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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">abcimg</journal-id>
<journal-title-group>
<journal-title>ABC Imagem Cardiovascular</journal-title>
<abbrev-journal-title abbrev-type="publisher">Arq Bras Cardiol: Imagem cardiovasc.</abbrev-journal-title></journal-title-group>
<issn pub-type="epub">2675-312X</issn>
<publisher>
<publisher-name>Sociedade Brasileira de Cardiologia</publisher-name></publisher>
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<article-meta>
<article-id pub-id-type="doi">10.36660/abcimg.20240114i</article-id>
<article-id pub-id-type="publisher-id">abcimg.20240114i</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Editorial</subject>
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<title-group>
<article-title>Quantification of Myocardial Fibrosis by Cardiac Magnetic Resonance Imaging: Advances, Impacts, and Perspectives</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0003-1418-9361</contrib-id>
<name><surname>Costa</surname><given-names>Isabela Bispo Santos da Silva</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c1"/>
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<aff id="aff1">
<label>1</label>
<institution content-type="orgname">Universidade de São Paulo</institution>
<institution content-type="orgdiv1">Instituto do Câncer do Estado de São Paulo</institution>
<addr-line>
<named-content content-type="city">São Paulo</named-content>
<named-content content-type="state">SP</named-content>
</addr-line>
<country country="BR">Brazil</country>
<institution content-type="original">Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP - Brazil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c1"><label>Mailling Address:</label> <bold>Isabela Bispo Santos da Silva Costa</bold> • Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo. Av. Dr. Arnaldo, 251. Postal code: <postal-code>01246-000</postal-code>. São Paulo, SP - Brazil E-mail: <email>isabelabispo@yahoo.com.br</email></corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub">
<day>13</day>
<month>12</month>
<year>2024</year></pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2024</year>
</pub-date>
<volume>37</volume>
<issue>4</issue>
<elocation-id>e20240114</elocation-id>
<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>
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<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>Endomyocardial Fibrosis</kwd>
<kwd>Magnetic Resonance Imaging</kwd>
<kwd>Cardiomyopathies</kwd>
</kwd-group>
<counts>
<fig-count count="0"/>
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<ref-count count="11"/>
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</front>
<body>
<p>Cardiac magnetic resonance imaging (CMR) has been established as a fundamental tool for the diagnosis and management of cardiomyopathies, especially due to its accuracy in tissue characterization, identification, and quantification of myocardial fibrosis.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup> Late gadolinium enhancement (LGE) allows accurate assessment, identifying areas of myocardial fibrosis, and it serves to characterize, locate, and quantify them.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> In recent years, the role of LGE in the risk stratification of patients with hypertrophic cardiomyopathy (HCM) and other genetic cardiomyopathies has been the subject of several studies that aimed to correlate the presence and extent of myocardial fibrosis with the risk of sudden cardiac death (SCD) and major cardiovascular events.<sup><xref ref-type="bibr" rid="B4">4</xref>-<xref ref-type="bibr" rid="B6">6</xref></sup></p>
<p>Different techniques are currently used to acquire, analyze, and quantify LGE by CMR. The presence of LGE is based on the differential tissue retention of gadolinium, which is preferentially absorbed in areas of fibrosis, where scar tissue is altered due to the presence of collagen.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> LGE acquisition techniques nowadays are fast, safe, and can be performed without requiring long respiratory pauses, as was the case in the past, with progressively better resolution and image definition. To quantify areas of fibrosis, different software programs that allow adequate quantification in a semi-automated manner are currently available.</p>
<p>Kiaos et al., in a recent meta-analysis with 11 studies evaluating the quantification of myocardial fibrosis and risk of sudden death in patients with HCM offered a robust and comprehensive view of this correlation, leading to new reflections and perspectives in clinical practice.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> In this study, they analyzed almost 5,550 patients with a mean follow-up of 5.2 years and mean patient age of 51 years. The rate of sudden death events was 4.4%, and LGE was present in 61% of patients. The published data showed a statistically significant association between the presence of LGE and an increased risk of adverse events, including SCD. The odds ratio of the association between the extent of LGE and SCD was 4.93 (95% confidence interval: 3.75 to 6.47), reinforcing that the extent of fibrosis measured by LGE has been shown to be a strong predictor of SCD in these patients.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
<p>In this meta-analysis, fibrosis was quantified in 4 different manners. In 7 studies, LGE was measured using the technique &gt; 6 standard deviations (SD) from normal myocardium and quantified as a percentage of left ventricular mass. Two studies quantified LGE manually. One study quantified LGE with the 4 SD technique, and one study used the 2 SD technique. It is important to highlight that, despite the different methodologies used, the study authors assessed that there was no statistically significant difference in the prediction of SCD between these 4 methods used (p = 0.443).<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
<p>Classic studies on quantification of LGE on CMR to predict the risk of SCD in HCM used the 2 SD technique, and, based on this, the 15% cutoff point was validated in the literature<sup><xref ref-type="bibr" rid="B8">8</xref></sup> and indicated in the leading guidelines on the topic as a prognostic marker.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup> The European guidelines on cardiomyopathies published in 2023 maintain the recommendation to first estimate the risk of SCD using SCD-HCM risk calculators. For patients in the low to intermediate risk category, the presence of extensive LGE (≥ 15%) can be used in shared decision-making with patients about prophylactic implantation of an implantable cardioverter-defibrillator.</p>
<p>Magalhaes et al.,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> in the Brazilian cardiology guidelines published this year, reinforced that the presence of myocardial fibrosis greater than 15% of the left ventricular mass is a prognostic predictor in HCM and that LGE can be quantified using dedicated software or estimated visually. In addition to quantifying myocardial fibrosis, the guideline reaffirms other prognostic factors visualized by CMR that can assist clinicians in risk stratification of patients with HCM, namely: left ventricular ejection fraction less than 50%, left ventricular wall thickness greater than 30 mm, and presence of apical aneurysm. Other poor prognostic factors mentioned included left atrial enlargement and the presence of outflow tract obstruction. The Brazilian guideline lists CMR as class of recommendation I, level of evidence A in patients with suspected HCM for investigation of myocardial fibrosis for risk stratification and differential diagnosis with other heart diseases with hypertrophic phenotypes.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
<p>These data provide us with clinical implications that patients with HCM and extensive fibrosis identified by LGE may benefit from closer monitoring and, in some cases, from the indication for an implantable cardioverter-defibrillator, which may be essential for the prevention of sudden death in high-risk patients. Moreover, quantification of fibrosis may assist in longitudinal follow-up, allowing the assessment of disease progression and the efficacy of interventions, aiding in the definition of septal reduction therapy.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup> However, in initial studies with the cardiac myosin inhibitors (mavacamten and aficamten) used in HCM, they seem not to have any benefits in relation to reducing myocardial fibrosis.<sup><xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B11">11</xref></sup></p>
<p>Accordingly, it is clear that quantification and characterization of myocardial fibrosis play an important role in these patients. With technological advances, the incorporation of new methodologies, the integration of artificial intelligence, and advanced image analysis, there are future prospects that these data will become increasingly accurate, and analyses will be faster every day. Artificial intelligence has the potential to optimize fibrosis quantification and reduce interobserver variability, allowing more patients to benefit from personalized risk analysis. Furthermore, the development of contrast-enhanced CMR techniques with higher resolution may further improve the accuracy of LGE, especially in cases with less extensive fibrosis.</p>
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</article-categories>
<title-group>
<article-title>Quantificação da Fibrose Miocárdica pela Ressonância Magnética Cardíaca: Avanços, Impactos e Perspectivas</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0003-1418-9361</contrib-id>
<name><surname>Costa</surname><given-names>Isabela Bispo Santos da Silva</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c2"/>
</contrib>
<aff id="aff2">
<label>1</label>
<addr-line>
<named-content content-type="city">São Paulo</named-content>
<named-content content-type="state">SP</named-content>
</addr-line>
<country country="BR">Brasil</country>
<institution content-type="original">Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP - Brasil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c2"><label>Correspondência:</label> <bold>Isabela Bispo Santos da Silva Costa</bold> • Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo. Av. Dr. Arnaldo, 251. CEP: <postal-code>01246-000</postal-code>. São Paulo, SP - Brasil E-mail: <email>isabelabispo@yahoo.com.br</email></corresp>
</author-notes>
<kwd-group xml:lang="pt">
<title>Palavras-chave</title>
<kwd>Fibrose Endomiocárdica</kwd>
<kwd>Imageamento por Ressonância Magnética</kwd>
<kwd>Cardiopatias</kwd>
</kwd-group>
</front-stub>
<body>
<p>A ressonância magnética cardíaca (RMC) tem se consolidado como uma ferramenta fundamental para o diagnóstico e manejo das cardiomiopatias, especialmente pela sua precisão na caracterização tecidual, identificação e quantificação da fibrose miocárdica.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup> A técnica de realce tardio (RT) miocárdico (LGE, do inglês <italic>late gadolinium enhancement</italic>) permite uma avaliação precisa, identificando áreas de fibrose miocárdica e serve para caracterizar, localizar e quantificar.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Nos últimos anos, o papel do RT na estratificação de risco de pacientes com cardiomiopatia hipertrófica (CMH) e de outras cardiomiopatias genéticas tem sido objeto de diversos estudos, que buscam correlacionar a presença e a extensão da fibrose miocárdica com o risco de morte súbita cardíaca (MSC) e eventos cardiovasculares maiores.<sup><xref ref-type="bibr" rid="B4">4</xref>-<xref ref-type="bibr" rid="B6">6</xref></sup></p>
<p>Diferentes técnicas hoje são utilizadas para adquirir, analisar e quantificar o RT por RMC. A presença de RT é baseada na retenção diferencial do gadolínio nos tecidos, sendo absorvido preferencialmente em áreas de fibrose, onde o tecido cicatricial é alterado devido à presença de colágeno.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> As técnicas de aquisição do RT hoje são rápidas, seguras e podem ser feitas sem a necessidade de longas pausas respiratórias, como feitas no passado, com resolução e definição de imagens progressivamente melhores. Para quantificação das áreas de fibrose, hoje são disponíveis diferentes softwares que permitem de forma semiautomatizada a quantificação adequada.</p>
<p>Kiaos et al. em uma metanálise recente com 11 estudos avaliando a quantificação de fibrose miocárdica e risco de morte súbita em pacientes com CMH trouxe à tona uma visão robusta e abrangente dessa correlação, impulsionando novas reflexões e perspectivas na prática clínica.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Nesse estudo, eles analisaram quase 5.550 pacientes com média de seguimento de 5,2 anos e idade média dos pacientes de 51 anos. A taxa de eventos de morte súbita foi de 4,4% e RT estava presente em 61% dos pacientes. Os dados publicados mostram uma associação estatisticamente significativa entre a presença de RT e um risco aumentado de eventos adversos, incluindo MSC. A <italic>odds ratio</italic> da associação entre a extensão de RT e MSC foi de 4,93 (intervalo de confiança de 95%: 3,75 a 6,47), reforçando que a extensão da fibrose medida pela RT tem se mostrado um forte preditor de MSC nesses pacientes.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
<p>Nessa metanálise, a quantificação da fibrose foi feita de 4 formas diferentes. Em 7 estudos, o RT foi mensurado pela técnica &gt; 6 desvios padrões (DP) do miocárdio normal e quantificado como porcentagem da massa do ventrículo esquerdo. Dois estudos quantificaram o RT manualmente, um estudo quantificou o RT com a técnica de 4 DP, e um estudo com a técnica de 2 DP. É importante ressaltar que apesar das diferentes metodologias utilizadas, autores avaliaram no estudo que não houve diferença estatisticamente significativa na predição de MSC entre esses 4 métodos utilizados (p = 0,443).<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
<p>Os trabalhos clássicos de quantificação de RT pela RMC na predição de risco de MSC na CMH utilizaram a técnica de 2 DP e a partir daí o ponto de corte de 15% foi validado na literatura<sup><xref ref-type="bibr" rid="B8">8</xref></sup> e indicado nas principais diretrizes sobre o tema como marcador prognóstico.<sup><xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B2">2</xref></sup> As diretrizes europeias de cardiomiopatias publicadas em 2023 mantém a recomendação de primeiro estimar o risco de MSC usando as calculadoras de risco de MSC-CMH. Para pacientes que estão na categoria de risco baixo a intermediário, a presença de RT extenso (≥ 15%) pode ser utilizada na tomada de decisão compartilhada com os pacientes sobre o implante profilático de cardiodesfibrilador implantável.</p>
<p>Magalhaes et al.,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> nas diretrizes brasileiras de cardiologia publicadas este ano, reforçam a presença de fibrose miocárdica maior que 15% da massa do ventrículo esquerdo como preditor prognóstico na CMH e que a quantificação do RT pode ser feita por software dedicado ou estimada visualmente. Além da quantificação de fibrose miocárdica, esta diretriz reafirma outros fatores prognósticos visualizados pela RMC que podem auxiliar o clínico na estratificação de risco de pacientes com CMH, a saber: fração de ejeção do ventrículo esquerdo menor que 50%; espessura ventricular esquerda maior que 30 mm; e presença de aneurisma apical. Outros fatores de mau prognóstico citados são aumento de átrio esquerdo e a presença de obstrução da via de saída. A diretriz brasileira traz a RMC como classe de recomendação I, nível de evidência A para pacientes com suspeita de CMH, para pesquisa de fibrose miocárdica para estratificação de risco e diagnóstico diferencial com outras cardiopatias de fenótipos hipertróficos.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
<p>Esses dados nos trazem como implicações clínicas que pacientes com CMH e extensa fibrose identificada pelo RT podem se beneficiar de uma monitorização mais próxima e, em alguns casos, da indicação de um cardiodesfibrilador implantável, que pode ser essencial para a prevenção de morte súbita em indivíduos de alto risco. Além disso, a quantificação da fibrose pode auxiliar no acompanhamento longitudinal, permitindo avaliar a progressão da doença e a eficácia das intervenções, auxiliando na definição sobre terapia de redução septal.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup> Entretanto, nos estudos iniciais com os inibidores da miosina cardíaca (mavacanteno e aficanteno) utilizados na CMH, eles parecem não ter benefício na redução da fibrose miocárdica.<sup><xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B11">11</xref></sup></p>
<p>Dessa forma, fica claro o papel importante da quantificação e caracterização da fibrose miocárdica nesses pacientes. As perspectivas futuras com o avanço tecnológico e incorporação de novas metodologias, a integração da inteligência artificial (IA) e a análise de imagem avançada são de que cada dia esses dados sejam mais precisos e as análises mais rápidas. A IA tem o potencial de otimizar a quantificação da fibrose e reduzir a variabilidade interobservador, permitindo que mais pacientes se beneficiem de uma análise de risco personalizada. Além disso, o desenvolvimento de técnicas de RMC com aprimoramento do contraste e maior resolução pode melhorar ainda mais a acurácia do RT, especialmente em casos com menor extensão de fibrose.</p>
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