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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">abcic</journal-id>
<journal-title-group>
<journal-title>ABC Imagem Cardiovascular</journal-title>
<abbrev-journal-title abbrev-type="publisher">ABC Imagem Cardiovasc.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">2675-312X</issn>
<issn pub-type="ppub">2318-8219</issn>
<publisher>
<publisher-name>Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiolodia (DIC/SBC)</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.36660/abcimg.20260016i</article-id>
<article-id pub-id-type="other">abcimg.20260016i</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>The Use of Artificial Intelligence in the Diagnosis of Cardiac Amyloidosis: Integrative Review</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-2331-6871</contrib-id>
<name><surname>Lemos</surname><given-names>Nilson Batista</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="c1"/>
<role>Conception and design of the research</role>
<role>analysis and interpretation of the data</role>
<role>writing of the manuscript and critical revision of the manuscript for intellectual content</role>
<role>obtaining financing</role>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0009-0006-1640-0975</contrib-id>
<name><surname>Araújo</surname><given-names>Gabriela Aparecida Moreira</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<role>Conception and design of the research</role>
<role>analysis and interpretation of the data</role>
<role>writing of the manuscript and critical revision of the manuscript for intellectual content</role>
<role>obtaining financing</role>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0001-8809-8783</contrib-id>
<name><surname>Melo</surname><given-names>Marcelo Dantas Tavares de</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<role>Conception and design of the research</role>
<role>analysis and interpretation of the data</role>
<role>writing of the manuscript and critical revision of the manuscript for intellectual content</role>
</contrib>
<aff id="aff1">
<label>1</label>
<institution content-type="orgname">Universidade Federal da Paraíba</institution>
<addr-line>
<named-content content-type="city">João Pessoa</named-content>
<named-content content-type="state">PB</named-content>
</addr-line>
<country country="BR">Brazil</country>
<institution content-type="original">Universidade Federal da Paraíba, João Pessoa, PB – Brazil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c1"><label>Correspondência:</label> <bold>Nilson Batista Lemos</bold> • Universidade Federal da Paraíba. Campus I Lot., Cidade Universitaria. CEP: <postal-code>58051-900</postal-code>. João Pessoa, PB – Brasil E-mail: <email>nilsonlemos18@gmail.com</email></corresp>
<fn fn-type="coi-statement"><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 responsável pela revisão:</label><p>Marcelo Tavares</p></fn>
</author-notes>
<pub-date publication-format="electronic" date-type="pub">
<day>01</day>
<month>04</month>
<year>2026</year></pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2026</year></pub-date>
<volume>39</volume>
<issue>1</issue>
<elocation-id>e20260016</elocation-id>
<history>
<date date-type="received">
<day>08</day>
<month>02</month>
<year>2026</year>
</date>
<date date-type="rev-recd">
<day>09</day>
<month>02</month>
<year>2026</year>
</date>
<date date-type="accepted">
<day>09</day>
<month>02</month>
<year>2026</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>Abstract</title>
<sec>
<title>Fundamento:</title>
<p>Cardiac amyloidosis is a rare form of infiltrative cardiomyopathy characterized by the deposition of proteins in the myocardium, resulting in increased wall thickness, impaired ventricular function, and possible progression to heart failure. Diagnosis is challenging due to the low prevalence of the disease and the nonspecific nature of its clinical manifestations. The application of artificial intelligence (AI) to the analysis of medical tests emerges as a promising strategy for early detection, more accurate diagnosis, and timely initiation of treatment.</p>
</sec>
<sec>
<title>Methods:</title>
<p>An integrative literature review was conducted on the use of AI in the diagnosis of cardiac amyloidosis. Articles published between 2019 and 2024 were searched in the PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases.</p>
</sec>
<sec>
<title>Results:</title>
<p>Of the 420 articles initially identified, 21 met the eligibility criteria and were included in the final analysis. A predominance of retrospective observational studies applying machine learning models was observed. Among the diagnostic modalities evaluated in association with AI, electrocardiography and echocardiography were the most frequently studied tests.</p>
</sec>
<sec>
<title>Conclusion:</title>
<p>AI demonstrates high potential to improve the screening and diagnosis of cardiac amyloidosis when applied to the analysis of clinical and imaging tests. The findings of this review indicate that AI may accelerate the diagnostic process, reduce the need for invasive procedures, and optimize the use of health care resources. However, to expand its integration into clinical practice and enhance its generalizability, further model refinement and validation in more diverse populations are required.</p>
</sec>
</abstract>
<kwd-group xml:lang="en">
<title>Keywords:</title>
<kwd>Amyloidosis</kwd>
<kwd>Artificial Intelligence</kwd>
<kwd>Diagnosis</kwd>
</kwd-group>
<funding-group>
<funding-statement><bold>Sources of Funding</bold>: There were no external funding sources for this study.</funding-statement>
</funding-group>
<counts>
<fig-count count="4"/>
<table-count count="2"/>
<equation-count count="0"/>
<ref-count count="21"/>
</counts>
</article-meta>
</front>
<body>
<sec sec-type="intro">
<title>Introduction</title>
<p>Amyloidosis is a generic term used to describe the extracellular deposition of fibrils formed by low-molecular-weight protein subunits derived from different precursor proteins. Amyloid deposits may result in a wide variety of clinical manifestations, which vary according to the type of protein involved, the amount deposited, and the tissue location. In the genesis of these deposits, initially soluble peptides undergo conformational changes, predominantly acquiring an antiparallel beta-pleated sheet structure, which favors their stacking into twisted fibrils.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
<p>There are dozens of systemic and localized forms of amyloidosis. Among them, four precursor proteins may give rise to both localized and systemic deposits. The main systemic forms are immunoglobulin light-chain (AL) amyloidosis and (ATTR) transthyretin amyloidosis. These forms are named according to the precursor protein of the amyloid deposit (AL or ATTR) and account for approximately 95% of cases of cardiac amyloidosis. The remaining forms correspond to other subtypes of amyloidosis, which are also clinically relevant.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
<p>ATTR amyloidosis is characterized by the misfolding and subsequent deposition of transthyretin, a protein responsible for the transport of thyroid hormone and vitamin A. It may present in wild-type or hereditary form.<sup><xref ref-type="bibr" rid="B2">2</xref>-<xref ref-type="bibr" rid="B4">4</xref></sup> Similarly, AL amyloidosis results from the accumulation of misfolded immunoglobulin light chains produced by plasma cells associated with dyscrasias.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
<p>In cardiac amyloidosis, it is a rare form of progressive cardiomyopathy whose population prevalence has not yet been well established.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> The disease is caused by myocardial deposition of misfolded amyloid proteins, resulting in restrictive cardiomyopathy, with possible progression to heart failure, conduction system disorders, and cardiac death.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> It may present with cardiovascular signs and symptoms or be diagnosed during the investigation of extracardiac manifestations of the disease.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> Due to its heterogeneous clinical phenotype and frequently nonspecific manifestations, diagnosis and management tend to occur late.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
<fig id="f1">
<graphic xlink:href="2675-312X-abcic-39-1-e20260016-gf01.tif"/>
</fig>
<p>With regard to the diagnostic approach to cardiac amyloidosis, it is essential to recognize clinical scenarios and abnormalities in complementary tests that indicate the need for investigation. However, diagnosis is challenging, especially because it is often an indolent disease whose symptoms may overlap with those of more prevalent heart diseases.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> Depending on the clinical context and resource availability, various tools may be employed, including electrocardiography (ECG), echocardiography, cardiac magnetic resonance (CMR), bone-seeking tracers scintigraphy, monoclonal protein screening by immunofixation, and biopsy of the affected tissue. Each method has its own characteristics and different levels of diagnostic accuracy (Central Illustration).</p>
<p>Some findings may increase clinical suspicion of cardiac amyloidosis, such as discordance between increased left ventricular (LV) wall thickness and low QRS voltage, unexplained LV hypertrophy, low-flow, low-gradient aortic stenosis, relative apical sparing of longitudinal strain, a diffuse circumferential subendocardial late gadolinium enhancement pattern of the LV on CMR, and myocardial uptake of bone tracers on bone-seeking tracers scintigraphy.</p>
<p>Despite the diversity of available diagnostic methods, cardiac amyloidosis remains underdiagnosed,<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B5">5</xref>-<xref ref-type="bibr" rid="B7">7</xref></sup> which has important repercussions for patients’ quality of life. At the same time, the development of therapies capable of improving clinical outcomes has driven the search for strategies to increase diagnostic rates. These interventions may reduce or stabilize protein deposition, with a consequent reduction in the relative risk of hospitalizations, morbidity, and mortality associated with the disease.</p>
<p>Because of the need for early detection of cardiac amyloidosis, the development of mechanisms that optimize screening and diagnosis with lower costs and risks is essential.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> This review aims to present the main advances in disease detection, with emphasis on promising technological tools in diagnostic medicine, especially artificial intelligence (AI).</p>
<p>AI is a branch of computer science dedicated to the development of systems capable of performing tasks that simulate human cognitive functions, such as decision-making and complex reasoning. In the field of medical diagnosis, these systems are trained using machine learning techniques, in which large volumes of data, often images, are used for pattern recognition. Among the most commonly employed approaches are convolutional neural networks (CNNs), which consist of multiple layers that extract progressively more complex features from the analyzed data, enabling automated identification of patterns in images and other types of information. In general, the larger and more representative the dataset used for training, the greater the model&apos;s accuracy tends to be.</p>
<p>Incorporating AI into medical practice enables the more effective screening of rare diseases and improves diagnostic accuracy. AI appears particularly promising for rare diseases that are often underrecognized in clinical practice. Automated systems can integrate multiple signs, symptoms, and complementary findings, helping to guide clinical reasoning. Thus, core skills in medicine, such as pattern recognition, are increasingly being incorporated into computational models with the aim of enhancing diagnostic reliability and supporting decision-making in everyday medical practice.</p>
<p>Several studies have investigated the applicability of AI in the early diagnosis of cardiac amyloidosis. Among the most recent approaches are the integration of AI with imaging methods, such as positron emission tomography (PET-CT), bone-seeking tracers scintigraphy, and CMR as well as its application to the automated analysis of ECGs, genetic data, and phenotypic profiles of cardiac abnormalities. These aspects will be discussed throughout this review.</p>
</sec>
<sec sec-type="methods">
<title>Methods</title>
<p>The present study is characterized as an integrative literature review aimed at critically analyzing the use of AI in the diagnosis of cardiac amyloidosis. The review was conducted following six methodological steps: i) definition of the research question; ii) establishment of inclusion criteria and sample selection; iii) identification of preselected and selected studies; iv) organization and representation of the included studies; v) critical analysis of the data; and vi) synthesis of the available knowledge.</p>
<p>Searches were conducted in the PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases. The search strategy was developed using the descriptors &quot;artificial intelligence,&quot; &quot;amyloidosis,&quot; and &quot;diagnosis,&quot; included in the Medical Subject Headings and Embase Subject Headings, combined using the Boolean operator AND.</p>
<p>Original studies and meta-analyses published between 2019 and 2024 that evaluated the application of AI in the diagnosis of cardiac amyloidosis were included. Articles that did not meet the inclusion criteria were excluded, as well as narrative reviews, case reports, editorials, and studies with methodology considered inadequate.</p>
<p>After article selection, methodological quality was assessed to ensure greater rigor in the interpretation of findings and robustness of the conclusions. For this step, the JBI critical appraisal tool was used, which includes specific criteria according to study design, covering aspects related to the sample, methodology, data analysis, bias control, and ethical considerations. Quality classification is based on the proportion of affirmative responses to the evaluated criteria, allowing comparison across studies and critical analysis of their results.</p>
</sec>
<sec sec-type="results">
<title>Results</title>
<p>The search strategy yielded 420 articles, distributed as follows: 124 identified in PubMed, 61 in Web of Science, 84 in Scopus, 147 in Embase, and 4 in the Cochrane Library. After removal of 192 duplicate studies, 228 articles remained for screening.</p>
<p>Title and abstract screening resulted in the selection of 43 studies for full-text evaluation. After application of the eligibility criteria, 21 articles were included in the final analysis (<xref ref-type="fig" rid="f2">Figure 1</xref>).</p>
<fig id="f2">
<label>Figure 1</label>
<caption><title>Flowchart of the study selection process for the studies included in the integrative review.</title></caption>
<graphic xlink:href="2675-312X-abcic-39-1-e20260016-gf02.tif"/>
</fig>
<p>Regarding methodological assessment according to the JBI criteria, most studies were classified as having good to excellent methodological quality, with scores ranging from 6 to 8 points. The main factors contributing to this classification included the use of robust statistical metrics and the application of cross-validation in the developed AI models.</p>
<p>As limitations, the absence of gold-standard diagnostic confirmation of cardiac amyloidosis in part of the studies was observed, as well as the lack of external validation of the proposed models, which limits the generalizability of the findings. The detailed results of the methodological assessment are presented in <xref ref-type="table" rid="t1">Table 1</xref>.</p>
<table-wrap id="t1">
<label>Table 1</label>
<caption><title>Methodological characteristics and quality assessment of the included studies</title></caption>
<table frame="hsides" rules="groups">
<colgroup width="20%">
<col/>
<col/>
<col/>
<col/>
<col/>
</colgroup>
<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
<tr style="background-color:#C58874">
<th align="left" valign="middle">No.</th>
<th align="center" valign="middle">Study (author/year)</th>
<th align="center" valign="middle">Design</th>
<th align="center" valign="middle">Score (JBI/8)</th>
<th align="center" valign="middle">Methodological assessment</th>
</tr>
</thead>
<tbody style="border-bottom: thin solid; border-color: #000000">
<tr>
<td align="left" valign="middle">1</td>
<td align="center" valign="middle">Agibetov et al. (2021)</td>
<td align="center" valign="middle">Retrospective observational study with cardiac magnetic resonance and application of machine learning</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">High quality</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">2</td>
<td align="center" valign="middle">Barbieri et al. (2024)</td>
<td align="center" valign="middle">Study with automated three-dimensional transthoracic echocardiography associated with machine learning</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">High quality</td>
</tr>
<tr>
<td align="left" valign="middle">3</td>
<td align="center" valign="middle">Castaño et al. (2024)</td>
<td align="center" valign="middle">Retrospective case-control observational study with application of machine learning</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">High quality</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">4</td>
<td align="center" valign="middle">Cotella et al. (2023)</td>
<td align="center" valign="middle">Retrospective observational study with echocardiography and application of machine learning</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">High quality</td>
</tr>
<tr>
<td align="left" valign="middle">5</td>
<td align="center" valign="middle">Delbarre et al. (2023)</td>
<td align="center" valign="middle">Multicenter retrospective observational study with bone-seeking tracers scintigraphy analyzed by machine learning</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">Excellent</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">6</td>
<td align="center" valign="middle">Eckstein et al. (2022)</td>
<td align="center" valign="middle">Observational cohort study with echocardiography and use of machine learning</td>
<td align="center" valign="middle">6</td>
<td align="center" valign="middle">Good quality</td>
</tr>
<tr>
<td align="left" valign="middle">7</td>
<td align="center" valign="middle">Garofalo et al. (2021)</td>
<td align="center" valign="middle">Predictive computational study with experimental validation focused on genetic assessment using machine learning</td>
<td align="center" valign="middle">6</td>
<td align="center" valign="middle">Good quality</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">8</td>
<td align="center" valign="middle">Goto et al. (2021)</td>
<td align="center" valign="middle">Multicenter observational study using electrocardiography and echocardiography</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">Excellent</td>
</tr>
<tr>
<td align="left" valign="middle">9</td>
<td align="center" valign="middle">Harmon et al. (2023)</td>
<td align="center" valign="middle">Retrospective observational study with electrocardiography and application of machine learning</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">High quality</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">10</td>
<td align="center" valign="middle">Huda et al. (2021)</td>
<td align="center" valign="middle">Retrospective observational study with application of machine learning</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">High quality</td>
</tr>
<tr>
<td align="left" valign="middle">11</td>
<td align="center" valign="middle">Ma et al. (2024)</td>
<td align="center" valign="middle">Retrospective observational study with non-contrast cardiac magnetic resonance and use of machine learning</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">High quality</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">12</td>
<td align="center" valign="middle">Martini et al. (2020)</td>
<td align="center" valign="middle">Prospective observational study with cardiac magnetic resonance and application of machine learning</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">Excellent</td>
</tr>
<tr>
<td align="left" valign="middle">13</td>
<td align="center" valign="middle">Miller et al. (2024)</td>
<td align="center" valign="middle">Retrospective observational study with positron emission tomography and automated segmentation</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">Excellent</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">14</td>
<td align="center" valign="middle">Nowak et al. (2024)</td>
<td align="center" valign="middle">Retrospective observational study with cardiac magnetic resonance, T1 mapping, and use of machine learning</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">High quality</td>
</tr>
<tr>
<td align="left" valign="middle">15</td>
<td align="center" valign="middle">Santarelli et al. (2020)</td>
<td align="center" valign="middle">Prospective observational study with positron emission tomography and application of machine learning</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">High quality</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">16</td>
<td align="center" valign="middle">Schrutka et al. (2021)</td>
<td align="center" valign="middle">Prospective case-control observational study with application of machine learning</td>
<td align="center" valign="middle">6</td>
<td align="center" valign="middle">Good quality</td>
</tr>
<tr>
<td align="left" valign="middle">17</td>
<td align="center" valign="middle">Shiri et al. (2024)</td>
<td align="center" valign="middle">Prospective single-cohort observational study with application of machine learning</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">High quality</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">18</td>
<td align="center" valign="middle">Spielvogel et al. (2024)</td>
<td align="center" valign="middle">Multicenter retrospective observational study with bone-seeking tracers scintigraphy and use of machine learning</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">Excellent</td>
</tr>
<tr>
<td align="left" valign="middle">19</td>
<td align="center" valign="middle">Vrudhula et al. (2024)</td>
<td align="center" valign="middle">Retrospective observational study with application of machine learning</td>
<td align="center" valign="middle">6</td>
<td align="center" valign="middle">Good quality</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">20</td>
<td align="center" valign="middle">Yang et al. (2024)</td>
<td align="center" valign="middle">Observational study with digital histopathological analysis using a neural network and autofluorescence</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">High quality</td>
</tr>
<tr>
<td align="left" valign="middle">21</td>
<td align="center" valign="middle">Zhang et al. (2023)</td>
<td align="center" valign="middle">Retrospective observational study with echocardiography and application of machine learning</td>
<td align="center" valign="middle">6</td>
<td align="center" valign="middle">Good quality</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec sec-type="discussion">
<title>Discussion</title>
<p>The use of AI as a supportive tool in the diagnosis of rare diseases, such as cardiac amyloidosis, has been considered promising, especially in the context of conditions with high clinical heterogeneity and that are frequently underrecognized by general practitioners. Early identification of the disease may modify its natural history and improve prognosis. This review sought to emphasize the potential of already established diagnostic tools for the evaluation of cardiac amyloidosis when combined with machine learning-based systems, an approach addressed in all included studies.</p>
<p>To organize the analysis of the findings, AI performance will be discussed according to the different diagnostic modalities used in the screening and evaluation of cardiac amyloidosis.</p>
<sec>
<title>Performance of artificial intelligence in the evaluation of medical record data and laboratory tests</title>
<p>Among the screening strategies for amyloid cardiomyopathy, the use of data extracted from electronic health records of patients with heart failure (HF) with preserved ejection fraction (HFpEF) stands out. To differentiate amyloid etiology, especially wild-type ATTR amyloidosis (ATTRwt), from non-amyloid etiology, Huda et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> collected electronic health record data and developed an AI model capable of screening and identifying patients with ATTRwt amyloidosis. The system achieved an area under the receiver operating characteristic curve (AUC) of 0.80. Performance was supported by the identification of comorbidities more prevalent in the amyloid etiology group, such as atrial fibrillation and chronic kidney disease, and in the non-amyloid group, such as hypertension, diabetes mellitus, obesity, and coronary artery disease, which were used as predictive variables.</p>
<p>Subsequently, Castaño et al.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> refined the model by focusing the analysis on 11 main phenotypes associated with cardiac amyloidosis, including carpal tunnel syndrome and arrhythmias. The model demonstrated accuracy (74%), sensitivity (77%), and specificity (72%), with an AUC of 0.82. Although there was a slight reduction in some performance parameters, the model was simplified in terms of programming, facilitating its implementation in hospital settings and expanding its potential for population screening.</p>
<p>The studies by Huda et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> and Castaño et al.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> demonstrate the feasibility of automated screening through systematic extraction of clinical data, a process that would be costly and operationally complex if performed manually. Although such models are limited by the quality of records coded according to the International Classification of Diseases and by the documented phenotypes, without direct integration of laboratory or imaging tests for definitive typing, they represent relevant tools for large-scale screening, directing patients with higher probability toward further investigation.</p>
<p>Additionally, phenotypes recognized by the model, such as carpal tunnel syndrome, may precede the development of HF, which suggests a potential application of AI in preclinical stages, with implications for early identification of ATTR amyloidosis.</p>
</sec>
<sec>
<title>Performance of artificial intelligence in electrocardiographic evaluation</title>
<p>The application of AI in ECG analysis has emerged as a screening strategy, considering that ECG is a widely available, low-cost, noninvasive test.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> Model validation represents a fundamental step in the development of these tools, as it involves testing multiple variables across different populations.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
<p>Harmon et al.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> developed an algorithm applicable to diverse populations, including different races and sexes. The model achieved an AUC of 0.84 (95% CI: 0.82-0.86), maintaining consistent performance across subgroups, except in the Hispanic population, possibly underrepresented in the sample. The algorithm performed better in ECGs with low voltage and patterns compatible with prior infarction, and showed lower performance in left bundle branch block and LV hypertrophy. These findings suggest the need for greater sample diversity, without invalidating the use of the tool as a screening method.</p>
<p>Vrudhula et al.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> evaluated approximately 1.3 million ECGs from 341,989 patients. The different tested models showed AUC values ranging from 0.660 (95% CI: 0.642-0.736) to 0.898 (95% CI: 0.868-0.924), demonstrating relevant potential for screening and referral for further investigation. However, because of the rarity and underdiagnosis of cardiac amyloidosis, models are often trained with a limited number of confirmed cases.</p>
<p>Similarly, Goto et al.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> reported strong performance, with a C-statistic of 0.91 (95% CI: 0.90-0.93) in the Brigham and Women&apos;s Hospital test set, 0.85 (0.82-0.87) at Massachusetts General Hospital, and 0.86 (0.83-0.88) at the University of California, San Francisco. However, the authors emphasize that isolated ECG features do not provide sufficient sensitivity or specificity to be used as independent heuristics, and their integration with other clinical and diagnostic variables is recommended to optimize model performance.</p>
<p>Schrutka et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> also reinforce that the proposed model may assist in raising suspicion of cardiac amyloidosis even in the absence of advanced imaging methods. In that study, 20 patients with transthyretin cardiac amyloidosis, 11 with HFpEF, 30 with cardiac amyloidosis, and 50 with other HF etiologies were evaluated. The presence of a low-voltage ECG pattern associated with increased LV wall thickness was highly suggestive of cardiac amyloidosis, allowing differentiation from hypertensive or hypertrophic cardiomyopathy. In the analysis of ECG patterns, pattern 1 was present in 78% of patients with AL amyloidosis and in 58% of those with ATTR amyloidosis (p = 0.009), whereas pattern 2 was identified in 7% of AL amyloidosis cases and in 23% of ATTR amyloidosis cases (p = 0.006). The absence of a specific pattern was observed in 16% of patients with AL amyloidosis and in 18% of patients with ATTR amyloidosis (p = 0.620).</p>
</sec>
<sec>
<title>Performance of artificial intelligence in echocardiographic evaluation</title>
<p>Considering the versatility of echocardiography and its central role in the diagnostic investigation of cardiac amyloidosis, the development of AI models capable of reducing operational variability and improving diagnostic accuracy is highly relevant.</p>
<p>Xiaofeng Zhang et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> observed that there are still few studies on echocardiography-based myocardial texture analysis and that human visual assessment has limitations in characterizing these alterations. Based on transthoracic echocardiograms, the authors developed four machine learning algorithms to differentiate cardiac amyloidosis from other cardiomyopathies: random forest (RF), support vector machine (SVM), logistic regression (LR), and gradient boosting decision trees (GBDT).</p>
<p>In the analyzed population, all models were able to effectively distinguish cases of cardiac amyloidosis from non-amyloid diseases. The LR model demonstrated the best diagnostic performance, outperforming the traditional ultrasonographic method (AUC: RF 0.77; SVM 0.81; LR 0.81; GBDT 0.71). The authors therefore proposed the application of this tool as a noninvasive diagnostic method for myocardial amyloidosis. However, the relatively small number of cardiac amyloidosis cases may have limited the model&apos;s sensitivity for discrimination between groups.</p>
<p>Cotella et al.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> developed an AI model focused on the automated assessment of LV ejection fraction (LVEF) and global longitudinal strain (GLS), central parameters in the diagnosis of cardiac amyloidosis. The authors justified the incorporation of AI based on the fact that manual measurements are time-consuming and show significant inter- and intraobserver variability, which may compromise diagnostic accuracy and influence therapeutic decisions. The study demonstrated that automated and quantitative measurements of LVEF and GLS showed high accuracy and enabled sensitive and specific detection of abnormalities when compared with conventional manual analysis, both in examinations performed before the diagnosis of cardiac amyloidosis and at the time of diagnosis. No statistically significant differences were observed between values obtained by the two methods in the prediagnostic period (LVEF: p = 0.791; GLS: p = 0.105) or at the time of diagnosis (LVEF: p = 0.463; GLS: p = 0.722). In addition, a strong correlation was observed between automated and manual measurements in echocardiograms performed before diagnosis (r = 0.78 for LVEF; r = 0.83 for GLS) and at established diagnosis (r = 0.74 for LVEF; r = 0.80 for GLS).</p>
<p>Goto et al.,<sup><xref ref-type="bibr" rid="B3">3</xref></sup> although acknowledging that ECG-based models show encouraging results, emphasize that their performance may not be sufficient for diagnosing low-prevalence diseases. The echocardiographic model developed by the authors demonstrated greater predictive accuracy compared with the ECG-based model. C-statistics ranged from 0.85-0.91 for ECG and from 0.89-1.00 for echocardiography. Moreover, in subtype analysis, the model showed superior performance in identifying ATTR amyloidosis.</p>
<p>In a more specific population, Shiri et al.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> evaluated the use of machine learning for detecting ATTR amyloidosis in patients with severe aortic stenosis. Although different diagnostic modalities are useful in the initial assessment of these patients, they are not specific for ATTR amyloidosis. Frequently, definitive diagnosis of ATTR cardiomyopathy depends on histopathological confirmation or identification of a mutation in the <italic>TTR</italic> gene associated with evidence of significant myocardial uptake on bone-seeking tracers scintigraphy. Considering the high cost of genetic testing and bone-seeking tracers scintigraphy, especially in this patient group, the authors developed a noninvasive and potentially cost-effective model based on routine clinical and echocardiographic data. Performance was satisfactory when compared with clinical, laboratory, and interventional imaging variables, with an AUC of 0.79, sensitivity of 0.80, and specificity of 0.78.</p>
<p>Based on evidence that myocardial deformation analysis provides discriminatory value across multiple cardiac chambers, Eckstein et al.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> developed a supervised model capable of differentiating cardiac amyloidosis from hypertrophic cardiomyopathy and from healthy individuals. The system showed excellent performance (AUC = 0.996; accuracy = 94%; sensitivity = 100%; F1-score = 97%), indicating that automated analysis of multichamber cardiac deformation and function may serve as a clinical decision support tool, even without the need for contrast administration.</p>
<p>With the technological advancement of cardiovascular imaging methods, new approaches have been proposed for screening infiltrative cardiomyopathies. Barbieri et al.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> developed a model based on three-dimensional transthoracic echocardiography (3D-TTE) combined with AI, aiming to differentiate various phenotypes of cardiac hypertrophy, including cardiac amyloidosis. The method proposes a reformulation of ejection fraction analysis, traditionally based on CMR, through the use of 3D-TTE integrated with an AI system. Three-dimensional acquisition allowed a more detailed and accurate analysis of LV volume, enabling a more precise calculation of ejection fraction, defined as the ratio between stroke volume and end-diastolic volume, reflecting myocardial contractile capacity. This approach provides more accurate information regarding myocardial shortening and wall thickness, key aspects in recognizing infiltrative cardiomyopathies. In conventional two-dimensional echocardiography, increased wall thickness may mask reduced myocardial shortening, resulting in an apparently preserved ejection fraction. In the context of etiological investigation of HFpEF, the model proved promising, showing higher ejection fraction in patients with hypertrophic cardiomyopathy and cardiac amyloidosis, with the latter exhibiting proportionally even higher values. Diagnostic performance was consistent, with sensitivity of 87%, specificity of 100%, and AUC of 0.959, reinforcing the potential of integrating 3D-TTE and AI in the phenotypic differentiation of myocardial hypertrophy.</p>
</sec>
<sec>
<title>Artificial intelligence in positron emission tomography evaluation</title>
<p>Similarly to other imaging modalities, PET-CT has been refined with the aim of making the diagnostic process of cardiac amyloidosis less invasive and more accurate. Deep learning-based models focused on the automated recognition of imaging patterns related to amyloid deposition stand out.</p>
<p>Santarelli et al.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> developed a model aimed at rapidly, early, and specifically identifying the presence of cardiac amyloidosis and its subtypes. The system demonstrated superior performance compared with analysis performed by a specialist with more than 10 years of experience, showing sensitivity greater than 0.8 and specificity greater than 0.89. The model was able to estimate the probability of correlation between the analyzed image and each subtype of cardiac amyloidosis. The authors also highlighted the risk of overfitting, especially in scenarios with a limited number of images available for training. In such cases, the algorithm may show high performance on training data but fail to generalize to external datasets. To mitigate this risk, strategies such as artificial data augmentation and cross-validation were employed, contributing to greater model robustness.</p>
<p>In the study by Miller et al.,<sup><xref ref-type="bibr" rid="B13">13</xref></sup> it is recognized that visual interpretation of single-photon emission computed tomography constitutes the standard approach in the diagnostic evaluation of ATTR amyloidosis, although it is inherently subjective. The authors assessed a deep learning approach for automated volumetric quantification of technetium-99m (<sup>99m</sup>Tc)-pyrophosphate, using segmentation of anatomical structures co-registered on computed tomography attenuation maps in patients with suspected ATTR amyloidosis. The results demonstrated that deep learning-based segmentation was not influenced by the radiotracer uptake pattern and allowed automated quantification of focal uptake images, such as those obtained with <sup>99m</sup>Tc-pyrophosphate. The model showed excellent performance (AUC = 0.989; 95% CI: 0.974-1.00), indicating potential for accurate identification of patients with ATTR amyloidosis. Therefore, this approach shows potential for precise identification of patients with ATTR amyloidosis.</p>
</sec>
<sec>
<title>Performance of artificial intelligence in the evaluation of bone-seeking tracers scintigraphy</title>
<p>In the context of diagnosing cardiac amyloidosis through the application of AI to imaging analysis, it is possible to structure systems integrated into electronic health records, similar to the model described by Huda et al.,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> but directed toward the automated interpretation of scintigraphy images.</p>
<p>Delbarre et al.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> proposed a deep learning model for automated analysis of whole-body <sup>99m</sup>Tc bone-seeking tracers scintigraphy, based on the premise that significant cardiac uptake on these examinations is strongly suggestive of ATTR amyloidosis. The model demonstrated sensitivity of 98.9% and specificity of 99.5% in cross-validation. In external validation, a slight reduction in sensitivity to 96.1% was observed, while specificity remained at 99.5%, with an AUC of 0.999 in both stages.</p>
<p>For system development, cardiac uptake ≥ 2 according to the Perugini grading scale was used as a predictive variable. The algorithm was trained using CNNs with image-level labels extracted from examinations recorded in electronic health records, enabling automated identification of patterns suggestive of cardiac amyloidosis. As also emphasized by Castaño et al.,<sup><xref ref-type="bibr" rid="B9">9</xref></sup> integration between AI and electronic record systems supports efficient screening of frequently underrecognized conditions, such as the association between increased cardiac uptake on whole-body bone-seeking tracers scintigraphy and ATTR amyloidosis, contributing to identification at earlier stages.</p>
<p>Although bone-seeking tracers scintigraphy does not fully replace all diagnostic methods, Delbarre et al.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> highlighted that when the examination is positive and there is no evidence of monoclonal gammopathy, it may allow definitive noninvasive diagnosis of ATTR cardiomyopathy, particularly in elderly or frail patients in whom myocardial biopsy carries greater risk.</p>
<p>Considering that the diagnosis of cardiac amyloidosis can be established noninvasively through bone-seeking tracers scintigraphy and that visual assessment is inherently subjective and may result in misinterpretation, Spielvogel et al.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> developed an AI system for standardized and reproducible disease screening. The model was trained using a multinational database of <sup>99m</sup>Tc-labeled bone-seeking tracers scintigraphy, encompassing different tracers and scanners. In the Austrian cohort, cross-validation demonstrated an AUC of 1.00 (95% CI: 1.00-1.00). In external validation, results remained high, with an AUC of 0.997 (95% CI: 0.993-0.999) in the United Kingdom, 0.925 (95% CI: 0.871-0.971) in China, and 1.00 (95% CI: 0.999-1.000) in the Italian cohorts. Approximately one decade ago, myocardial biopsy represented the only definitive modality for diagnosing cardiac amyloidosis. The consolidation of bone-seeking tracers scintigraphy constituted a significant advance in this scenario, particularly in the diagnosis of ATTR amyloidosis. The incorporation of AI into this modality further expands its potential by reducing interpretative subjectivity and increasing diagnostic standardization and reliability.</p>
<p>In the aforementioned multicenter study, intense cardiac uptake was automatically and consistently identified across all tracers used in the investigation of cardiac amyloidosis. Additionally, AI-based screening for detection of uptake suggestive of cardiac amyloidosis in patients undergoing whole-body bone-seeking tracers scintigraphy represents a potentially valuable tool for early disease identification and optimization of care pathways. Implementing this strategy may support timely referral for specialized evaluation and enable earlier initiation of disease-modifying therapies, with potential impact on mortality reduction.</p>
</sec>
<sec>
<title>Artificial intelligence in cardiac magnetic resonance evaluation</title>
<p>CMR with late gadolinium enhancement (LGE) is a fundamental method in the investigation of cardiac amyloidosis, given its ability to demonstrate morphological alterations and characteristic enhancement patterns. However, its use may be limited in patients with significant renal impairment, a condition frequently associated with amyloidosis, due to the risks related to contrast administration.</p>
<p>Ma et al.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> investigated the feasibility of diagnosis using non-contrast CMR with native T1 mapping combined with automated radiomic analysis based on AI. The model was trained to recognize specific patterns of amyloid deposition and to indirectly estimate extracellular volume (ECV), a parameter traditionally calculated from pre- and post-gadolinium contrast sequences. In the proposed approach, ECV was accurately estimated through automated identification of myocardial regions of interest. The model achieved an accuracy of 86%, sensitivity of 94%, specificity of 85%, and an AUC of 0.915 in the test set. Unlike bone-seeking tracers scintigraphy, whose main applicability is concentrated on identifying ATTR amyloidosis, non-contrast CMR demonstrated potential for effective diagnosis of cardiac amyloidosis, particularly AL amyloidosis.</p>
<p>In line with this perspective, Nowak et al.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> emphasized that the diagnostic value of CMR derives from its ability to integrate multiple sequences for detailed assessment of myocardial function, edema, inflammation, and fibrosis. ECV allows noninvasive quantification of myocardial amyloid deposition and may influence therapeutic decisions.</p>
<p>Considering that CMR is a reference modality for diagnosing cardiac amyloidosis, Agibetov et al.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> observed that its findings may be nonspecific, especially in centers with lower case volumes. To minimize this risk, they developed a CNN-based algorithm applied to a cohort of 502 patients. Regardless of the deep learning technique employed, models trained with LGE images showed better performance. Fine-tuning of the model resulted in an AUC of 0.96, sensitivity of 94%, and specificity of 90%. Automated classification demonstrated performance comparable to that of human specialists. However, as this was a single-center study, generalization of the results requires caution.</p>
<p>Martini et al.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> also used deep learning for automated analysis of CMR images and estimation of the probability of cardiac amyloidosis. Among the most specific findings, they highlighted the pattern of biventricular pseudo-hypertrophy associated with diffuse transmural LGE. Automated analysis of LGE sequences in the 2C, 4C, and short-axis views was faster and showed accuracy similar to expert assessment, with an AUC of 0.982, positive predictive value of 83%, recall of 95%, and F1-score of 89%.</p>
</sec>
<sec>
<title>Performance of artificial intelligence in the evaluation of genetic testing and biopsies</title>
<p>Another promising field in the application of AI to the diagnosis of cardiac amyloidosis, especially in the AL form, involves systematizing the analysis of genetic tests aimed at identifying somatic mutations in immunoglobulin light chains. Garofalo et al.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> demonstrated, through a machine learning model, an association between somatic mutations acquired during B-cell maturation and the development of cardiac amyloidosis. These mutations affect the structural stability of light chains, favoring protein misfolding and subsequent amyloid deposit formation. The proposed model achieved a sensitivity of 76%, specificity of 82%, and an AUC of 0.87, demonstrating relevant predictive capacity in identifying sequences considered toxic. In addition, the authors highlighted that reversal of these mutations may abolish the toxic phenotype, reinforcing the importance of detailed molecular characterization.</p>
<p>Considering the diversity of pathogenic sequences involved, the use of AI represents an appropriate strategy for organizing and analyzing large volumes of genetic variables, acting as a predictor of toxicity. In this way, the algorithm may identify molecular profiles associated with higher risk of developing cardiac amyloidosis, thereby contributing to risk stratification and potential early diagnosis.</p>
<p>In the field of histopathology, biopsy remains the definitive diagnostic evidence in amyloid cardiomyopathy, despite its invasive nature. In this context, integration between histological techniques and deep learning has also shown promise. Yang et al.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> proposed a neural network-based approach capable of transforming autofluorescence images into images equivalent to those obtained by bright-field and polarized light microscopy, simulating the effect of Congo red staining.</p>
<p>Currently, the diagnostic gold standard is based on the identification of birefringence under cross-polarized light after Congo red staining. However, this process is influenced by technical variability in staining, slide preparation quality, and availability of appropriate equipment, in addition to involving high costs. The model proposed by Yang et al.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> demonstrated that digitally generated images showed quality comparable to conventionally stained slides, with potential cost reduction, lower technical dependence, and improved digital storage of samples, considering that specialized scanners for birefringence capture are not always available.</p>
<p>Thus, although there is growing interest in noninvasive diagnostic methods for cardiac amyloidosis, advances in the application of AI to genetic and histopathological analysis also represent a relevant contribution, improving diagnostic accuracy and standardization of laboratory processes.</p>
</sec>
<sec>
<title>Barriers to implementing artificial intelligence in the medical workflow</title>
<p>The implementation of AI in medical practice has significant potential to increase diagnostic accuracy, optimize care processes, reduce costs, and support clinical decision-making. However, its incorporation into the workflow faces multifactorial challenges that can be grouped into technical, ethical, organizational, and human dimensions.</p>
<p>From a technical perspective, AI models depend on structured, complete, and standardized datasets. However, many health care systems still operate with fragmented, inconsistent, or incomplete records, which compromises proper training and the generalizability of algorithms. In addition, historically biased data may perpetuate health care disparities, resulting in inappropriate recommendations for certain population groups. Interoperability among different information systems also represents a relevant challenge, hindering seamless integration of AI into established clinical environments.</p>
<p>From an ethical and legal standpoint, questions arise regarding accountability in cases of clinical error involving algorithmic recommendations. Defining responsibility among developers, institutions, and professionals remains complex. This is compounded by concerns about data privacy, security, and governance, especially when there is interinstitutional data sharing for model training or validation.</p>
<p>At the organizational level, adoption of AI-based tools requires efficient integration into care workflows. Solutions that add steps to the process or disrupt established routines tend to generate resistance and operational burden. In addition, physicians, nurses, and other professionals must be trained to critically interpret the recommendations provided by these systems, using them as support rather than as a substitute for clinical judgment. Implementation also requires investment in technological infrastructure, maintenance, and continuous model updating, which may represent a financial barrier for certain institutions.</p>
<p>Finally, the human dimension involves aspects related to professional acceptance and patient trust. Some professionals may express distrust toward the technology or perceive AI as a threat to their clinical role. The so-called &quot;black box&quot; nature of algorithms, in which the decision-making process is not fully transparent, may reduce trust in the tool and hinder its incorporation into clinical practice. From the patient&apos;s perspective, trust in decisions influenced by algorithms is not yet universal. Conversely, there is a risk of excessive reliance on AI by professionals, which may compromise independent clinical reasoning if a critical and reflective stance is not maintained.</p>
</sec>
</sec>
<sec sec-type="conclusions">
<title>Conclusion</title>
<p>Based on the findings of this review, AI emerges as a promising tool for optimizing the screening and diagnosis of cardiac amyloidosis. Its application across different diagnostic modalities demonstrates potential to accelerate disease identification, contribute to greater diagnostic accuracy, and consequently support improved clinical outcomes.</p>
<p>The high capacity for processing and analyzing large volumes of data enables AI to recognize complex patterns, expand its ability to generalize, provided it is trained on robust and representative datasets, and assist in the early detection of cardiac amyloidosis. Furthermore, using automated models may reduce the subjectivity of human interpretation, minimize the need for invasive procedures in certain contexts, and rationalize the use of health care resources.</p>
<p>However, despite the advances observed, the consolidation of AI in clinical practice requires continuous model refinement, external validation in diverse populations, and efficient integration into care workflows. Strategic implementation planning, training of health professionals, ethical governance in data management, and ongoing monitoring of algorithmic performance are equally essential.</p>
</sec>
</body>
<back>
<fn-group>
<fn fn-type="financial-disclosure" id="fn1"><label>Sources of Funding</label>
<p>There were no external funding sources for this study.</p></fn>
<fn fn-type="other" id="fn2"><label>Study Association</label>
<p>This study is not associated with any thesis or dissertation work.</p></fn>
<fn fn-type="other" id="fn3"><label>Ethics Approval and Consent to Participate</label>
<p>This article does not contain any studies with human participants or animals performed by any of the authors.</p></fn>
<fn fn-type="other" id="fn4"><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">
<title>Availability of Research Data</title>
<p>The underlying content of the research text is contained within the manuscript.</p>
</sec>
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<role>Concepção e desenho da pesquisa</role>
<role>análise e interpretação dos dados</role>
<role>redação do manuscrito e revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
</contrib>
<aff id="aff2">
<label>1</label>
<addr-line>
<named-content content-type="city">João Pessoa</named-content>
<named-content content-type="state">PB</named-content>
</addr-line>
<country country="BR">Brasil</country>
<institution content-type="original">Universidade Federal da Paraíba, João Pessoa, PB – Brasil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c2"><label>Correspondência:</label> <bold>Nilson Batista Lemos</bold> • Universidade Federal da Paraíba. Campus I Lot., Cidade Universitaria. CEP: <postal-code>58051-900</postal-code>. João Pessoa, PB – Brasil E-mail: <email>nilsonlemos18@gmail.com</email></corresp>
<fn fn-type="coi-statement"><label>Potencial Conflito de Interesse</label>
<p>Declaro não haver conflito de interesses pertinentes.</p></fn>
<fn fn-type="edited-by"><label>Editor responsável pela revisão:</label><p>Marcelo Tavares</p></fn>
</author-notes>
<abstract>
<title>Resumo</title>
<sec>
<title>Fundamento:</title>
<p>A amiloidose cardíaca é uma forma rara de cardiomiopatia infiltrativa caracterizada pela deposição de proteínas no miocárdio, resultando em aumento da espessura parietal, comprometimento da função ventricular e possível progressão para insuficiência cardíaca. O diagnóstico é desafiador devido à baixa prevalência da doença e à inespecificidade das manifestações clínicas. Nesse cenário, a aplicação da inteligência artificial (IA) à análise de exames médicos surge como estratégia promissora para detecção precoce, diagnóstico mais preciso e início oportuno do tratamento.</p>
</sec>
<sec>
<title>Métodos:</title>
<p>Realizou-se revisão integrativa da literatura sobre o uso da IA no diagnóstico da amiloidose cardíaca. Foram pesquisados artigos publicados entre 2019 e 2024 nas bases de dados PubMed, Scopus, Web of Science, Embase e Cochrane Library.</p>
</sec>
<sec>
<title>Resultados:</title>
<p>Dos 420 artigos inicialmente identificados, 21 atenderam aos critérios de elegibilidade e foram incluídos na análise final. Observou-se predomínio de estudos observacionais retrospectivos com aplicação de modelos de aprendizado de máquina. Entre as modalidades diagnósticas avaliadas em associação com IA, o eletrocardiograma e o ecocardiograma foram os exames mais frequentemente estudados.</p>
</sec>
<sec>
<title>Conclusão:</title>
<p>A IA demonstra elevado potencial para aprimorar o rastreio e o diagnóstico da amiloidose cardíaca quando aplicada à análise de exames clínicos e de imagem. Os achados desta revisão indicam que a IA pode acelerar o processo diagnóstico, reduzir a necessidade de procedimentos invasivos e otimizar o uso de recursos em saúde. Entretanto, para ampliar sua integração à prática clínica e sua capacidade de generalização, são necessários aprimoramentos adicionais nos modelos e validações em populações mais diversas.</p>
</sec>
</abstract>
<kwd-group xml:lang="pt">
<title>Palavras-chave:</title>
<kwd>Amiloidose</kwd>
<kwd>Inteligência Artificial</kwd>
<kwd>Diagnóstico</kwd>
</kwd-group>
<funding-group>
<funding-statement><bold>Fontes de Financiamento</bold>: O presente estudo não teve fontes de financiamento externas.</funding-statement>
</funding-group>
</front-stub>
<body>
<fig id="f3">
<graphic xlink:href="2675-312X-abcic-39-1-e20260016-gf01-pt.tif"/>
</fig>
<sec sec-type="intro">
<title>Introdução</title>
<p>A amiloidose é um termo genérico utilizado para descrever a deposição extracelular de fibrilas formadas por subunidades proteicas de baixo peso molecular, derivadas de diferentes proteínas precursoras. Os depósitos amiloides podem resultar em ampla variedade de manifestações clínicas, que variam conforme o tipo de proteína envolvida, a quantidade depositada e a localização tecidual. Na gênese desses depósitos, peptídeos inicialmente solúveis sofrem alterações conformacionais, adquirindo predominantemente uma estrutura de folha beta-pregueada antiparalela, o que favorece seu empilhamento em fibrilas torcidas.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
<p>Existem dezenas de formas sistêmicas e localizadas de amiloidose. Entre elas, quatro proteínas precursoras podem originar depósitos tanto localizados quanto sistêmicos. As principais formas sistêmicas são a amiloidose de cadeia leve de imunoglobulina (AL, em inglês) e a amiloidose por transtirretina (ATTR, em inglês). Essas formas são nomeadas de acordo com a proteína precursora do depósito amiloide (AL ou ATTR) e são responsáveis por aproximadamente 95% dos casos de amiloidose cardíaca. As demais formas correspondem a outros subtipos de amiloidose, igualmente relevantes do ponto de vista clínico.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
<p>A amiloidose por ATTR caracteriza-se pelo dobramento incorreto e subsequente deposição da transtirretina, proteína responsável pelo transporte do hormônio tireoidiano e da vitamina A. Pode apresentar-se na forma selvagem ou hereditária.<sup><xref ref-type="bibr" rid="B2">2</xref>-<xref ref-type="bibr" rid="B4">4</xref></sup> Similarmente, a amiloidose AL decorre do acúmulo de cadeias leves de imunoglobulinas mal dobradas, produzidas por células plasmáticas associadas a discrasias.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
<p>No contexto da amiloidose cardíaca, trata-se de uma forma rara de cardiomiopatia progressiva, cuja prevalência populacional ainda não está bem estabelecida.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> A doença é causada pela deposição miocárdica de proteínas amiloides mal dobradas, resultando em cardiomiopatia restritiva, com possível progressão para insuficiência cardíaca, distúrbios do sistema de condução e morte cardíaca.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> Pode manifestar-se com sinais e sintomas cardiovasculares ou ser diagnosticada durante a investigação de manifestações extracardíacas da doença.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> Devido ao fenótipo clínico heterogêneo e às manifestações frequentemente inespecíficas, o diagnóstico e o manejo tendem a ocorrer de forma tardia.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
<p>No que se refere à abordagem diagnóstica da amiloidose cardíaca, é fundamental reconhecer cenários clínicos e alterações em exames complementares que indiquem a necessidade de investigação. Entretanto, o diagnóstico é desafiador, especialmente por se tratar de doença frequentemente indolente, cujos sintomas podem se sobrepor aos de cardiopatias mais prevalentes.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> Dependendo do contexto clínico e da disponibilidade de recursos, diversas ferramentas podem ser empregadas, incluindo eletrocardiograma (ECG), ecocardiograma, ressonância magnética cardíaca (RMC), cintilografia com traçadores ósseos, pesquisa de proteína monoclonal por imunofixação e biópsia do tecido acometido. Cada método apresenta características próprias e diferentes níveis de acurácia diagnóstica (<xref ref-type="fig" rid="f3">Figura Central</xref>).</p>
<p>Alguns achados podem aumentar a suspeita clínica de amiloidose cardíaca, como a discordância entre o aumento da espessura da parede do ventrículo esquerdo (VE) e a baixa voltagem do QRS, hipertrofia inexplicada do VE, estenose aórtica de baixo fluxo e baixo gradiente, preservação apical relativa da deformação longitudinal, padrão de realce tardio subendocárdico difuso e circunferencial do VE na RMC e avidez miocárdica por traçadores ósseos na cintilografia com traçadores ósseos.</p>
<p>Apesar da diversidade de métodos diagnósticos disponíveis, a amiloidose cardíaca permanece subdiagnosticada,<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B5">5</xref>-<xref ref-type="bibr" rid="B7">7</xref></sup> o que implica importantes repercussões na qualidade de vida dos pacientes. Paralelamente, o desenvolvimento de terapias capazes de melhorar desfechos clínicos tem impulsionado a busca por estratégias que ampliem a taxa de diagnóstico. Essas intervenções podem reduzir ou estabilizar a deposição proteica, com consequente diminuição do risco relativo de hospitalizações, da morbidade e da mortalidade associadas à doença.</p>
<p>Diante da necessidade de detecção precoce da amiloidose cardíaca, torna-se essencial o desenvolvimento de mecanismos que otimizem o rastreio e o diagnóstico, com menores custos e riscos.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Nesse contexto, esta revisão tem como objetivo apresentar os principais avanços na detecção da doença, com ênfase em ferramentas tecnológicas promissoras no âmbito da medicina diagnóstica, especialmente a inteligência artificial (IA).</p>
<p>A IA constitui um ramo da ciência da computação dedicado ao desenvolvimento de sistemas capazes de executar tarefas que simulam funções cognitivas humanas, como tomada de decisão e raciocínio complexo. No campo do diagnóstico médico, esses sistemas são treinados por meio de técnicas de aprendizado de máquina, nas quais grandes volumes de dados, frequentemente imagens, são utilizados para o reconhecimento de padrões. Entre as abordagens mais empregadas destacam-se as redes neurais convolucionais (CNNs, na sigla em inglês), compostas por múltiplas camadas que extraem características progressivamente mais complexas dos dados analisados, permitindo a identificação automatizada de padrões em imagens e outros tipos de informação. De modo geral, quanto maior e mais representativo o conjunto de dados utilizado no treinamento, maior tende a ser a precisão do modelo.</p>
<p>A incorporação da IA à prática médica possibilita aprimorar o rastreio de doenças raras e aumentar a acurácia diagnóstica. Nesse cenário, a IA mostra-se particularmente promissora para doenças raras, frequentemente pouco reconhecidas na prática clínica. Sistemas automatizados podem integrar múltiplos sinais, sintomas e achados complementares, contribuindo para direcionar o raciocínio clínico. Assim, habilidades centrais na medicina, como o reconhecimento de padrões, vêm sendo incorporadas a modelos computacionais com o objetivo de ampliar a confiabilidade diagnóstica e apoiar a tomada de decisão no cotidiano médico.</p>
<p>Diversos estudos têm investigado a aplicabilidade da IA no diagnóstico precoce da amiloidose cardíaca. Entre as abordagens mais recentes destacam-se a integração da IA a métodos de imagem, como tomografia por emissão de fóton único (SPECT), cintilografia com traçadores ósseos e RMC, bem como sua aplicação na análise automatizada de ECGs, dados genéticos e perfis fenotípicos de alterações cardíacas. Esses aspectos serão discutidos ao longo desta revisão.</p>
</sec>
<sec sec-type="methods">
<title>Métodos</title>
<p>O presente estudo caracteriza-se como uma revisão integrativa de literatura, com o objetivo de analisar criticamente o uso da IA no diagnóstico da amiloidose cardíaca. A condução da revisão seguiu seis etapas metodológicas: i) definição da pergunta de pesquisa; ii) estabelecimento dos critérios de inclusão e seleção da amostra; iii) identificação dos estudos pré-selecionados e selecionados; iv) organização e representação dos estudos incluídos; v) análise crítica dos dados; e vi) síntese do conhecimento disponível.</p>
<p>As buscas foram realizadas nas bases de dados PubMed, Scopus, Web of Science, Embase e Cochrane Library. A estratégia de busca foi elaborada a partir dos descritores &quot;artificial intelligence&quot;, &quot;amyloidosis&quot; e &quot;diagnosis&quot;, presentes no <italic>Medical Subject Headings</italic> e no <italic>Embase Subject Headings</italic>, combinados por meio do operador booleano AND.</p>
<p>Foram incluídos estudos originais e metanálises publicados entre 2019 e 2024 que avaliaram a aplicação da IA no diagnóstico da amiloidose cardíaca. Foram excluídos artigos que não atenderam aos critérios de inclusão, bem como revisões narrativas, relatos de caso, editoriais e estudos com metodologia considerada inadequada.</p>
<p>Após a seleção dos artigos, procedeu-se à avaliação da qualidade metodológica, com o objetivo de assegurar maior rigor na interpretação dos achados e robustez às conclusões. Para essa etapa, utilizou-se a ferramenta de avaliação crítica do JBI, que contempla critérios específicos conforme o delineamento do estudo, incluindo aspectos relacionados à amostra, metodologia, análise de dados, controle de vieses e considerações éticas. A classificação da qualidade baseia-se na proporção de respostas afirmativas aos critérios avaliados, permitindo a comparação entre estudos e a análise crítica de seus resultados.</p>
</sec>
<sec sec-type="results">
<title>Resultados</title>
<p>A estratégia de busca resultou em 420 artigos, distribuídos da seguinte forma: 124 identificados no PubMed, 61 na Web of Science, 84 no Scopus, 147 no Embase e 4 na Cochrane Library. Após a remoção de 192 estudos duplicados, permaneceram 228 artigos para triagem.</p>
<p>A leitura de títulos e resumos resultou na seleção de 43 estudos para avaliação na íntegra. Após a aplicação dos critérios de elegibilidade, 21 artigos foram incluídos na análise final (<xref ref-type="fig" rid="f4">Figura 1</xref>).</p>
<fig id="f4">
<label>Figura 1</label>
<caption><title>Fluxograma do processo de seleção dos estudos incluídos na revisão integrativa.</title></caption>
<graphic xlink:href="2675-312X-abcic-39-1-e20260016-gf02-pt.tif"/>
</fig>
<p>Quanto à avaliação metodológica, segundo os critérios do JBI, a maioria dos estudos foi classificada com qualidade metodológica entre boa e excelente, com pontuação variando de 6 a 8 pontos. Entre os principais fatores que contribuíram para essa classificação destacam-se o emprego de métricas estatísticas robustas e a utilização de validação cruzada nos modelos de IA desenvolvidos.</p>
<p>Como limitações, observou-se a ausência de confirmação diagnóstica por padrão-ouro da amiloidose cardíaca em parte dos estudos, bem como a escassez de validação externa dos modelos propostos, o que limita a generalização dos achados. Os resultados detalhados da avaliação metodológica estão apresentados na <xref ref-type="table" rid="t2">Tabela 1</xref>.</p>
<table-wrap id="t2">
<label>Tabela 1</label>
<caption><title>Características metodológicas e avaliação da qualidade dos estudos incluídos</title></caption>
<table frame="hsides" rules="groups">
<colgroup width="20%">
<col/>
<col/>
<col/>
<col/>
<col/>
</colgroup>
<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
<tr style="background-color:#C58874">
<th align="left" valign="middle">Nº</th>
<th align="center" valign="middle">Estudo (autor/ano)</th>
<th align="center" valign="middle">Delineamento</th>
<th align="center" valign="middle">Pontuação (JBI/8)</th>
<th align="center" valign="middle">Avaliação metodológica</th>
</tr>
</thead>
<tbody style="border-bottom: thin solid; border-color: #000000">
<tr>
<td align="left" valign="middle">1</td>
<td align="center" valign="middle">Agibetov et al. (2021)<sup><xref ref-type="bibr" rid="B18">18</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo com ressonância magnética cardíaca e aplicação de aprendizado de máquina</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">Alta qualidade</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">2</td>
<td align="center" valign="middle">Barbieri et al. (2024)<sup><xref ref-type="bibr" rid="B11">11</xref></sup></td>
<td align="center" valign="middle">Estudo com ecocardiograma transtorácico tridimensional automatizado associado a aprendizado de máquina</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">Alta qualidade</td>
</tr>
<tr>
<td align="left" valign="middle">3</td>
<td align="center" valign="middle">Castaño et al. (2024)<sup><xref ref-type="bibr" rid="B9">9</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo caso-controle com aplicação de aprendizado de máquina</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">Alta qualidade</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">4</td>
<td align="center" valign="middle">Cotella et al. (2023)<sup><xref ref-type="bibr" rid="B2">2</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo com ecocardiograma e aplicação de aprendizado de máquina</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">Alta qualidade</td>
</tr>
<tr>
<td align="left" valign="middle">5</td>
<td align="center" valign="middle">Delbarre et al. (2023)<sup><xref ref-type="bibr" rid="B14">14</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo multicêntrico com cintilografia com traçadores ósseos analisada por aprendizado de máquina</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">Excelente</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">6</td>
<td align="center" valign="middle">Eckstein et al. (2022)<sup><xref ref-type="bibr" rid="B7">7</xref></sup></td>
<td align="center" valign="middle">Estudo observacional de coorte com ecocardiograma e uso de aprendizado de máquina</td>
<td align="center" valign="middle">6</td>
<td align="center" valign="middle">Boa qualidade</td>
</tr>
<tr>
<td align="left" valign="middle">7</td>
<td align="center" valign="middle">Garofalo et al. (2021)<sup><xref ref-type="bibr" rid="B20">20</xref></sup></td>
<td align="center" valign="middle">Estudo computacional preditivo com validação experimental focado em avaliação genética por aprendizado de máquina</td>
<td align="center" valign="middle">6</td>
<td align="center" valign="middle">Boa qualidade</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">8</td>
<td align="center" valign="middle">Goto et al. (2021)<sup><xref ref-type="bibr" rid="B3">3</xref></sup></td>
<td align="center" valign="middle">Estudo observacional multicêntrico com uso de eletrocardiograma e ecocardiograma</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">Excelente</td>
</tr>
<tr>
<td align="left" valign="middle">9</td>
<td align="center" valign="middle">Harmon et al. (2023)<sup><xref ref-type="bibr" rid="B10">10</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo com eletrocardiograma e aplicação de aprendizado de máquina</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">Alta qualidade</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">10</td>
<td align="center" valign="middle">Huda et al. (2021)<sup><xref ref-type="bibr" rid="B8">8</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo com aplicação de aprendizado de máquina</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">Alta qualidade</td>
</tr>
<tr>
<td align="left" valign="middle">11</td>
<td align="center" valign="middle">Ma et al. (2024)<sup><xref ref-type="bibr" rid="B16">16</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo com ressonância magnética cardíaca sem contraste e uso de aprendizado de máquina</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">Alta qualidade</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">12</td>
<td align="center" valign="middle">Martini et al. (2020)<sup><xref ref-type="bibr" rid="B19">19</xref></sup></td>
<td align="center" valign="middle">Estudo observacional prospectivo com ressonância magnética cardíaca e aplicação de aprendizado de máquina</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">Excelente</td>
</tr>
<tr>
<td align="left" valign="middle">13</td>
<td align="center" valign="middle">Miller et al. (2024)<sup><xref ref-type="bibr" rid="B13">13</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo com tomografia por emissão de pósitrons e segmentação automatizada</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">Excelente</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">14</td>
<td align="center" valign="middle">Nowak et al. (2024)<sup><xref ref-type="bibr" rid="B17">17</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo com ressonância magnética cardíaca, mapeamento T1 e uso de aprendizado de máquina</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">Alta qualidade</td>
</tr>
<tr>
<td align="left" valign="middle">15</td>
<td align="center" valign="middle">Santarelli et al. (2021)<sup><xref ref-type="bibr" rid="B12">12</xref></sup></td>
<td align="center" valign="middle">Estudo observacional prospectivo com tomografia por emissão de pósitrons e aplicação de aprendizado de máquina</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">Alta qualidade</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">16</td>
<td align="center" valign="middle">Schrutka et al. (2022)<sup><xref ref-type="bibr" rid="B6">6</xref></sup></td>
<td align="center" valign="middle">Estudo observacional prospectivo caso-controle com aplicação de aprendizado de máquina</td>
<td align="center" valign="middle">6</td>
<td align="center" valign="middle">Boa qualidade</td>
</tr>
<tr>
<td align="left" valign="middle">17</td>
<td align="center" valign="middle">Shiri et al. (2025)<sup><xref ref-type="bibr" rid="B4">4</xref></sup></td>
<td align="center" valign="middle">Estudo observacional prospectivo de coorte única com aplicação de aprendizado de máquina</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">Alta qualidade</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">18</td>
<td align="center" valign="middle">Spielvogel et al. (2024)<sup><xref ref-type="bibr" rid="B15">15</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo multicêntrico com cintilografia com traçadores ósseos e uso de aprendizado de máquina</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">Excelente</td>
</tr>
<tr>
<td align="left" valign="middle">19</td>
<td align="center" valign="middle">Vrudhula et al. (2024)<sup><xref ref-type="bibr" rid="B5">5</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo com aplicação de aprendizado de máquina</td>
<td align="center" valign="middle">6</td>
<td align="center" valign="middle">Boa qualidade</td>
</tr>
<tr style="background-color:#E8CCBF">
<td align="left" valign="middle">20</td>
<td align="center" valign="middle">Yang et al. (2024)<sup><xref ref-type="bibr" rid="B21">21</xref></sup></td>
<td align="center" valign="middle">Estudo observacional com análise histopatológica digital utilizando rede neural e autofluorescência</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">Alta qualidade</td>
</tr>
<tr>
<td align="left" valign="middle">21</td>
<td align="center" valign="middle">Zhang et al. (2023)<sup><xref ref-type="bibr" rid="B1">1</xref></sup></td>
<td align="center" valign="middle">Estudo observacional retrospectivo com ecocardiograma e aplicação de aprendizado de máquina</td>
<td align="center" valign="middle">6</td>
<td align="center" valign="middle">Boa qualidade</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec sec-type="discussion">
<title>Discussão</title>
<p>O uso da IA como ferramenta de apoio ao diagnóstico de doenças raras, como a amiloidose cardíaca, tem sido considerado promissor, especialmente no contexto de patologias com elevada heterogeneidade clínica e frequentemente sub-reconhecidas por médicos generalistas. A identificação precoce da doença pode modificar sua história natural e melhorar o prognóstico. Nesse cenário, esta revisão buscou enfatizar o potencial das ferramentas diagnósticas já consolidadas para a avaliação da amiloidose cardíaca quando associadas a sistemas baseados em aprendizado de máquina, abordagem contemplada por todos os estudos incluídos.</p>
<p>Com o objetivo de organizar a análise dos achados, o desempenho da IA será discutido de acordo com as diferentes modalidades diagnósticas empregadas no rastreio e na avaliação da amiloidose cardíaca.</p>
<sec>
<title>Desempenho da inteligência artificial na avaliação de dados de prontuários e exames laboratoriais</title>
<p>Entre as estratégias de rastreio da cardiopatia amiloide, destaca-se a utilização de dados extraídos de prontuários eletrônicos de pacientes com insuficiência cardíaca (IC) com fração de ejeção preservada (ICFEp). Com o objetivo de diferenciar etiologia amiloide, especialmente do amiloidose por ATTR do tipo selvagem (ATTRwt), de etiologia não amiloide, Huda et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> coletou dados de prontuário eletrônico e desenvolveu uma IA capaz de realizar a triagem e identificação de pacientes com amiloidose por ATTRwt. O sistema apresentou área sob a curva (AUC, em inglês) característica de operação do receptor de 0,80. O desempenho foi sustentado pela identificação de comorbidades mais prevalentes no grupo com etiologia amiloide, como fibrilação atrial e doença renal crônica, e no grupo não amiloide, como hipertensão arterial sistêmica, diabetes melito, obesidade e doença arterial coronariana, utilizadas como variáveis preditoras.</p>
<p>Posteriormente, Castaño et al.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> aprimoraram o modelo ao direcionar a análise para 11 fenótipos principais associados à amiloidose cardíaca, incluindo síndrome do túnel do carpo e arritmias. O modelo apresentou precisão (74%), sensibilidade (77%) e especificidade (72%), com AUC de 0,82. Embora tenha havido discreta redução em alguns parâmetros de desempenho, o modelo foi simplificado em termos de programação, favorecendo sua implementação em ambientes hospitalares e ampliando o potencial de rastreio populacional.</p>
<p>Os estudos de Huda et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> e Castaño et al.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> demonstram a viabilidade de triagem automatizada por meio da extração sistematizada de dados clínicos, processo que seria oneroso e operacionalmente complexo se realizado manualmente. Embora tais modelos estejam limitados à qualidade dos registros codificados pela Classificação Internacional de Doenças e aos fenótipos documentados, sem integração direta de exames laboratoriais ou de imagem para tipificação definitiva, configuram ferramentas relevantes para rastreio em larga escala, direcionando pacientes com maior probabilidade para investigação complementar.</p>
<p>Adicionalmente, fenótipos reconhecidos pelo modelo, como síndrome do túnel do carpo, podem preceder o desenvolvimento de IC, o que sugere potencial aplicação da IA em estágios pré-clínicos, com implicações na identificação precoce da amiloidose por ATTR.</p>
</sec>
<sec>
<title>Desempenho da inteligência artificial na avaliação eletrocardiográfica</title>
<p>A aplicação da IA na análise de ECGs tem se destacado como estratégia de triagem, considerando que se trata de exame amplamente disponível, de baixo custo e não invasivo.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> A etapa de validação dos modelos constitui fase fundamental no desenvolvimento dessas ferramentas, pois envolve o teste de múltiplas variáveis em diferentes populações.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
<p>Harmon et al.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> desenvolveram um algoritmo aplicável a populações diversas, incluindo diferentes raças e sexos. O modelo apresentou AUC de 0,84 (intervalo de confiança [IC] de 95%: 0,82-0,86), mantendo desempenho consistente entre subgrupos, com exceção da população hispânica, possivelmente sub-representada na amostra. O algoritmo apresentou melhor desempenho em ECGs com baixa voltagem e padrões compatíveis com infarto prévio, e menor desempenho em bloqueio de ramo esquerdo e hipertrofia do VE. Esses achados sugerem necessidade de maior diversidade amostral, sem invalidar o uso da ferramenta como método de triagem.</p>
<p>Vrudhula et al.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> avaliaram aproximadamente 1,3 milhão de ECGs provenientes de 341.989 pacientes. Os diferentes modelos testados apresentaram AUC variando de 0,660 (IC 95%: 0,642-0,736) a 0,898 (IC 95%: 0,868-0,924), demonstrando potencial relevante para rastreio e indicação de investigação complementar. Entretanto, ressalta-se que, diante da raridade e do subdiagnóstico da amiloidose cardíaca, os modelos frequentemente são treinados com número limitado de casos confirmados.</p>
<p>De forma semelhante, Goto et al.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> relataram desempenho expressivo, com estatística C de 0,91 (IC 95%: 0,90-0,93) no conjunto de teste do Brigham and Women&apos;s Hospital, 0,85 (0,82-0,87) no Massachusetts General Hospital e 0,86 (0,83-0,88) na University of California, San Francisco. Contudo, os autores enfatizam que características isoladas do ECG não apresentam sensibilidade ou especificidade suficientes para uso como heurísticas independentes, sendo recomendada sua integração com outras variáveis clínicas e diagnósticas para otimização do modelo.</p>
<p>Schrutka et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> também reforçam que o modelo proposto pode auxiliar na suspeição de amiloidose cardíaca mesmo na ausência de métodos avançados de imagem. No referido estudo, foram avaliados 20 pacientes com amiloidose cardíaca por transtirretina, 11 com ICFEp, 30 com amiloidose cardíaca e 50 com outras etiologias de IC. A presença de padrão de ECG de baixa voltagem associada ao aumento da espessura da parede do VE foi altamente sugestiva de amiloidose cardíaca, o que permitiu sua diferenciação em relação à cardiomiopatia hipertensiva ou hipertrófica. Na análise dos padrões de ECG, observou-se que o padrão 1 esteve presente em 78% dos pacientes com amiloidose por AL e em 58% daqueles com amiloidose por ATTR (p = 0,009), enquanto o padrão 2 foi identificado em 7% dos casos de amiloidose por AL e em 23% dos casos de amiloidose por ATTR (p = 0,006). A ausência de padrão específico foi observada em 16% dos pacientes com amiloidose por AL e em 18% dos pacientes com amiloidose por ATTR (p = 0,620).</p>
</sec>
<sec>
<title>Desempenho da inteligência artificial na avaliação ecocardiográfica</title>
<p>Considerando a versatilidade da ecocardiografia e seu papel central na investigação diagnóstica da amiloidose cardíaca, o desenvolvimento de modelos de IA capazes de reduzir a variabilidade operacional e aprimorar a acurácia diagnóstica mostra-se relevante.</p>
<p>Xiaofeng Zhang et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> observaram que ainda existem poucos estudos sobre análise de textura miocárdica baseada em ecocardiografia e que a avaliação visual humana apresenta limitações para caracterização dessas alterações. Com base em ecocardiogramas transtorácicos, os autores desenvolveram quatro algoritmos de aprendizado de máquina para diferenciar amiloidose cardíaca de outras cardiomiopatias: floresta aleatória (RF, em inglês), máquina de vetor de suporte (SVM, em inglês), regressão logística (LR, em inglês) e árvores de decisão impulsionadas por gradiente (GBDT, em inglês).</p>
<p>Na população analisada, todos os modelos conseguiram distinguir de forma eficaz casos de amiloidose cardíaca de doenças não amiloides. O modelo de LR apresentou o melhor desempenho diagnóstico, superando o método ultrassonográfico tradicional (AUC: RF 0,77; SVM 0,81; LR 0,81; GBDT 0,71). Os autores propuseram, portanto, a aplicação dessa ferramenta como método diagnóstico não invasivo para amiloidose miocárdica. Entretanto, o número relativamente pequeno de casos de amiloidose cardíaca pode ter limitado a sensibilidade do modelo para discriminação entre os grupos.</p>
<p>Cotella et al.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> desenvolveram um modelo de IA voltado à avaliação automatizada da fração de ejeção do VE (FEVE) e do <italic>strain</italic> longitudinal global (SLG), parâmetros centrais no diagnóstico da amiloidose cardíaca. Os autores justificaram a incorporação da IA com base no fato de que as medições manuais são demoradas e apresentam variabilidade inter e intraobservador significativa, o que pode comprometer a precisão diagnóstica e influenciar decisões terapêuticas. O estudo demonstrou que as medições automatizadas e quantitativas de FEVE e SLG apresentaram alta precisão e permitiram a detecção sensível e específica de anormalidades quando comparadas à análise manual convencional, tanto em exames realizados antes do diagnóstico de amiloidose cardíaca quanto no momento do diagnóstico. Não foram observadas diferenças estatisticamente significativas entre os valores obtidos pelos dois métodos no período pré-diagnóstico (FEVE: p = 0,791; SLG: p = 0,105) nem no momento do diagnóstico (FEVE: p = 0,463; SLG: p = 0,722). Além disso, verificou-se forte correlação entre as medições automatizadas e manuais nos ecocardiogramas realizados antes do diagnóstico (r = 0,78 para FEVE; r = 0,83 para SLG) e no diagnóstico estabelecido (r = 0,74 para FEVE; r = 0,80 para SLG).</p>
<p>Goto et al.,<sup><xref ref-type="bibr" rid="B3">3</xref></sup> embora reconheçam que modelos baseados em ECG apresentam resultados encorajadores, ressaltam que seu desempenho pode não ser suficiente para o diagnóstico de doenças de baixa prevalência. Nesse contexto, o modelo ecocardiográfico desenvolvido pelos autores demonstrou maior precisão preditiva quando comparado ao modelo baseado em ECG. As estatísticas C variaram de 0,85-0,91 para o ECG e de 0,89-1,00 para a ecocardiografia. Além disso, na análise por subtipos, o modelo apresentou desempenho superior na identificação da amiloidose por ATTR.</p>
<p>Em uma população mais específica, Shiri et al.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> avaliaram o uso de aprendizado de máquina para detecção de amiloidose por ATTR em pacientes com estenose aórtica grave. Embora diferentes modalidades diagnósticas sejam úteis na avaliação inicial desses pacientes, elas não são específicas para amiloidose por ATTR. Frequentemente, o diagnóstico definitivo de cardiomiopatia por ATTR depende de confirmação histopatológica ou da identificação de mutação no gene <italic>TTR</italic>, associada à evidência de captação miocárdica significativa na cintilografia com traçadores ósseos. Considerando o custo elevado de testes genéticos e da cintilografia com traçadores ósseos, especialmente nesse grupo de pacientes, os autores desenvolveram modelo não invasivo e potencialmente custo-efetivo, baseado em dados clínicos e ecocardiográficos de rotina. O desempenho foi satisfatório quando comparado a variáveis clínicas, laboratoriais e de imagem intervencionista, com AUC de 0,79, sensibilidade de 0,80 e especificidade de 0,78.</p>
<p>Eckstein et al.,<sup><xref ref-type="bibr" rid="B7">7</xref></sup> fundamentados em evidências de que a análise da deformação miocárdica fornece valor discriminativo em múltiplas câmaras cardíacas, desenvolveram modelo supervisionado capaz de diferenciar amiloidose cardíaca de cardiomiopatia hipertrófica e de indivíduos saudáveis. O sistema apresentou desempenho elevado (AUC = 0,996; precisão = 94%; sensibilidade = 100%; <italic>F1-score</italic> = 97%), indicando que a análise automatizada da deformação e função cardíaca multicâmara pode atuar como ferramenta de suporte à decisão clínica, inclusive sem necessidade de contraste.</p>
<p>Com a evolução tecnológica dos métodos de imagem cardiovascular, novas abordagens têm sido propostas para o rastreio de cardiopatias infiltrativas. Nesse contexto, Barbieri et al.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> desenvolveram modelo baseado em ecocardiograma transtorácico tridimensional (ETT-3D) associado à IA, com o objetivo de diferenciar diversos fenótipos de hipertrofia cardíaca, incluindo amiloidose cardíaca. O método propõe reformulação da análise da fração de ejeção, tradicionalmente baseada em RMC, por meio da utilização do ETT-3D integrado a sistema de IA. A aquisição tridimensional permitiu análise mais detalhada e precisa do volume do VE, possibilitando cálculo mais acurado da fração de ejeção, definida como a razão entre o volume sistólico e o volume diastólico final, refletindo a capacidade contrátil miocárdica. Essa abordagem fornece informações mais precisas sobre encurtamento e espessura da parede miocárdica, aspectos fundamentais para o reconhecimento de cardiomiopatias infiltrativas. No ecocardiograma bidimensional convencional, o aumento da espessura parietal pode mascarar redução do encurtamento miocárdico, resultando em fração de ejeção aparentemente preservada. No contexto da investigação etiológica da ICFEp, o modelo mostrou-se promissor, apresentando fração de ejeção mais elevada em pacientes com cardiomiopatia hipertrófica e com amiloidose cardíaca, sendo que estes últimos exibiram valores proporcionalmente ainda maiores. O desempenho diagnóstico foi consistente, com sensibilidade de 87%, especificidade de 100% e AUC de 0,959, reforçando o potencial da integração entre ETT-3D e IA na diferenciação fenotípica da hipertrofia miocárdica.</p>
</sec>
<sec>
<title>Inteligência artificial na avaliação da tomografia por emissão de pósitrons</title>
<p>De maneira semelhante a outras modalidades de imagem, a PET-CT tem sido aprimorada com o objetivo de tornar o processo diagnóstico da amiloidose cardíaca menos invasivo e mais preciso. Nesse contexto, destacam-se modelos baseados em <italic>deep learning</italic> voltados ao reconhecimento automatizado de padrões de imagem relacionados à deposição amiloide.</p>
<p>Santarelli et al.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> desenvolveram modelo com o objetivo de identificar, de forma rápida, precoce e específica, a presença de amiloidose cardíaca e seus subtipos. O sistema demonstrou desempenho superior ao da análise realizada por especialista com mais de 10 anos de experiência, apresentando sensibilidade superior a 0,8 e especificidade superior a 0,89. O modelo foi capaz de estimar a probabilidade de correlação entre a imagem analisada e cada subtipo de amiloidose cardíaca. Os autores também destacaram o risco de sobreajuste (<italic>overfitting</italic>), especialmente em cenários com número reduzido de imagens para treinamento. Nesse caso, o algoritmo pode apresentar desempenho elevado nos dados utilizados para treinamento, mas falhar na generalização para conjuntos externos. Para mitigar esse risco, foram empregadas estratégias como aumento artificial do conjunto de dados (<italic>data augmentation</italic>) e validação cruzada, o que contribuiu para maior robustez do modelo.</p>
<p>No estudo de Miller et al.,<sup><xref ref-type="bibr" rid="B13">13</xref></sup> reconhece-se que a interpretação visual da SPECT constitui padrão na avaliação diagnóstica da amiloidose por ATTR, embora apresente caráter subjetivo. Os autores avaliaram abordagem de <italic>deep learning</italic> para quantificação volumétrica automatizada de tecnécio-99m (<sup>99m</sup>Tc)-pirofosfato, utilizando segmentação de estruturas anatômicas co-registradas em mapas de atenuação da tomografia computadorizada em pacientes com suspeita de amiloidose por ATTR. Os resultados demonstraram que a segmentação baseada em <italic>deep learning</italic> não foi influenciada pelo padrão de captação do radiotraçador e permitiu quantificação automática de imagens de captação focal, como as obtidas com <sup>99m</sup>Tc-pirofosfato. O modelo apresentou desempenho elevado (AUC = 0,989; IC 95%: 0,974-1,00), indicando potencial para identificação precisa de pacientes amiloidose por ATTR. Portanto, tal abordagem apresenta potencial de ser usada na identificação precisa de pacientes com amiloidose por ATTR.</p>
</sec>
<sec>
<title>Desempenho da inteligência artificial na avaliação da cintilografia com traçadores ósseos</title>
<p>No contexto do diagnóstico da amiloidose cardíaca por meio da aplicação de IA na análise de exames de imagem, é possível estruturar sistemas integrados aos prontuários eletrônicos, de forma semelhante ao modelo descrito por Huda et al.,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> porém direcionados à interpretação automatizada de imagens cintilográficas.</p>
<p>Delbarre et al.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> propuseram modelo de <italic>deep learning</italic> para análise automatizada de cintilografia com traçadores ósseos de corpo inteiro com <sup>99m</sup>Tc, fundamentado na premissa de que captação cardíaca significativa nesses exames é fortemente sugestiva de amiloidose por ATTR. O modelo apresentou sensibilidade de 98,9% e especificidade de 99,5% na validação cruzada. Na validação externa, observou-se discreta redução da sensibilidade para 96,1%, mantendo-se especificidade de 99,5%, com AUC de 0,999 em ambas as etapas.</p>
<p>Para o desenvolvimento do sistema, utilizou-se como variável preditora a captação cardíaca ≥ 2 segundo a escala de classificação de Perugini. O algoritmo foi treinado por meio de CNNs, utilizando rótulos em nível de imagem extraídos de exames registrados nos prontuários eletrônicos, permitindo a identificação automatizada de padrões sugestivos de amiloidose cardíaca. Assim como ressaltado por Castaño et al.,<sup><xref ref-type="bibr" rid="B9">9</xref></sup> a integração entre IA e sistemas de prontuário favorece rastreio eficiente de condições frequentemente sub-reconhecidas, como a associação entre captação cardíaca elevada na cintilografia com traçadores ósseos de corpo inteiro e amiloidose por ATTR, contribuindo para identificação em estágios mais precoces.</p>
<p>Embora a cintilografia com traçadores ósseos não substitua integralmente todos os métodos diagnósticos, Delbarre et al.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> destacaram que, quando ela é positiva e não há evidência de gamopatia monoclonal, o exame pode permitir diagnóstico não invasivo definitivo de cardiomiopatia por ATTR, especialmente em pacientes idosos ou fragilizados, nos quais a biópsia miocárdica apresenta maior risco.</p>
<p>Considerando que o diagnóstico de amiloidose cardíaca pode ser estabelecido de forma não invasiva por meio da cintilografia com traçadores ósseos e que a avaliação visual é inerentemente subjetiva, podendo resultar em interpretações equivocadas, Spielvogel et al.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> desenvolveram um sistema de IA para triagem padronizada e reprodutível da doença. O modelo foi treinado a partir de banco de dados multinacional de cintilografia com traçadores ósseos marcados com <sup>99m</sup>Tc, abrangendo diferentes traçadores e <italic>scanners</italic>. Na coorte austríaca, a validação cruzada demonstrou AUC de 1,00 (IC 95%: 1,00-1,00). Na validação externa, os resultados permaneceram elevados, com AUC de 0,997 (IC 95%: 0,993-0,999) no Reino Unido, 0,925 (IC 95%: 0,871-0,971) na China e 1,00 (IC 95%: 0,999-1,000) nas coortes italianas. Considerando que há cerca de uma década, a biopsia miocárdica representa a única modalidade para diagnosticar amiloidose cardíaca, a cintilografia com traçadores ósseos representa um marco no avanço do diagnóstico da amiloidose cardíaca, principalmente quando somada à IA. Até aproximadamente 1 década atrás, a biópsia miocárdica representava a única modalidade definitiva para o diagnóstico de amiloidose cardíaca. A consolidação da cintilografia com traçadores ósseos constituiu avanço significativo nesse cenário, sobretudo no diagnóstico da amiloidose por ATTR. A incorporação da IA a essa modalidade amplia ainda mais seu potencial, ao reduzir a subjetividade da interpretação e aumentar a padronização e a confiabilidade diagnóstica.</p>
<p>No referido estudo multicêntrico, a captação cardíaca intensa foi identificada de forma automatizada e consistente em todos os traçadores utilizados na investigação da amiloidose cardíaca. Adicionalmente, a triagem baseada em IA para detecção de captação sugestiva de amiloidose cardíaca em pacientes submetidos à cintilografia com traçadores ósseos de corpo inteiro configura ferramenta potencialmente valiosa para a identificação precoce da doença e para a otimização dos fluxos assistenciais. Nesse contexto, a implementação dessa estratégia pode favorecer o encaminhamento oportuno para avaliação especializada e possibilitar início mais precoce de terapias modificadoras da doença, com potencial impacto na redução da mortalidade.</p>
</sec>
<sec>
<title>Inteligência artificial na avaliação da ressonância magnética cardíaca</title>
<p>A RMC com realce tardio pelo gadolínio (RTG) constitui método fundamental na investigação da amiloidose cardíaca, dada a capacidade de demonstrar alterações morfológicas e padrões de realce característicos. Entretanto, sua utilização pode ser limitada em pacientes com insuficiência renal significativa, condição frequentemente associada à amiloidose, devido ao risco relacionado ao uso de contraste.</p>
<p>Ma et al.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> investigaram a viabilidade do diagnóstico por meio de RMC sem contraste, utilizando mapeamento de T1 nativo associado a análise radiômica automatizada baseada em IA. O modelo foi treinado para reconhecer padrões específicos de deposição amiloide e estimar, de forma indireta, o volume extracelular (VEC), parâmetro tradicionalmente calculado a partir de sequências pré e pós-contraste com gadolínio. Na abordagem proposta, o VEC foi estimado com precisão por meio da identificação automatizada das regiões de interesse miocárdicas. O modelo apresentou precisão de 86%, sensibilidade de 94%, especificidade de 85% e AUC de 0,915 no conjunto de teste. Diferentemente da cintilografia com traçadores ósseos, cuja principal aplicabilidade se concentra na identificação de amiloidose por ATTR, a RMC sem contraste demonstrou potencial para diagnóstico efetivo da amiloidose cardíaca, particularmente na amiloidose por AL.</p>
<p>Em consonância com tal perspectiva, Nowak et al.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> destacaram que o valor diagnóstico da RMC decorre de sua capacidade de integrar múltiplas sequências para avaliação detalhada da função miocárdica, edema, inflamação e fibrose. O VEC, nesse contexto, permite quantificação não invasiva da deposição amiloide miocárdica e pode influenciar decisões terapêuticas.</p>
<p>Considerando que a RMC é modalidade de referência para o diagnóstico de amiloidose cardíaca, Agibetov et al.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> observaram que seus achados podem ser inespecíficos, especialmente em centros com menor volume de casos. Para minimizar esse risco, desenvolveram algoritmo baseado em CNNs aplicado a uma coorte de 502 pacientes. Independentemente da técnica de <italic>deep learning</italic> empregada, os modelos treinados com imagens de RTG apresentaram melhor desempenho. O ajuste fino (<italic>fine-tuning</italic>) do modelo resultou em AUC de 0,96, sensibilidade de 94% e especificidade de 90%. A classificação automatizada apresentou desempenho semelhante ao de especialistas humanos. Contudo, por se tratar de estudo unicêntrico, a generalização dos resultados requer cautela.</p>
<p>Martini et al.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> também utilizaram <italic>deep learning</italic> para análise automatizada de imagens de RMC e estimativa da probabilidade de amiloidose cardíaca. Entre os achados mais específicos, destacaram o padrão de pseudo-hipertrofia biventricular associado a RTG transmural difuso. A análise automatizada de sequências de RTG nas projeções 2C, 4C e eixo curto mostrou-se mais rápida e apresentou acurácia semelhante à avaliação especializada, com AUC de 0,982, valor preditivo positivo de 83%, <italic>recall</italic> de 95% e <italic>F1-score</italic> de 89%.</p>
</sec>
<sec>
<title>Desempenho da inteligência artificial na avaliação de testes genéticos e biópsias</title>
<p>Outro campo promissor na aplicação da IA ao diagnóstico da amiloidose cardíaca, especialmente na forma por AL, envolve a sistematização da análise de testes genéticos voltados à identificação de mutações somáticas em cadeias leves de imunoglobulinas. Garofalo et al.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> demonstraram, por meio de modelo de aprendizado de máquina, associação entre mutações somáticas adquiridas durante a maturação dos linfócitos B e o desenvolvimento de amiloidose cardíaca. Essas mutações afetam a estabilidade estrutural das cadeias leves, favorecendo o dobramento incorreto da proteína e a consequente formação de depósitos amiloides. O modelo apresentado obteve sensibilidade de 76%, especificidade de 82% e AUC de 0,87, evidenciando capacidade preditiva relevante na identificação de sequências consideradas tóxicas. Além disso, os autores destacaram que a reversão dessas mutações pode abolir o fenótipo tóxico, reforçando a importância da caracterização molecular detalhada.</p>
<p>Considerando a diversidade das sequências patogênicas envolvidas, o uso de IA configura estratégia apropriada para organizar e analisar grande volume de variáveis genéticas, atuando como preditor de toxicidade. Dessa forma, o algoritmo pode identificar perfis moleculares associados a maior risco de desenvolvimento de amiloidose cardíaca, contribuindo assim para estratificação de risco e potencial diagnóstico precoce.</p>
<p>No âmbito da histopatologia, a biópsia permanece como evidência diagnóstica definitiva na cardiomiopatia amiloide, apesar de seu caráter invasivo. Nesse contexto, a integração entre técnicas histológicas e <italic>deep learning</italic> também tem se mostrado promissora. Yang et al.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> propuseram abordagem baseada em rede neural capaz de transformar imagens de autofluorescência em imagens equivalentes às obtidas por microscopia de campo claro e luz polarizada, simulando o efeito da coloração pelo vermelho Congo.</p>
<p>Atualmente, o padrão-ouro diagnóstico baseia-se na identificação de birrefringência sob luz polarizada cruzada após coloração com vermelho Congo. Entretanto, esse processo é influenciado por variabilidade técnica na coloração, qualidade do preparo das lâminas e disponibilidade de equipamentos adequados, além de envolver custos elevados. O modelo proposto por Yang et al.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> demonstrou que as imagens geradas digitalmente apresentaram qualidade comparável às lâminas coradas convencionalmente, com potencial redução de custos, menor dependência técnica e melhor armazenamento digital das amostras, considerando que <italic>scanners</italic> especializados para captura de birrefringência nem sempre estão disponíveis.</p>
<p>Assim, embora haja crescente interesse em métodos diagnósticos não invasivos para amiloidose cardíaca, os avanços na aplicação da IA à análise genética e histopatológica também representam contribuição relevante, o que melhora a precisão diagnóstica e a padronização dos processos laboratoriais.</p>
</sec>
<sec>
<title>Barreiras de implementação da inteligência artificial no fluxo de trabalho da medicina</title>
<p>A implementação da IA na prática médica apresenta potencial significativo para ampliar a precisão diagnóstica, otimizar processos assistenciais, reduzir custos e apoiar a tomada de decisão clínica. Contudo, sua incorporação ao fluxo de trabalho enfrenta desafios multifatoriais que podem ser agrupados em dimensões técnicas, éticas, organizacionais e humanas.</p>
<p>Do ponto de vista técnico, os modelos de IA dependem de bases de dados estruturadas, completas e padronizadas. Entretanto, muitos sistemas de saúde ainda operam com registros fragmentados, inconsistentes ou incompletos, o que compromete o treinamento adequado e a capacidade de generalização dos algoritmos. Além disso, dados historicamente enviesados podem perpetuar desigualdades assistenciais, resultando em recomendações inadequadas para determinados grupos populacionais. A interoperabilidade entre diferentes sistemas de informação também constitui desafio relevante, dificultando a integração fluida da IA aos ambientes clínicos já estabelecidos.</p>
<p>Sob a perspectiva ética e legal, emergem questionamentos quanto à responsabilização em caso de erro clínico envolvendo recomendações algorítmicas. A definição de responsabilidade entre desenvolvedores, instituições e profissionais permanece complexa. Soma-se a isso a preocupação com privacidade, segurança e governança de dados, especialmente quando há compartilhamento interinstitucional para treinamento ou validação de modelos.</p>
<p>No âmbito organizacional, a adoção de ferramentas baseadas em IA exige integração eficiente aos fluxos assistenciais. Soluções que adicionam etapas ao processo ou interrompem rotinas consolidadas tendem a gerar resistência e sobrecarga operacional. Além disso, é imprescindível que médicos, enfermeiros e demais profissionais sejam capacitados para interpretar criticamente as recomendações fornecidas pelos sistemas, utilizando-as como suporte e não como substituição do julgamento clínico. A implementação também demanda investimentos em infraestrutura tecnológica, manutenção e atualização contínua dos modelos, o que pode representar barreira financeira para determinadas instituições.</p>
<p>Por fim, a dimensão humana envolve aspectos relacionados à aceitação profissional e à confiança do paciente. Parte dos profissionais pode manifestar desconfiança quanto à tecnologia ou perceber a IA como ameaça ao seu papel clínico. A chamada &quot;caixa-preta&quot; dos algoritmos, em que o processo decisório não é plenamente transparente, pode reduzir a confiança na ferramenta e dificultar sua incorporação à prática clínica. Do ponto de vista do paciente, a confiança em decisões influenciadas por algoritmos ainda não é universal. Em contrapartida, há risco de dependência excessiva da IA por parte dos profissionais, o que pode comprometer o exercício do raciocínio clínico independente caso não haja postura crítica e reflexiva.</p>
</sec>
</sec>
<sec sec-type="conclusions">
<title>Conclusão</title>
<p>Com base nos achados desta revisão, a IA configura-se como ferramenta promissora na otimização do rastreio e do diagnóstico da amiloidose cardíaca. Sua aplicação em diferentes modalidades diagnósticas demonstra potencial para acelerar a identificação da doença, contribuir para maior precisão diagnóstica e, consequentemente, favorecer melhores desfechos clínicos.</p>
<p>A elevada capacidade de processamento e análise de grandes volumes de dados permite à IA reconhecer padrões complexos, ampliar sua capacidade de generalização, desde que treinada com bases robustas e representativas, e auxiliar na detecção precoce da amiloidose cardíaca. Ademais, a utilização de modelos automatizados pode reduzir a subjetividade da interpretação humana, minimizar a necessidade de procedimentos invasivos em determinados contextos e racionalizar o uso de recursos em saúde.</p>
<p>Entretanto, apesar dos avanços observados, a consolidação da IA na prática clínica exige aprimoramento contínuo dos modelos, validação externa em populações diversas e integração eficiente aos fluxos assistenciais. São igualmente fundamentais o planejamento estratégico da implementação, a capacitação dos profissionais de saúde, a governança ética no manejo de dados e o monitoramento permanente do desempenho algorítmico.</p>
</sec>
</body>
<back>
<fn-group>
<fn fn-type="financial-disclosure" id="fn5"><label>Fontes de Financiamento</label>
<p>O presente estudo não teve fontes de financiamento externas.</p></fn>
<fn fn-type="other" id="fn6"><label>Vinculação Acadêmica</label>
<p>Não há vinculação deste estudo a programas de pós-graduação.</p></fn>
<fn fn-type="other" id="fn7"><label>Aprovação Ética e Consentimento Informado</label>
<p>Este artigo não contém estudos com humanos ou animais realizados por nenhum dos autores.</p></fn>
<fn fn-type="other" id="fn8"><label>Uso de Inteligência Artificial</label>
<p>Os autores não utilizaram ferramentas de inteligência artificial no desenvolvimento deste trabalho.</p></fn>
</fn-group>
<sec sec-type="data-availability" specific-use="data-in-article">
<title>Disponibilidade de Dados</title>
<p>Os conteúdos subjacentes ao texto da pesquisa estão contidos no manuscrito.</p>
</sec>
</back>
</sub-article>
</article>
