a de comorbidades e as causas espec&#237;ficas de &#243;bito.<sup><xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B13">13</xref></sup> No presente estudo, a classifica&#231;&#227;o dos pacientes segundo a FE n&#227;o demonstrou diferen&#231;as significativas nas taxas de mortalidade geral nem hospitalar em uma amostra com perfis cl&#237;nicos variados. Por outro lado, observou-se que as principais causas de morte variaram entre os grupos de FE, o que refor&#231;a a heterogeneidade cl&#237;nica e fisiopatol&#243;gica dos pacientes com IC. Embora as causas circulat&#243;rias tenham sido as mais frequentes, elas corresponderam a apenas cerca de um ter&#231;o dos &#243;bitos no grupo ICFEr. Entre os pacientes com ICFElr, destacaram-se as doen&#231;as respirat&#243;rias cr&#244;nicas como principais causas de morte. Al&#233;m disso, a septicemia foi a causa espec&#237;fica mais prevalente, tanto na mortalidade hospitalar quanto na tardia, com maior incid&#234;ncia nos pacientes com FE mais baixa. Esses achados ressaltam a relev&#226;ncia da an&#225;lise das causas m&#250;ltiplas de &#243;bito &#8212; uma abordagem pouco explorada na literatura &#8212;, capaz de revelar aspectos cruciais da trajet&#243;ria cl&#237;nica e do progn&#243;stico dos pacientes com IC.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
      <p>A considera&#231;&#227;o isolada da causa b&#225;sica de morte pode subestimar de forma relevante a mortalidade associada a doen&#231;as cr&#244;nicas, como a IC. A an&#225;lise das causas m&#250;ltiplas de &#243;bito, adotada neste estudo, representa uma abordagem mais abrangente para a avalia&#231;&#227;o da mortalidade, permitindo a identifica&#231;&#227;o e a associa&#231;&#227;o dos determinantes relacionados aos &#243;bitos em fun&#231;&#227;o de uma doen&#231;a espec&#237;fica.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Dessa forma, este estudo contribui para o aprimoramento do conhecimento sobre a epidemiologia das causas de morte em pacientes com IC, al&#233;m de fornecer subs&#237;dios para o desenvolvimento de estudos prospectivos que viabilizem a implementa&#231;&#227;o de estrat&#233;gias preventivas e terap&#234;uticas mais adequadas aos diferentes perfis de FE. Corroborando esses achados, uma revis&#227;o recente demonstrou que a morte cardiovascular &#8212; especialmente a morte s&#250;bita e aquela relacionada diretamente &#224; IC &#8212; foi respons&#225;vel por mais da metade dos &#243;bitos em pacientes com ICFEp, e por uma propor&#231;&#227;o ainda maior naqueles com FE abaixo da faixa normal. Contudo, as causas n&#227;o cardiovasculares continuam representando um componente expressivo da mortalidade nessa popula&#231;&#227;o.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
      <p>A ICFEp &#233; frequentemente associada a comorbidades cr&#244;nicas n&#227;o card&#237;acas, que impactam diretamente na fisiopatologia e no progn&#243;stico da s&#237;ndrome.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> Um achado relevante deste estudo foi a associa&#231;&#227;o entre ICFEp e neoplasias, identificada na an&#225;lise de correspond&#234;ncia. Esse resultado pode estar relacionado &#224; elevada m&#233;dia de idade da amostra. A idade avan&#231;ada, reconhecida como mais prevalente no grupo ICFEp em compara&#231;&#227;o ao ICFEr, tem sido consistentemente confirmada em estudos epidemiol&#243;gicos.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> Dados recentes indicam que indiv&#237;duos que desenvolvem ICFEp possuem, em m&#233;dia, cerca de 6 anos a mais do que aqueles que desenvolvem ICFEr,<sup><xref ref-type="bibr" rid="B17">17</xref></sup> al&#233;m de a ICFEp representar uma propor&#231;&#227;o crescente dos casos incidentes de IC em pessoas idosas.</p>
      <p>Entre os pacientes com IC, aproximadamente 10% a 25% apresentam ICFElr. Evid&#234;ncias recentes indicam que esses indiv&#237;duos apresentam um progn&#243;stico intermedi&#225;rio entre ICFEr e ICFEp. A ICFElr est&#225; frequentemente associada a comorbidades cr&#244;nicas n&#227;o card&#237;acas, como hipertens&#227;o arterial, diabetes melito, doen&#231;a renal cr&#244;nica e anemia, que podem impactar negativamente os desfechos cl&#237;nicos.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Al&#233;m disso, observou-se uma forte associa&#231;&#227;o entre ICFElr e doen&#231;as respirat&#243;rias cr&#244;nicas, como asma e doen&#231;a pulmonar obstrutiva cr&#244;nica, que foram significativamente mais prevalentes nesse grupo na presente amostra. A an&#225;lise de correspond&#234;ncia tamb&#233;m evidenciou uma rela&#231;&#227;o entre ICFElr e doen&#231;as end&#243;crino-metab&#243;licas, especialmente o diabetes melito.</p>
      <p>Pacientes com ICFEr apresentam elevado risco de morte por causas cardiovasculares, como infarto agudo do mioc&#225;rdio, arritmias e choque cardiog&#234;nico.<sup><xref ref-type="bibr" rid="B13">13</xref>,<xref ref-type="bibr" rid="B18">18</xref></sup> Nesta amostra, as causas cardiovasculares representaram aproximadamente 36% das men&#231;&#245;es nas DO, sendo mais frequentes no grupo ICFEr, com cerca de 20% das men&#231;&#245;es. Por&#233;m, causas n&#227;o cardiovasculares tamb&#233;m tiveram participa&#231;&#227;o expressiva, destacando-se as doen&#231;as respirat&#243;rias (J) com 13,5%, as infec&#231;&#245;es (A e B) com 11,8% e as neoplasias (C e D) com 4%, totalizando aproximadamente 30% das causas mencionadas. Esse resultado difere dos dados da literatura nacional, que apontam que cerca de 50% dos &#243;bitos em pacientes com IC est&#227;o relacionados ao aparelho circulat&#243;rio (I) e 25% ao respirat&#243;rio (J),<sup><xref ref-type="bibr" rid="B9">9</xref></sup> o que pode justificar a elevada mortalidade observada nesta amostra. Os grupos ICFEp e ICFElr tamb&#233;m apresentaram propor&#231;&#245;es relevantes de causas cardiovasculares, correspondendo a 7,9% e 8,3%, respectivamente. No entanto, ambos os grupos apresentaram participa&#231;&#227;o expressiva de causas n&#227;o cardiovasculares, como infec&#231;&#245;es (2,4% e 3,4%) e neoplasias (1,0% em ambos os grupos). No grupo ICFEr, manteve-se o predom&#237;nio de causas relacionadas ao aparelho circulat&#243;rio, com 19,8% das men&#231;&#245;es. Esses achados est&#227;o em conson&#226;ncia com a literatura recente, que reconhece a septicemia como um fator de risco independente para mortalidade em pacientes com IC, especialmente naqueles com disfun&#231;&#227;o sist&#243;lica.<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
      <p>A elevada frequ&#234;ncia de causas infecciosas, tanto nos &#243;bitos hospitalares quanto nos tardios, &#233; um dado de grande relev&#226;ncia no contexto deste estudo, configurando-se, inclusive, como a causa mais prevalente de morte na amostra analisada. Corroborando esse achado, um estudo multic&#234;ntrico franc&#234;s com 581 pacientes internados em unidades de terapia intensiva por IC aguda identificou uma taxa de infec&#231;&#227;o de 20% durante a hospitaliza&#231;&#227;o.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
      <p>A faixa et&#225;ria a partir de 60 anos &#8212; pr&#243;xima da idade m&#237;nima da amostra deste estudo &#8212;, associada &#224; presen&#231;a de processos infecciosos, contribui para o aumento da morbidade e da mortalidade desses pacientes quando comparados a indiv&#237;duos mais jovens.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup> Em um estudo franc&#234;s multic&#234;ntrico com 4.252 pacientes adultos, 429 desenvolveram infec&#231;&#227;o hospitalar. A ocorr&#234;ncia desse desfecho esteve independentemente associada &#224; presen&#231;a de comorbidades, neoplasias, neutropenia, uso pr&#233;vio de antimicrobianos, interna&#231;&#227;o em unidade de terapia intensiva, transfer&#234;ncia de outro hospital, intuba&#231;&#227;o traqueal por mais de 24 horas e tempo prolongado de hospitaliza&#231;&#227;o.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> Al&#233;m disso, em pacientes idosos, a necessidade frequente de interna&#231;&#227;o para manejo de suas condi&#231;&#245;es cl&#237;nicas &#233; agravada pela alta letalidade das infec&#231;&#245;es adquiridas no ambiente hospitalar, o que torna esse fator particularmente relevante nessa popula&#231;&#227;o.<sup><xref ref-type="bibr" rid="B21">21</xref></sup></p>
      <p>Neste contexto, a idade avan&#231;ada da amostra tamb&#233;m influencia os padr&#245;es de ocorr&#234;ncia dos &#243;bitos relacionados ao aparelho circulat&#243;rio. Nos agrupamentos por condi&#231;&#245;es espec&#237;ficas, observa-se que a IC (I50), que apresentou a maior propor&#231;&#227;o em um estudo brasileiro, com frequ&#234;ncia de 23,26%,<sup><xref ref-type="bibr" rid="B5">5</xref></sup> n&#227;o foi a men&#231;&#227;o mais frequente nas DO desta amostra. No &#226;mbito hospitalar, destacou-se uma maior propor&#231;&#227;o de men&#231;&#245;es a IC (I50) no grupo ICFElr em compara&#231;&#227;o ao grupo ICFEp. Al&#233;m disso, observou-se um gradiente nas men&#231;&#245;es por IC (I50), por causas infecciosas e por doen&#231;as isqu&#234;micas &#8212; tanto agudas quanto cr&#244;nicas &#8212;, com varia&#231;&#245;es nas frequ&#234;ncias entre os grupos ICFEr, ICFElr e ICFEp, respectivamente. A presen&#231;a recorrente dessas causas de morte refor&#231;a que o risco de mortalidade permanece elevado entre 12 e 18 meses ap&#243;s a hospitaliza&#231;&#227;o por IC.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> Adicionalmente, as taxas de readmiss&#227;o por IC em adultos jovens s&#227;o semelhantes &#224;s observadas em idosos, o que indica que o risco de reinterna&#231;&#227;o persiste independentemente da faixa et&#225;ria.<sup><xref ref-type="bibr" rid="B24">24</xref></sup></p>
      <p>A idade avan&#231;ada tamb&#233;m foi reconhecida como mais frequente no grupo ICFEp em compara&#231;&#227;o ao ICFEr, achado que tem sido consistentemente confirmado em diversos estudos epidemiol&#243;gicos sobre ICFEp.<sup><xref ref-type="bibr" rid="B16">16</xref></sup></p>
      <p>Desde o s&#233;culo XX, observou-se um expressivo aumento da longevidade mundial, impulsionado principalmente pelo controle das doen&#231;as transmiss&#237;veis e pelo avan&#231;o das medidas sanit&#225;rias. Como consequ&#234;ncia, houve um crescimento significativo na preval&#234;ncia de doen&#231;as cr&#244;nicas. No entanto, esse aumento da expectativa de vida &#233; atenuado pelo envelhecimento e pelo crescimento populacional, resultando em eleva&#231;&#227;o real das taxas de mortalidade por doen&#231;as cardiovasculares, associadas ao avan&#231;o da idade, ao maior consumo de tabaco e &#224; ado&#231;&#227;o de dietas aterog&#234;nicas. Apesar desse cen&#225;rio, observa-se, nas &#250;ltimas d&#233;cadas, uma redu&#231;&#227;o das mortes por doen&#231;as cardiovasculares, atribu&#237;da ao avan&#231;o dos tratamentos espec&#237;ficos, o que tem contribu&#237;do para o prolongamento adicional da expectativa de vida.<sup><xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup> A IC &#233; uma condi&#231;&#227;o altamente prevalente, com incid&#234;ncia crescente, tendo como um dos principais fatores contribuintes o envelhecimento populacional. Dados epidemiol&#243;gicos confirmam essa tend&#234;ncia e identificam a idade &gt;65 anos como um fator predisponente para o desenvolvimento de IC.<sup><xref ref-type="bibr" rid="B27">27</xref>-<xref ref-type="bibr" rid="B33">33</xref></sup></p>
      <p>Em publica&#231;&#227;o anterior, utilizando a mesma amostra, observou-se que n&#227;o houve diferen&#231;a estatisticamente significativa na mortalidade entre os grupos de FE durante o seguimento de 2,94 &#177; 2,55 anos. Da mesma forma, a an&#225;lise pela curva de sobrevida n&#227;o identificou diferen&#231;as entre ICFEp e ICFElr, nem entre ICFEp e ICFEr, sendo observada apenas diferen&#231;a significativa entre ICFElr e ICFEr (<xref ref-type="fig" rid="f5">Figura 4</xref>). Nesse estudo pr&#233;vio, a hip&#243;tese de que a categoriza&#231;&#227;o da FE seria uma vari&#225;vel preditora de mortalidade hospitalar e tardia n&#227;o foi confirmada, mesmo ap&#243;s a aplica&#231;&#227;o de modelos de <italic>machine learning</italic>. Ressalta-se que, na ocasi&#227;o, as m&#250;ltiplas causas de morte dessa popula&#231;&#227;o n&#227;o foram analisadas, sendo objeto de investiga&#231;&#227;o do presente estudo.<sup><xref ref-type="bibr" rid="B33">33</xref></sup></p>
      <p>As principais limita&#231;&#245;es deste estudo est&#227;o relacionadas &#224; qualidade do preenchimento das DO, o que pode impactar a precis&#227;o das informa&#231;&#245;es sobre as causas de morte. Outra limita&#231;&#227;o relevante foi a n&#227;o localiza&#231;&#227;o de 21 DO da amostra, o que impossibilitou uma an&#225;lise completamente abrangente. No entanto, foram obtidos dados de 266 DO (93% da amostra), totalizando 977 men&#231;&#245;es de causas de &#243;bito. Esse quantitativo foi considerado suficiente e n&#227;o comprometeu a interpreta&#231;&#227;o cl&#237;nica dos resultados.</p>
      <p>Este estudo contribui para uma compreens&#227;o mais abrangente dos m&#250;ltiplos fatores associados &#224; IC, especialmente no que se refere &#224; rela&#231;&#227;o entre a FE e as doen&#231;as cr&#244;nicas relacionadas ao envelhecimento. At&#233; o momento, n&#227;o foram identificados estudos que correlacionem mortalidade por m&#250;ltiplas causas com os diferentes perfis de FE. A abordagem adotada permitiu aprofundar a compreens&#227;o dos mecanismos subjacentes &#224; IC e &#224;s comorbidades associadas, al&#233;m de gerar hip&#243;teses que podem orientar o desenvolvimento de estrat&#233;gias terap&#234;uticas e de preven&#231;&#227;o direcionadas &#224; redu&#231;&#227;o da morbidade e da mortalidade nessa popula&#231;&#227;o.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>Este estudo destaca a relev&#226;ncia da an&#225;lise das causas m&#250;ltiplas de &#243;bito, capaz de revelar aspectos importantes da evolu&#231;&#227;o cl&#237;nica e do progn&#243;stico de pacientes com IC, os quais n&#227;o s&#227;o captados pela an&#225;lise isolada da causa b&#225;sica de morte. Na amostra analisada, observou-se uma alta incid&#234;ncia de causas de morte &#8212; tanto hospitalares quanto tardias &#8212; n&#227;o relacionadas ao aparelho circulat&#243;rio, em pacientes internados por IC descompensada, independentemente da classifica&#231;&#227;o em ICFEr, ICFElr ou ICFEp. Esses desfechos parecem estar mais associados &#224; idade avan&#231;ada e &#224; presen&#231;a de comorbidades cr&#244;nicas do que propriamente &#224; s&#237;ndrome da IC. Esses achados refor&#231;am a necessidade de estudos prospectivos para confirmar os resultados e para subsidiar o desenvolvimento de estrat&#233;gias de manejo mais adequadas e personalizadas, considerando os diferentes fen&#243;tipos de IC.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure" id="fn1">
        <label>Fontes de financiamento</label>
        <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
      </fn>
      <fn fn-type="other" id="fn2">
        <label>Vincula&#231;&#227;o acad&#234;mica</label>
        <p>Este artigo &#233; parte de disserta&#231;&#227;o de mestrado de Giovanni Possamai Dutra pela Universidade Federal do Rio de Janeiro.</p>
      </fn>
      <fn fn-type="other" id="fn3">
        <label>Aprova&#231;&#227;o &#233;tica e consentimento informado</label>
        <p>Este estudo foi aprovado pelo Comit&#234; de &#201;tica do Instituto D&#180;Or de Ensino e Pesquisa sob o n&#250;mero de protocolo 3582453. Todos os procedimentos envolvidos nesse estudo est&#227;o de acordo com a Declara&#231;&#227;o de Helsinki de 1975, atualizada em 2013.</p>
      </fn>
      <fn fn-type="other" id="fn4">
        <label>Uso de Intelig&#234;ncia Artificial</label>
        <p>Os autores n&#227;o utilizaram ferramentas de intelig&#234;ncia artificial no desenvolvimento deste trabalho.</p>
      </fn>
    </fn-group>
    <sec sec-type="data-availability" specific-use="data-in-article">
      <label>Disponibilidade de Dados</label>
      <p>Os conte&#250;dos subjacentes ao texto da pesquisa est&#227;o contidos no manuscrito.</p>
    </sec>
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          <source>J Intern Med</source>
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    <app-group>
      <app id="app1">
        <label>*Material suplementar</label>
        <p>Para informa&#231;&#227;o adicional, por favor, <ext-link ext-link-type="uri" xlink:href="http://abccardiol.org/supplementary-material/2025/12209/2024-0475_AO_material-suplementar.pdf">clique aqui</ext-link>.</p>
      </app>
    </app-group>
  </back>
  <sub-article article-type="translation" id="S1" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20240475i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Analysis of Mortality from Multiple Causes in Heart Failure Categorized by Ejection Fraction</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7668-4224</contrib-id>
          <name>
            <surname>Dutra</surname>
            <given-names>Giovanni Possamai</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7443-7270</contrib-id>
          <name>
            <surname>Gomes</surname>
            <given-names>Bruno Ferraz de Oliveira</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6799-7111</contrib-id>
          <name>
            <surname>Silva</surname>
            <given-names>Thiago Moreira Bastos da</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Peres</surname>
            <given-names>Leticia Souza</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rangel</surname>
            <given-names>Marco Ant&#244;nio Netto Armando</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Petriz</surname>
            <given-names>Jo&#227;o Luiz Fernandes</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Carmo</surname>
            <given-names>Plinio Resende do</given-names>
            <suffix>Junior</suffix>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nascimento</surname>
            <given-names>Emilia Matos</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff6">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pereira</surname>
            <given-names>Basilio de Bragan&#231;a</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-0737-6188</contrib-id>
          <name>
            <surname>Oliveira</surname>
            <given-names>Gl&#225;ucia Maria Moraes de</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff4">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff5">
          <label>2</label>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital Barra D&#8217;Or, Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff6">
          <label>3</label>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><label>Mailing Address:</label><bold>Gl&#225;ucia Maria Moraes de Oliveira &#8226;</bold> Universidade Federal do Rio de Janeiro &#8211; R. Prof. Rodolpho P. Rocco, 255 &#8211; 8&#176; Andar &#8211; Sala 6. CEP <postal-code>21941-913</postal-code>, Cidade Universit&#225;ria, RJ &#8211; Brazil E-mail: <email>glauciamoraesoliveira@gmail.com</email> </corresp>
        <fn fn-type="conflict">
          <label>Potential conflict of interest</label>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Editor responsible for the review:</label>
          <p>Luis Beck da Silva</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Mortality in heart failure (HF) may be underestimated when analyses rely solely on the underlying cause of death from death certificates (DCs), whereas including multiple causes of death enables a broader examination of mortality and its determinants.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To analyze the multiple causes of in-hospital and late death in patients with decompensated HF and reduced ejection fraction (EF) (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF).</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>Retrospective analysis of a prospective cohort of patients admitted for decompensated HF to a cardiac intensive care unit at a private hospital. The analysis included multiple causes of in-hospital and late deaths. A significance level of 5% was adopted.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>The analysis included 519 individuals with a mean age of 74.87 &#177; 13.56 years, of whom 57.6% were male. The distribution of HFpEF, HFmrEF, and HFrEF was 25.4%, 27%, and 47.6%, respectively. Cardiovascular diseases (I) were the main causes of in-hospital and late death across all three EF groups, with no significant differences among them. The primary isolated causes of in-hospital and late death were septicemia (A41), HF (I50, I50.0, I50.9), and pneumonia (J12-J18). In late death, septicemia and pneumonia showed significant differences among the groups. Chronic respiratory causes were more frequent in patients with lower EF (HFrEF and HFmrEF). Correspondence analysis revealed an association between circulatory causes and HFrEF, neoplastic causes and HFpEF, and endocrine and metabolic causes and HFmrEF.</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>The analysis of multiple causes of death reveals a high rate of non-circulatory deaths in patients with decompensated HF, regardless of EF, linked to age and chronic comorbidities.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Heart Failure</kwd>
        <kwd>Mortality</kwd>
        <kwd>Cause of Death</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Heart failure (HF) is a complex, systemic clinical syndrome defined as a cardiac dysfunction that causes an inadequate blood supply to meet the metabolic needs of tissues.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> It is the third leading cause of death from cardiovascular disease in developed countries and an important cause of morbidity and hospitalization worldwide.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> The global prevalence of HF currently stands at 64.34 million cases (8.52 per 1,000 inhabitants), significantly contributing to years of healthy life lost due to disability (YLDs). In recent years, the prevalence of HF has increased by 3.9% in patients older than 60 years of age, representing an important comorbidity in this age group.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>Currently, HF is classified based on EF into HF with reduced EF (HFrEF; EF &lt; 40%), HF with mildly reduced EF (HFmrEF; EF between 40% and 49%), and HF with preserved EF (HFpEF; EF &#8805; 50%). In a previous classification, HFmrEF was called HF with intermediate EF. Studies confirm that HFmrEF has characteristics that are intermediate between HFrEF and HFpEF, justifying the new categorization. This model has become the primary framework used by guidelines to provide treatment recommendations.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
        <p>Analyzing only the underlying cause of death can significantly underestimate mortality related to chronic diseases like HF. Including multiple causes of death provides a more comprehensive approach to evaluating mortality, allowing for a better correlation between the determinants associated with deaths caused by a specific condition.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
        <fig id="f6">
          <p>EF: ejection fraction; HF: heart failure; HFmrEF: HF with mildly reduced EF; HFpEF: HF with preserved EF; HFrEF: HF with reduced EF; ICD-10: International Classification of Diseases, 10<sup>th</sup> Revision. *Grouping according to ICD-10 alphanumeric codes.</p>
          <graphic xlink:href="1678-4170-abc-122-09-e20240475-40475-gf01-en.jpg"/></fig>
        <p>The aim of this study was to analyze the multiple causes of in-hospital and late deaths in patients with HF classified by different EF groups.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <p>This was a retrospective analysis of a prospectively collected database. The study included patients admitted to the cardiac intensive care unit of a 162-bed private hospital, aged 18 years or older, between September 2011 and June 2019. The HF diagnosis on admission was based on classical clinical criteria, including the Framingham and Boston criteria, along with laboratory criteria such as BNP and NT-pro-BNP levels. The patients were grouped according to the current HF classification, <italic>i.e.,</italic> HFrEF, HFmrEF, and HFpEF, based on the first echocardiogram obtained during hospitalization.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> In patients with more than one recorded event, only the most recent hospitalization was considered. Thus, 203 multiple hospitalizations were excluded, with only the last hospitalization being considered. The date of death from all causes was collected from the website of the General Internal Affairs Office of the Court of Justice of the State of Rio de Janeiro.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> The data on mortality from multiple causes were collected from death certificates (DCs) provided by the State Health Department of Rio de Janeiro (SES-RJ) through the Mortality Information System (SIM). The occurrences of the reported causes of death were grouped according to EF. Multiple causes of death were considered&#8212;regardless of the line on which they were recorded on the DC or their order of occurrence&#8212;for constructing the contingency table and graphs. The causes were categorized based on the chapter groupings defined by the alphanumeric codes of the International Classification of Diseases, 10th Revision (ICD-10)</p>
        <p>The project was submitted to the Research Ethics Committee of the <italic>Instituto D&#8217;Or de Ensino e Pesquisa</italic> (IDOR) and received approval based on the opinion issued on September 18, 2019, with ethics assessment number 18502319.3.0000.5249 (Opinion: 3.582.453).</p>
        <sec>
          <title>Statistical analysis</title>
          <p>The normality of quantitative variables was assessed using the Kolmogorov-Smirnov test. The results were displayed as mean &#177; standard deviation (continuous variables) or number of occurrences and percentage (categorical variables). A Kaplan-Meier curve<sup><xref ref-type="bibr" rid="B8">8</xref></sup> was used to analyze survival over time, with the Tarone-Ware test<sup><xref ref-type="bibr" rid="B9">9</xref></sup> applied for group comparisons. Pearson's chi-square test was performed to verify the associations shown in the tables and figures. The analyses were performed using SPSS and R software.<sup><xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B11">11</xref></sup> A significance level of 5% was adopted.</p>
          <p>A correspondence analysis was performed with the EF groups of HF and the pathology groups derived from the ICD-10. The factor plots from the correspondence analysis were constructed based on contingency tables, which show the observed frequency of causes of death across the three HF groups. The visual representation through correspondence factor analysis graphically displays the relationship between the variables of interest, such as EF classes, and their outcomes, including multiple causes of in-hospital and late death, illustrating how these variables relate to the outcomes.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>The analysis included 519 individuals with a mean age of 74.87 &#177; 13.56 years, of whom 57.6% were male. The frequency distributions of the HFpEF, HFmrEF, and HFrEF groups were 25.4%, 27%, and 47.6%, respectively. The mean follow-up duration was 2.94 &#177; 2.55 years. During the follow-up period, 52.3% of the patients died, with 14.5% of them dying during hospitalization, without a significant difference among the groups.</p>
        <p><xref ref-type="table" rid="t2">Table 1</xref> displays the absolute and relative frequencies of causes of death grouped by system and organized by EF. Causes related to the circulatory system (I) were the most frequent, especially in the HFrEF group, followed by those related to the respiratory system (J), and infectious and ill-defined causes. The data were collected from 266 death certificates, with a total of 977 entries. There was a 7% data loss from the DCs.</p>
        <table-wrap id="t2">
          <label>Table 1</label>
          <caption>
            <title>Causes of death recorded in any line of the death certificate, grouped by system* and organized according to ejection fraction, among patients hospitalized with a diagnosis of HF between May 2011 and July 2019</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="16%">
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr style="background-color:#76B4CF;">
                <th align="left" valign="middle">Causes reported by systems (<xref ref-type="table-fn" rid="TFN2">*</xref>)</th>
                <th align="center" valign="middle">HFpEF (n, %)</th>
                <th align="center" valign="middle">HFmrEF (n, %)</th>
                <th align="center" valign="middle">HFrEF (n, %)</th>
                <th align="center" valign="middle">TOTAL (%)</th>
                <th align="center" valign="middle">p</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="top">Circulatory system (I)</td>
                <td align="center" valign="top">77 (33.7%)</td>
                <td align="center" valign="top">81 (34.3%)</td>
                <td align="center" valign="top">193 (37.6%)</td>
                <td align="center" valign="top">351 (35.9%)</td>
                <td align="center" valign="top">0.50</td>
              </tr>
              <tr>
                <td align="left" valign="top">Respiratory system (J)</td>
                <td align="center" valign="top">32 (14%)</td>
                <td align="center" valign="top">38 (16.1%)</td>
                <td align="center" valign="top">62 (12.1%)</td>
                <td align="center" valign="top">132 (13.5%)</td>
                <td align="center" valign="top">0.31</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="top">Infectious (A and B)</td>
                <td align="center" valign="top">23 (10.1%)</td>
                <td align="center" valign="top">33 (14%)</td>
                <td align="center" valign="top">59 (11.5%)</td>
                <td align="center" valign="top">115 (11.7%)</td>
                <td align="center" valign="top">0.41</td>
              </tr>
              <tr>
                <td align="left" valign="top">Ill-defined (R)</td>
                <td align="center" valign="top">21 (9.2%)</td>
                <td align="center" valign="top">21 (8.9%)</td>
                <td align="center" valign="top">58 (11.3%)</td>
                <td align="center" valign="top">100 (10.2%)</td>
                <td align="center" valign="top">0.50</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="top">Genitourinary system (N)</td>
                <td align="center" valign="top">24 (10.5%)</td>
                <td align="center" valign="top">17 (7.2%)</td>
                <td align="center" valign="top">48 (9.4%)</td>
                <td align="center" valign="top">89 (9.1%)</td>
                <td align="center" valign="top">0.50</td>
              </tr>
              <tr>
                <td align="left" valign="top">Neoplasms (C and D)</td>
                <td align="center" valign="top">10 (4.4%)</td>
                <td align="center" valign="top">10 (4.3%)</td>
                <td align="center" valign="top">19 (3.7%)</td>
                <td align="center" valign="top">39 (4.0%)</td>
                <td align="center" valign="top">0.95</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="top">Endocrine, nutritional, and metabolic (E)</td>
                <td align="center" valign="top">9 (4%)</td>
                <td align="center" valign="top">12 (5%)</td>
                <td align="center" valign="top">15 (2.9%)</td>
                <td align="center" valign="top">36 (3.7%)</td>
                <td align="center" valign="top">0.34</td>
              </tr>
              <tr>
                <td align="left" valign="top">Nervous system and head (F, G, and H)</td>
                <td align="center" valign="top">9 (4%)</td>
                <td align="center" valign="top">6 (2.5%)</td>
                <td align="center" valign="top">11 (2.1%)</td>
                <td align="center" valign="top">26 (2.6%)</td>
                <td align="center" valign="top">0.38</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="top">External causes (V, X, W, and Y)</td>
                <td align="center" valign="top">8 (3.5%)</td>
                <td align="center" valign="top">5 (2.1%)</td>
                <td align="center" valign="top">17 (3.3%)</td>
                <td align="center" valign="top">30 (3.1%)</td>
                <td align="center" valign="top">0.61</td>
              </tr>
              <tr>
                <td align="left" valign="top">Musculoskeletal and cutaneous system (L and M)</td>
                <td align="center" valign="top">2 (0.9%)</td>
                <td align="center" valign="top">3 (1.3%)</td>
                <td align="center" valign="top">2 (0.4%)</td>
                <td align="center" valign="top">7 (0.7%)</td>
                <td align="center" valign="top">0.39</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="top">Other groups (K, P, O, S, and T)</td>
                <td align="center" valign="top">13 (5.7%)</td>
                <td align="center" valign="top">10 (4.3%)</td>
                <td align="center" valign="top">29 (5.7%)</td>
                <td align="center" valign="top">52 (5.3%)</td>
                <td align="center" valign="top">0.69</td>
              </tr>
              <tr>
                <td align="left" valign="top">Total</td>
                <td align="center" valign="top">228 (100%)</td>
                <td align="center" valign="top">236 (100%)</td>
                <td align="center" valign="top">513 (100%)</td>
                <td align="center" valign="top">977 (100%)</td>
                <td align="center" valign="top">-</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <label>*</label>
              <p>Groups according to the ICD-10 alphanumeric codes. Pearson's chi-square test was applied. EF: ejection fraction; HF; heart failure; HFpEF: heart failure with preserved ejection fraction; HFmrEF: heart failure with mildly reduced ejection fraction; HFrEF: heart failure with reduced ejection fraction.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>*Groups according to the ICD-10 alphanumeric codes. Pearson's chi-square test was applied. EF: ejection fraction; HF; heart failure; HFpEF: heart failure with preserved ejection fraction; HFmrEF: heart failure with mildly reduced ejection fraction; HFrEF: heart failure with reduced ejection fraction.</p>
        <p><xref ref-type="fig" rid="f7">Figure 1</xref> shows the causes of in-hospital deaths listed in any line of the DC, grouped by specific conditions and organized according to EF in patients admitted with a diagnosis of HF between May 2011 and July 2019.</p>
        <fig id="f7">
          <label>Figure 1</label>
          <caption>
            <title>Causes of in-hospital death mentioned on any line of the death certificate, grouped by specific conditions* according to the fraction. Pearson's chi-square test was used. *Grouping by specific conditions, according to ICD-10 alphanumeric codes. EF: ejection fraction; HF: heart failure; HFpEF: heart failure with preserved ejection fraction; HFmrEF: heart failure with mildly reduced ejection fraction; HFrEF: heart failure with reduced ejection fraction.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-122-09-e20240475-40475-gf02-en.jpg"/></fig>
        <p><xref ref-type="fig" rid="f8">Figure 2</xref> shows the causes of late deaths listed in any line of the DC, grouped by specific conditions and organized according to EF in patients admitted with a diagnosis of HF between May 2011 and July 2019.</p>
        <fig id="f8">
          <label>Figure 2</label>
          <caption>
            <title>Causes of late death after discharge, listed in any line of the death certificate, during a mean follow-up of 2.94 &#177; 2.55 years, grouped by specific conditions* and organized according to ejection fraction. Pearson's chi-square test was applied. EF: ejection fraction; HF: heart failure; HFpEF: heart failure with preserved ejection fraction; HFmrEF: heart failure with mildly reduced ejection fraction; HFrEF: heart failure with reduced ejection fraction.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-122-09-e20240475-40475-gf03-en.jpg"/></fig>
        <p><xref ref-type="fig" rid="f9">Figure 3</xref> illustrates the correspondence analysis of the causes of death grouped according to ICD-10 alphanumeric code by system, as in <xref ref-type="table" rid="t2">Table 1</xref>. In the correspondence analysis, a proximity was observed between circulatory system causes (I) and HFrEF, between neoplastic causes (C and D) and HFpEF, and between endocrine and metabolic causes (E) and HFmrEF.</p>
        <fig id="f9">
          <label>Figure 3</label>
          <caption>
            <title>Correspondence analysis of the causes of death mentioned in any line of the death certificate, grouped by system (according to ICD-10 alphanumeric codes) and organized according to ejection fraction in patients hospitalized with a diagnosis of HF between May 2011 and July 2019. HFpEF: heart failure with preserved ejection fraction; HFmrEF: heart failure with mildly reduced ejection fraction; HFrEF: heart failure with reduced ejection fraction.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-122-09-e20240475-40475-gf04-en.jpg"/></fig>
        <p>In the Kaplan-Meier survival curve <sup><xref ref-type="bibr" rid="B7">7</xref></sup> (<xref ref-type="fig" rid="f10">Figure 4</xref>), no difference was observed among the HF groups.</p>
        <fig id="f10">
          <label>Figure 4</label>
          <caption>
            <title>Survival (Kaplan-Meier curve<sup><xref ref-type="bibr" rid="B8">8</xref></sup>) of patients with HF throughout the follow-up period. HFpEF: heart failure with preserved ejection fraction; HFmrEF: heart failure with mildly reduced ejection fraction; HFrEF: heart failure with reduced ejection fraction.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-122-09-e20240475-40475-gf05-en.jpg"/></fig>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>The mortality among patients with HF is high and depends on several factors, including EF, associated comorbidities, and causes of death.<sup><xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B13">13</xref></sup> The present study demonstrated that the classification based on EF did not exhibit significantly different patterns of overall or in-hospital mortality rates in a sample with diverse profiles. However, the main causes of death varied between EF groups, suggesting that there is clinical and pathophysiological heterogeneity among patients with HF. Despite being more frequent, circulatory causes accounted for only approximately one-third of deaths in patients with HFrEF. Chronic respiratory diseases were the most common causes of HFmrEF. Finally, septicemia was the most prevalent specific cause of both in-hospital and late mortality, with a higher frequency in patients with lower EF. Thus, the study highlighted the importance of analyzing multiple causes of death, a rare approach in the literature, as it can reveal relevant aspects of the clinical evolution and prognosis in patients with HF.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
        <p>Focusing solely on the underlying cause of death may substantially underestimate the mortality associated with chronic diseases such as HF. The assessment of multiple causes of death used in this study provides a more comprehensive approach to analyzing mortality, enabling the examination of the association between the determinants of death from a specific disease.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Thus, the study contributes to the knowledge of the epidemiology of causes of death in patients with HF and to the development of prospective studies that enable preventive and therapeutic strategies appropriate for each EF profile. In another recent review, cardiovascular death&#8212;particularly sudden death and death associated with HF&#8212;accounted for more than half of the deaths in patients with HFpEF and an even higher proportion in those with EF below the normal range. Non-cardiovascular death remains an important contributor to death.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
        <p>Notably, HFpEF is often accompanied by chronic non-cardiac comorbidities, which contribute to the pathophysiology and prognosis of the syndrome.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> Another fact that should be highlighted in this study is the association of HFpEF with neoplasms in the correspondence analysis. One factor that may have contributed to the finding is the high average age of this sample. Older age has also been recognized as more frequent in HFpEF compared with HFrEF, which has been repeatedly confirmed in epidemiological studies of HFpEF.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> Recent data suggest that individuals who develop HFpEF are, on average, 6 years older than those who develop HFrEF,<sup><xref ref-type="bibr" rid="B17">17</xref></sup> and HFpEF accounts for a greater proportion of incident HF cases in older individuals.</p>
        <p>Approximately 10&#8211;25% of patients with HF have HFmrEF. According to the most recent evidence, these patients have an intermediate prognosis between HFrEF and HFpEF. Of note, HFmrEF is often associated with chronic non-cardiac diseases, such as hypertension, diabetes mellitus, chronic kidney disease, and anemia, which can affect the outcome of patients with HF.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Furthermore, HFmrEF is strongly associated with chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), which were more prevalent in the HFmrEF group in this sample, with a statistically significant difference. The correspondence analysis also showed a relationship between HFmrEF and endocrine and metabolic diseases, such as diabetes mellitus.</p>
        <p>Patients with HFrEF have a high risk of death from cardiovascular causes, such as acute myocardial infarction, cardiac arrhythmias, and cardiogenic shock.<sup><xref ref-type="bibr" rid="B13">13</xref>,<xref ref-type="bibr" rid="B18">18</xref></sup> In this sample, cardiovascular causes accounted for approximately 36% of the causes listed in the DCs and were more frequent in patients with HFrEF, with approximately 20% of the entries. However, other non-cardiovascular causes were also relevant, including respiratory diseases (J; 13.5% of the total), infections (A and B; 11.8%), and neoplasms (C and D; 4%), totaling around 30% of the listed causes. This finding differs from others in the national literature, in which approximately 50% of the deaths in patients with HF are attributed to the circulatory system (I) and 25% to the respiratory system (J),<sup><xref ref-type="bibr" rid="B9">9</xref></sup> probably explaining the increased mortality observed in this sample. Patients with HFpEF and HFmrEF also had an important proportion of cardiovascular causes, accounting for 7.9% and 8.3%, respectively. However, these groups also presented an important proportion of other non-cardiovascular causes, such as infections (A and B; 2.4% and 3.4%, respectively) and neoplasms (C and D; 1.0% each). Patients with HFrEF had a predominance of causes related to the circulatory system, corresponding to 19.8%. These findings are in line with the current literature, which points to septicemia as an independent risk factor for mortality in patients with HF, especially in those with systolic dysfunction.<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
        <p>The high frequency of infectious causes in groups with specific conditions related to hospital admission and late deaths is also important in this context, as it was the most common cause of death in this sample. A French multicenter study of 581 patients admitted to intensive care units with acute HF revealed a 20% infection rate among them.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> The age range of 60 years, which is close to the minimum age of the present sample, along with the infectious process, increased the morbidity and mortality of these patients compared to younger individuals.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup> In another multicenter French study with 4,252 adult patients, 429 developed in-hospital infections. The presence of comorbidities, neoplasia, neutropenia, previous use of antimicrobial agents, admission to an intensive care unit, transfer from another hospital, tracheal intubation for more than 24 hours, and prolonged stay were independently associated with hospital infection.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> Older individuals often require hospitalization to manage their medical conditions; however, infections acquired in a hospital environment are especially important in this group due to their high mortality rate.<sup><xref ref-type="bibr" rid="B21">21</xref></sup></p>
        <p>In this context, the advanced age of the current sample also influenced the patterns of deaths related to the circulatory system. In the groups organized by specific conditions, it is worth noting that HF (I50), which had the highest proportion in a Brazilian study, with a frequency of 23.26%,<sup><xref ref-type="bibr" rid="B5">5</xref></sup> was not the most common entry in the DCs in this sample. At the hospital level, the highest proportion of HF (I50) was observed in the HFmrEF group compared with the HFpEF group. There was also a gradient among entries of HF (I50), infectious causes, and acute and chronic ischemic diseases, with a change in frequency related to HFrEF, HFmrEF, and HFpEF, respectively. The presence of these causes of death also confirms that the risk of death after hospitalization due to HF remains high 12&#8211;18 months after the event.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> Rates of HF readmission in young adults are similar to those in older individuals, suggesting that the risk of rehospitalization is present regardless of age.<sup><xref ref-type="bibr" rid="B24">24</xref></sup></p>
        <p>Advanced age has also been recognized as more frequent in HFpEF compared with HFrEF and has been repeatedly confirmed in epidemiological studies of HFpEF.<sup><xref ref-type="bibr" rid="B16">16</xref></sup></p>
        <p>Since the 20th century, there has been a notable increase in longevity worldwide, primarily due to improved control of communicable diseases and advancements in sanitary measures, which have led to a higher prevalence of chronic diseases. However, this increase in longevity is reduced by population aging and growth, resulting in real rises in mortality from age-related cardiovascular diseases, increased tobacco use, and an atherogenic diet. However, there has been a decrease in deaths caused by cardiovascular diseases worldwide in recent years, thanks to the development of targeted treatments, which further increases life expectancy.<sup><xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup> Notably, HF is a common condition with rising incidence, driven in part by an aging population. Epidemiological data confirm this trend and identify age over 65 years as a risk factor for developing HF.<sup><xref ref-type="bibr" rid="B27">27</xref>-<xref ref-type="bibr" rid="B33">33</xref></sup></p>
        <p>A previous study analyzing the same sample found no significant difference in mortality among the EF groups during a follow-up of 2.94 &#177; 2.55 years. The survival curve showed no difference between HFpEF and HFmrEF, nor between HFpEF and HFrEF, although a difference was observed between patients with HF with intermediate EF and HFrEF (<xref ref-type="fig" rid="f10">Figure 4</xref>). The study's hypothesis that EF categorization could be a predictive variable for in-hospital and late death was not supported by an analysis using machine learning. The multiple causes of death in this population were not analyzed in the study and were included in another study.<sup><xref ref-type="bibr" rid="B33">33</xref></sup></p>
        <p>The main limitations of the present study relate to the challenge of completing DCs, which affects the quality of information on causes of death. Another relevant limitation is that data from 21 DCs in the sample were missing, preventing a complete interpretation. However, data were obtained from 266 DCs (93%), totaling 977 entries, and there was no impact on their clinical interpretation.</p>
        <p>This study contributes to a broader understanding of the various factors associated with HF, in particular its relationship with EF and age-related chronic diseases. To date, no studies have linked mortality from multiple causes to EF. This analysis has improved insight into the mechanisms behind HF and chronic diseases and may lead to hypotheses for developing treatment strategies to prevent morbidity and mortality.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>This study highlights the importance of analyzing multiple causes of death, which can uncover important aspects of the clinical course and prognosis of patients with HF that are not captured when only the underlying causes of death are analyzed. In this sample, a high occurrence of multiple causes of in-hospital and late deaths unrelated to the circulatory system was observed in patients admitted for decompensated HF, regardless of whether they had reduced EF (HFrEF), mildly reduced EF (HFmrEF), or preserved EF (HFpEF). These causes seem to be primarily linked to advanced age and chronic comorbidities rather than the HF syndrome itself. Prospective studies are necessary to confirm these findings and to determine the most suitable strategies for each HF phenotype.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure" id="fn5">
          <label>Sources of funding</label>
          <p>There were no external funding sources for this study.</p>
        </fn>
        <fn fn-type="other" id="fn6">
          <label>Study association</label>
          <p>This article is part of the thesis of master submitted by Giovanni Possamai Dutra, from Universidade Federal do Rio de Janeiro.</p>
        </fn>
        <fn fn-type="other" id="fn7">
          <label>Ethics approval and consent to participate</label>
          <p>This study was approved by the Ethics Committee of the Instituto D&#180;Or de Ensino e Pesquisa under the protocol number 3582453. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013.</p>
        </fn>
        <fn fn-type="other" id="fn8">
          <label>Use of Artificial Intelligence</label>
          <p>The authors did not use any artificial intelligence tools in the development of this work.</p>
        </fn>
      </fn-group>
      <sec sec-type="data-availability" specific-use="data-in-article">
        <label>Data Availability</label>
        <p>The underlying content of the research text is contained within the manuscript.</p>
      </sec>
      <app-group>
        <app id="app2">
          <label>*Supplemental Materials</label>
          <p>For additional information, please <ext-link ext-link-type="uri" xlink:href="http://abccardiol.org/supplementary-material/2025/12209/2024-0475_AO_material-suplementar_ing.pdf">click here</ext-link>.</p>
        </app>
      </app-group>
    </back>
  </sub-article>
</article>
