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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.20260054i</article-id>
<article-id pub-id-type="other">abcimg.20260054i</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Recognition of Clinical Stages and Myocardial Damage in Aortic Stenosis: Beyond Diagnosis – To Op or Not To Op</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0009-0000-6530-1400</contrib-id>
<name><surname>Vasconcelos</surname><given-names>Daniel Franca</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>acquisition of data</role>
<role>analwysis and interpretation of the data</role>
<role>writing of the manuscript</role>
<role>critical revision of the manuscript for intellectual content</role>
</contrib>
<aff id="aff1">
<label>1</label>
<institution content-type="orgname">Universidade de Brasília</institution>
<institution content-type="orgdiv1">Hospital Universitário de Brasília</institution>
<institution content-type="orgdiv2">Faculdade de Medicina</institution>
<addr-line>
<named-content content-type="city">Brasília</named-content>
<named-content content-type="state">DF</named-content>
</addr-line>
<country country="BR">Brazil</country>
<institution content-type="original">Universidade de Brasília, Faculdade de Medicina, Hospital Universitário de Brasília, Brasília, DF – Brazil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c1"><label>Mailing Address:</label> <bold>Daniel Franca Vasconcelos</bold> • Universidade de Brasília. Hospital Universitário de Brasília. Postal code: <postal-code>70910-900</postal-code>. Brasília, DF – Brazil E-mail: <email>dfrancav@uol.com.br</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 responsible for the review:</label><p>Marcelo Tavares</p></fn>
</author-notes>
<pub-date publication-format="electronic" date-type="pub">
<day>29</day>
<month>06</month>
<year>2026</year></pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2026</year></pub-date>
<volume>39</volume>
<issue>2</issue>
<elocation-id>e20260054</elocation-id>
<history>
<date date-type="received">
<day>07</day>
<month>04</month>
<year>2026</year>
</date>
<date date-type="rev-recd">
<day>22</day>
<month>04</month>
<year>2026</year>
</date>
<date date-type="accepted">
<day>22</day>
<month>04</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>
<p>Severe aortic stenosis is a progressive clinical entity that has historically developed alongside descriptions of pathological anatomy, cardiovascular semiology, heart surgery, and percutaneous cardiovascular interventions. Indication for valve replacement in patients with severe aortic stenosis is still based on symptom onset. With advances in surgical techniques, especially transcatheter implantation, the focus has shifted to identifying early markers of myocardial damage that may indicate irreversible myocardial injury. This review article seeks to provide a comprehensive analysis of methods for identifying myocardial damage in patients with severe aortic stenosis, including clinical evaluation, electrocardiography (ECG), echocardiography, cardiac magnetic resonance imaging (CMR), and plasma biomarkers. It also discusses the staging of myocardial damage and the optimal timing for therapeutic intervention based on clinical, functional, and structural findings. Recent studies designed to address how to manage asymptomatic patients with aortic stenosis have yielded divergent results. Accordingly, the aim is to assist clinicians in deciding the optimal timing for valve replacement, taking individual patient characteristics into account.</p>
</abstract>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>Aortic Valve Stenosis</kwd>
<kwd>Echocardiography</kwd>
<kwd>Magnetic Resonance Imaging</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="6"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="43"/>
</counts>
</article-meta>
</front>
<body>
<fig id="f1">
<graphic xlink:href="2675-312X-abcic-39-02-e20260054-gf01.tif"/>
<p>Proposed flowchart for guiding the management of patients with severe aortic stenosis, differentiating between healthy and frail patients. AoS: aortic stenosis; TAVI: transcatheter aortic valve implantation.</p>
</fig>
<sec sec-type="intro">
<title>Introduction</title>
<p>Aortic stenosis is the most frequently surgically treated valvular heart disease in the current population.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> The clinical entity has evolved concomitantly with descriptions of pathological anatomy, cardiovascular semiology, cardiac surgery, and, recently, percutaneous cardiovascular interventions.</p>
<p>In 1663, the French physician Lazare Rivière described the first anatomopathological finding of a stenotic aortic valve.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Subsequently, Giovanni Battista Morgagni and Jean-Nicolas Corvisar described an &quot;ossified aortic valve&quot; that did not allow the passage of relevant-sized structures. In 1819, Laënnec described ossified aortic stenosis as a valvular clinical entity with the currently recognized semiological characteristics.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
<p>The twentieth century was characterized by detailed anatomopathological description, knowledge of the pathophysiology of the disease, and the development of surgical techniques with increasingly sophisticated prostheses, followed by the development of percutaneous interventions in the twenty-first century. It is currently possible to estimate the degree of progression of aortic stenosis based on echocardiographic epidemiological studies.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
<p>Notwithstanding advances in knowledge of pathophysiology, the only current therapeutic option for calcified aortic valve stenosis remains valve replacement.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Current guidelines, including the Brazilian guideline, recommend that valve replacement be indicated in patients with severe aortic valve stenosis (peak Doppler velocity &gt; 4.0 m/s, mean gradient &gt; 40 mmHg, valve area &lt; 1.0 cm<sup>2</sup>, or indexed valve area &lt; 0.6 cm<sup>2</sup>/m<sup>2</sup>) who present with symptoms, or in patients with severe stenosis and reduced ejection fraction (&lt; 50%).<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
<p>With the advent of transcatheter aortic valve implantation (TAVI), it has become possible to perform valve replacement in frail patients with high surgical risk, for whom surgical intervention would be prohibitive.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> The enthusiasm stemming from the favorable results of percutaneous intervention and the development of new techniques for assessing myocardial damage has led to greater interest in identifying early markers of myocardial damage to indicate valve replacement.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
<p>The central question that therefore follows is: Since percutaneous intervention has proven to be safe, why not indicate valve replacement in patients with severe calcified stenosis before symptoms appear? Although the procedure is considered safe, it is not without risks. In some situations, it can worsen the clinical condition and quality of life, in addition to the fact that prosthesis durability has not been fully defined from an epidemiological point of view.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> The mortality of asymptomatic patients under expectant management is less than 1% per year, much lower than that expected after surgical valve replacement. On the other hand, the durability of the new prostheses (valve prostheses) has not been tested.</p>
<p>Regarding expectant management, several studies have attempted to identify myocardial damage through electrocardiography (ECG), exercise stress testing, reduction in ejection fraction and myocardial strain by echocardiography, transvalvular gradient response to physical stress echocardiography, myocardial fibrosis and edema by cardiac magnetic resonance imaging (CMR), and plasma biomarkers such as B‐type natriuretic peptide (BNP) and N-terminal pro‐B‐type natriuretic peptide (NT-proBNP).<sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
<p>In spite of all these advances, studies comparing expectant management with early intervention have not demonstrated benefits, and there are still challenges in defining the optimal timing for intervention.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> The purpose of this article is to review the methods for identifying myocardial damage and suggest the most appropriate timing for valve replacement intervention, before irreversible myocardial damage occurs, as well as to propose designs for future studies.</p>
<sec>
<title>Epidemiological implications</title>
<p>Calcified aortic valve stenosis has a prevalence of 0.4% in the general population, increasing to 1.7% at age 65 and 3.4% at age 75; in other words, it increases significantly after 65 years of age.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> Bicuspid aortic valve has a prevalence of 0.5% to 1.0% in the population and is responsible for approximately 50% of valve interventions, especially in younger patients.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> Surgery for calcified aortic valve stenosis represents 47% of all valve surgeries performed.<sup><xref ref-type="bibr" rid="B12">12</xref></sup></p>
<p>In spite of recent knowledge about the pathophysiology of calcified valve disease, to date there is no specific clinical treatment for this condition.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Symptom onset represents the defined threshold for the indication of valve replacement. From symptom onset, expectant management (without intervention) is associated with a 50% mortality rate within 2 years.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
</sec>
<sec>
<title>Pathophysiology</title>
<p>Calcified aortic valve disease shares the same pathophysiological mechanisms and risk factors as atherosclerotic disease. In the initial phase, the inflammatory process predominates, followed by the calcification phase.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> More recently, the deposition of lipoproteins, such as apoA1, apoB, apoE and lipoprotein(a), has been highlighted, followed by inflammation, oxidative stress, osteogenic differentiation of interstitial cells, and subsequent calcification.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
<p>Risk factors for the development of calcified valvular disease include bicuspid aortic valve, age, male sex, smoking, systemic arterial hypertension, dyslipidemia, obesity, metabolic syndrome, diabetes mellitus, elevated lipoprotein(a), mediastinal radiotherapy, chemotherapy, and rheumatological diseases.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B16">16</xref></sup> Regarding the risk of more rapid progression to severe aortic stenosis, the following stand out: advanced age, female sex, hemodynamic severity of the initial stenosis, degree of valve calcification, active smoking, uncontrolled systemic arterial hypertension, metabolic syndrome, hyperparathyroidism, chronic renal failure, and elevated lipoprotein(a).<sup><xref ref-type="bibr" rid="B16">16</xref></sup></p>
<p>The advent of percutaneous intervention in patients with prohibitive surgical risk has opened a window of therapeutic opportunity for these patients. On the other hand, a trend has emerged to perform this type of procedure in situations where the cost-benefit should be carefully discussed in the context of a multidisciplinary Heart Team. The concept of an extended Heart Team includes the participation of nephrologists, geriatricians, neurologists, nutritionists, patients, and family members, especially for the population of frail patients with multiple morbidities.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> Despite the lower risk compared to conventional surgery, studies in patients with high frailty have shown results that question the indiscriminate indication of early intervention.<sup><xref ref-type="bibr" rid="B18">18</xref></sup></p>
</sec>
<sec>
<title>Adaptation to pressure overload and myocardial damage</title>
<p>Following sustained pressure overload, an increase in myofibrillar content is observed, with a consequent increase in left ventricular mass. This increase in mass leads to a reduction in coronary microcirculation density and an increase in coronary vascular resistance. Coronary reserve is progressively reduced, initially only during exertion, and subsequently at rest as well.<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
<p>Consequently, the myocardium is subjected to repeated ischemia, initially manifesting as diastolic dysfunction.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> With recurrent ischemia, fibrosis subsequently develops. Initially, this fibrosis is interstitial, diffuse, and reversible after valve replacement. In later stages, the fibrosis is substitutive, focal, and irreversible. Subsequently, changes in the functional geometry of the left ventricle occur, resulting in increased end-diastolic pressure. This increase is transmitted to pulmonary venous pressure, and symptoms of pulmonary congestion appear (dyspnea on exertion).<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Ischemia may manifest with symptoms of angina. Impaired ejection flow, especially during exertion, is responsible for symptoms of pre-syncope and syncope, particularly during exertion.<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
<p>Once the mechanism of myocardial damage has been understood, it is imperative to use the available diagnostic tools in a rational and individualized manner. As previously mentioned, there is still no drug treatment for calcified aortic stenosis. Despite knowledge about the mechanisms of myocardial damage, we still do not fully understand the implications of early intervention before the onset of symptoms.<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
</sec>
<sec>
<title>Identifying myocardial damage</title>
<sec>
<title>Clinical evaluation</title>
<p>According to current guidelines, intervention in patients with severe aortic stenosis should be indicated when symptoms appear.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Although the classic symptoms (dyspnea, angina, and syncope) have been well defined, their identification can be challenging in certain populations.</p>
<p>Patients with aortic stenosis secondary to bicuspid aortic valve are typically younger (approximately 20 years younger than those with degenerative aortic stenosis), physically active, and without significant comorbidities.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> In these cases, in addition to clinical history and physical examination with the goal of identifying symptoms, an exercise stress test is recommended in order to identify functional limitations and reproducible symptoms.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
<p>In contrast, patients with degenerative calcified aortic stenosis present a completely different clinical profile. They are elderly, often with orthopedic problems, chronic lung diseases, and cognitive impairment. In this scenario, it is very difficult to adequately identify symptoms of ischemia or congestion.<sup><xref ref-type="bibr" rid="B21">21</xref></sup></p>
<p>Regardless of profile, asymptomatic patients with severe aortic stenosis should be monitored periodically every 3 to 6 months, with the expectation of identifying emerging symptoms or changes on ECG and echocardiography.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
</sec>
<sec>
<title>Electrocardiogram</title>
<p>ECG can provide important information related to left ventricular overload in the assessment of myocardial damage. An ECG with findings suggestive of left ventricular overload (left ventricular hypertrophy) in asymptomatic patients with severe aortic stenosis, estimated by the transvalvular gradient on echocardiography, represents a warning sign (yellow flag) that justifies intensified monitoring.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> Studies of prognostic markers suggest that ventricular hypertrophy, identified by ECG, echocardiogram, or CMR, represents a worse outcome compared to patients without ventricular hypertrophy. The presence of arrhythmia, especially atrial fibrillation, can result from increased ventricular filling pressure secondary to diastolic dysfunction, followed by left atrial overload, and may indicate myocardial damage.</p>
</sec>
<sec>
<title>Exercise stress test</title>
<p>Exercise stress tests play an important role in the evaluation of asymptomatic patients with severe aortic stenosis. This test can reveal typical symptoms (dyspnea disproportionate to exertion, precordial angina, or syncope) that were not detected at rest, in up to 30% of individuals considered asymptomatic, thus guiding the decision to intervene. In addition to symptoms, a hypotensive response to exertion, ischemia on ECG, or the appearance of malignant arrhythmias are also indicators of greater severity, with a relative risk more than 7 times higher compared to patients with normal results.<sup><xref ref-type="bibr" rid="B23">23</xref></sup></p>
</sec>
<sec>
<title>Echocardiography</title>
<p>Transthoracic echocardiography is the method of choice for evaluating aortic valve anatomy, quantifying stenosis severity, identifying associated valvular and diastolic dysfunction, estimating left ventricular filling pressures (E/e′ ratio), estimating left ventricular ejection fraction, assessing right ventricular function, and estimating pulmonary arterial pressure.<sup><xref ref-type="bibr" rid="B24">24</xref></sup> Although the traditional cutoff point for systolic dysfunction is an ejection fraction of 50%, values above this threshold, but with significant progressive decline (&gt; 10%), may represent relevant myocardial damage and justify valve replacement, in a manner similar to patients with cancer undergoing chemotherapy.<sup><xref ref-type="bibr" rid="B25">25</xref></sup></p>
<p>Very severe aortic stenosis (Vmax &gt; 5 m/s) or progression of stenosis severity (&gt; 0.3 m/s/year) is associated with onset of symptoms and worsening mortality in the first year.<sup><xref ref-type="bibr" rid="B24">24</xref></sup> The European guideline considers this condition a class IIa indication for intervention.</p>
<p>Serial evaluation with progressive reduction of ventricular function is particularly informative. For example, a patient with an initial ejection fraction of 68% who shows a progressive reduction to 60% demonstrates a decline greater than 10%, which may signify significant myocardial damage in progression.<sup><xref ref-type="bibr" rid="B25">25</xref></sup></p>
<p>Valvulo-arterial impedance (Zva) represents a marker of myocardial damage, calculated as systolic blood pressure (SBP) plus mean transvalvular gradient (MG) divided by the stroke volume indexed by body surface area (SVI), as follows: Zva = (SBP + MG) / SVI. Values greater than 4.5 have prognostic importance for indicating valve replacement.<sup><xref ref-type="bibr" rid="B26">26</xref></sup></p>
<p>The left atrium undergoes enlargement proportionally to diastolic dysfunction, representing the chronic progression of atrial overload. Left atrial enlargement and elevated pulmonary artery systolic pressure represent signs of myocardial damage, as do right ventricular dysfunction and tricuspid regurgitation.<sup><xref ref-type="bibr" rid="B27">27</xref></sup></p>
<p>Genereux et al. analyzed patients from the PARTNER 2 study, who were grouped and classified according to the presence or absence of cardiac damage detected by echocardiography before aortic valve replacement in the following manner: no extravalvular cardiac damage (stage 0), left ventricular damage (stage 1), left atrial or mitral valve damage (stage 2), pulmonary vasculature or tricuspid valve damage (stage 3), or right ventricular damage (stage 4). Among the 1,661 patients with echocardiographic data, 1-year mortality was 4.4% in stage 0, 9.2% in stage 1, 14.4% in stage 2, 21.3% in stage 3, and 24.5% in stage 4 (p for trend &lt; 0.0001). The extent of cardiac damage was independently associated with higher mortality after aortic valve replacement (hazard ratio 1.46 for each stage increment, 95% confidence interval 1.27–1.67, p &lt; 0.0001). These results suggest that stages other than 0 and 1 demonstrate structural and functional changes in which symptoms were likely already present and which had prognostic importance. In this case as well, the sum of myocardial damage markers suggests that valve replacement before the onset of symptoms may be an acceptable approach, even though the results have been controversial to date.<sup><xref ref-type="bibr" rid="B28">28</xref></sup></p>
</sec>
<sec>
<title>Global longitudinal strain</title>
<p>Echocardiographic assessment may also include global longitudinal myocardial strain, which has been shown to be a more sensitive tool for identifying early systolic dysfunction.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Although the traditional cutoff points for strain in patients with ventricular dysfunction and patients with aortic stenosis are −17% and −14%, respectively, progressive strain reduction can also be interpreted as evidence of progressive myocardial damage.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup> Studies have correlated reduced myocardial strain with the onset of symptoms. Reduced strain also has prognostic value after valve replacement.<sup><xref ref-type="bibr" rid="B29">29</xref></sup></p>
<p>Atrial strain is an additional tool that can be used when equipment with this feature is available. Although the data are controversial, atrial strain can identify atrial dysfunction before remodeling and predict the onset of atrial fibrillation during the course of the disease and post-operatively<sup><xref ref-type="bibr" rid="B30">30</xref></sup> (<xref ref-type="fig" rid="f2">Figure 1</xref>).</p>
<fig id="f2">
<label>Figure 1</label>
<caption><title>Two-dimensional transthoracic echocardiography with color Doppler demonstrating severe aortic stenosis. Top right: Parasternal longitudinal view showing left ventricular hypertrophy and calcified aortic valve. Bottom right: Transvalvular velocity &gt; 4.5 m/s and mean gradient = 50 mmHg. Left: Bull&apos;s eye map showing normal global longitudinal strain = 21.1%.</title></caption>
<graphic xlink:href="2675-312X-abcic-39-02-e20260054-gf02.tif"/>
</fig>
</sec>
<sec>
<title>Stress echocardiography</title>
<p>Although current guidelines do not recommend stress echocardiography as a tool for stratifying asymptomatic patients with severe aortic stenosis,<sup><xref ref-type="bibr" rid="B5">5</xref></sup> its use during physical or pharmacological stress (dobutamine) to assess the transvalvular gradient, electrocardiographic tracing, and ventricular functional response continues to be investigated.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Studies comparing patients with positive versus negative stress tests, subsequently undergoing valve intervention, show variability in results, without significant and consistent differences in long-term prognosis between groups.<sup><xref ref-type="bibr" rid="B31">31</xref></sup> Further studies are needed to define the role of stress echocardiography in the management of asymptomatic patients with severe aortic stenosis.</p>
</sec>
</sec>
<sec>
<title>Cardiac magnetic resonance imaging</title>
<p>CMR has emerged as an important non-invasive marker of myocardial damage in severe aortic stenosis.<sup><xref ref-type="bibr" rid="B32">32</xref></sup> In addition to assessing the severity of stenosis with results comparable to echocardiography, it is now possible, by means of native T1 mapping, to identify and quantify diffuse interstitial myocardial fibrosis lesions that may be partially reversible after valve replacement. Late gadolinium enhancement allows identification of focal fibrosis, which is usually irreversible, and it is an important indicator for early valve replacement.<sup><xref ref-type="bibr" rid="B32">32</xref>,<xref ref-type="bibr" rid="B33">33</xref></sup></p>
<p>Some initial studies have suggested that anticipating valve replacement in patients with fibrotic changes detected by CMR could favorably modify the clinical and functional outcomes.<sup><xref ref-type="bibr" rid="B34">34</xref></sup> However, the recently published randomized EVOLVED study with 224 patients did not demonstrate benefits in anticipating valve replacement before the onset of symptoms, even in the presence of myocardial fibrosis detected by CMR.<sup><xref ref-type="bibr" rid="B35">35</xref></sup> Likewise, Myhr et al., comparing 42 symptomatic patients with 80 asymptomatic patients, showed that the presence of myocardial fibrosis identified by CMR with late enhancement did not demonstrate significant differences in relation to progression after valve replacement<sup><xref ref-type="bibr" rid="B36">36</xref></sup> (<xref ref-type="fig" rid="f3">Figure 2</xref>; <xref ref-type="other" rid="f4">Video 1</xref>).</p>
<fig id="f3">
<label>Figure 2</label>
<caption><title>Cardiac magnetic resonance imaging in a patient with severe aortic stenosis. Late gadolinium enhancement demonstrates a pattern of focal subendocardial fibrosis. These changes represent evidence of irreversible structural myocardial damage (image kindly provided by Dr. Luiz Augusto Quaglia).</title></caption>
<graphic xlink:href="2675-312X-abcic-39-02-e20260054-gf03.tif"/>
</fig>
<media id="f4" mime-subtype="mp4" mimetype="video" xlink:href="2675-312X-abcic-39-02-e20260054-m01.mp4">
<label>Video 1</label>
<caption><title>Cardiac magnetic resonance imaging demonstrating severe aortic stenosis with myocardial structural remodeling and focal fibrosis. Courtesy of Dr. Luiz Augusto Quaglia. In: <ext-link ext-link-type="uri" xlink:href="http://abcimaging.org/supplementary-material/2026/3902/ABCImag-2026-0054_AR_Video_1.mp4">http://abcimaging.org/supplementary-material/2026/3902/ABCImag-2026-0054_AR_Video_1.mp4</ext-link></title></caption>
</media>
<p>On the other hand, another recently published randomized study by Généreux et al. (EARLY TAVR), albeit with some methodological limitations, evaluated a significantly larger sample (901 patients), suggesting favorable results for early percutaneous intervention in asymptomatic patients with severe aortic stenosis.<sup><xref ref-type="bibr" rid="B36">36</xref></sup> Although their conclusions were favorable, mortality and prognosis were similar. The intervention reduced the outcome of hospitalization. A large part of these hospitalizations resulted from decompensation in the clinical follow-up group, in patients who underwent intervention in the subsequent 90 days. Similar results were found in the AVATAR study (Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis).<sup><xref ref-type="bibr" rid="B37">37</xref></sup></p>
</sec>
<sec>
<title>Plasma biomarkers</title>
<p>Elevated BNP and NT-proBNP levels are correlated with increased ventricular filling pressure and predict worse prognosis in severe aortic stenosis.<sup><xref ref-type="bibr" rid="B38">38</xref></sup> Elevated values may reflect myocardial damage with consequent diastolic dysfunction.<sup><xref ref-type="bibr" rid="B38">38</xref></sup> Similarly to other markers of myocardial damage, perhaps progressive worsening in serial evaluations, when associated with other markers, may indicate the need for early valve replacement.</p>
<p>Other biochemical markers have also shown prognostic value in surgical outcome during preoperative evaluation. High-sensitivity troponin T has important prognostic value. Elevations in troponin T, even slight ones, in patients with severe aortic stenosis correlate with worse clinical progression and a higher risk of adverse events.<sup><xref ref-type="bibr" rid="B39">39</xref></sup> This marker can identify structural cellular damage that is already present in the myocardium.<sup><xref ref-type="bibr" rid="B39">39</xref></sup> Osteopontin, a glycoprotein secreted by cells linked to inflammatory and remodeling processes, has been shown to be a marker of irreversible myocardial damage. Studies have shown that osteopontin predicts adverse clinical outcomes in patients after treatment of severe aortic stenosis with TAVI.<sup><xref ref-type="bibr" rid="B40">40</xref></sup> Annexin A1, studied in pericardial fluid of patients with severe aortic stenosis, has been shown to be a marker of atrial fibrillation associated with aortic stenosis, representing a marker of atrial remodeling.<sup><xref ref-type="bibr" rid="B41">41</xref></sup> Plasma ACE2 activity has also been shown to be associated with severe myocardial fibrosis and to predict mortality in patients with aortic stenosis.<sup><xref ref-type="bibr" rid="B42">42</xref></sup> Elevated levels indicate pathological myocardial remodeling processes with the development of fibrosis.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
<p>Although biomarkers can identify patients with worse prognosis, current guidelines still do not mention their role in decision-making.</p>
</sec>
</sec>
<sec sec-type="discussion">
<title>Discussion: When to intervene?</title>
<p>In spite of the multiple diagnostic tools available and the numerous published studies, the optimal timing to perform aortic valve replacement (to op) remains controversial and without absolute consensus (not to op).<sup><xref ref-type="bibr" rid="B7">7</xref></sup> In the real world, we have observed increasingly frequent indications for TAVI placement in patients under 65 years of age. Despite the safety of the procedure, long-term results have shown that mortality is higher in the percutaneous intervention group. The <xref ref-type="fig" rid="f1">Central Illustration</xref> presents a proposed flowchart to guide the follow-up of asymptomatic patients with severe aortic stenosis.</p>
<p>Clinical experience suggests prudence and common sense in decision-making. In young, healthy, and asymptomatic patients with severe calcified aortic valve stenosis, close follow-up is recommended with consultations every 3 to 6 months, including:</p>
<list list-type="bullet">
<list-item><p>Serial ECG</p></list-item>
<list-item><p>Echocardiogram with evaluation of ejection fraction and myocardial strain</p></list-item>
<list-item><p>Exercise stress test (if appropriate for the patient&apos;s clinical profile)</p></list-item>
<list-item><p>Plasma biomarkers (BNP/NT-proBNP, high-sensitivity troponin T)</p></list-item>
<list-item><p>CMR with T1 and T2 maps and late gadolinium enhancement (less frequently, in selected situations)</p></list-item>
</list>
<p>Progressive changes with worsening ventricular function, whether due to ejection fraction or myocardial strain, left atrial enlargement, stenosis progression, and signs of elevated pulmonary arterial pressure, coupled with an abnormal exercise stress test (whether due to ischemia, decreased pressure, or malignant arrhythmias), may represent grounds for recommending valve replacement.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
<p>In elderly patients with frailty that poses difficulties in adequately assessing symptoms, in addition to the parameters listed above (with the exception of exercise stress test, which may be contraindicated), assessment should integrate the multidimensional concept of frailty (extended Heart Team) to assist in the decision between performing elective valve intervention or clinical management with rigorous follow-up.<sup><xref ref-type="bibr" rid="B43">43</xref></sup></p>
<p>For all patients, the classification of myocardial damage proposed by Genereux et al., after evaluating the population of the PARTNER study, can assist in identifying the initial stages of myocardial damage and justify the surgical indication described above. When applying the classification, it is important to bear in mind that all stages, except stage 0, are associated with a worse prognosis, justifying further monitoring and anticipation of intervention when appropriate.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
</sec>
<sec sec-type="conclusions">
<title>Conclusion</title>
<p>Severe aortic stenosis poses a challenge in current clinical management, characterized by the technical possibility of safe percutaneous intervention, but without absolute clarity regarding the optimal timing. Advances in the pathophysiological understanding of the disease and the development of sophisticated diagnostic tools (strain echocardiography, CMR with tissue mapping, and specific biomarkers) allow for the identification of myocardial damage in progressive stages before the onset of symptoms. Although the pathophysiological rationale points to intervention based on the identification of myocardial damage markers, studies conducted to date have yielded controversial results. Characteristics of the disease&apos;s phenotypic expression, which influence ventricular remodeling, worsening diastolic and systolic function, atrial remodeling, and the reaction of the pulmonary microcirculation, can affect the timing of symptom onset. Well-designed studies with consistent results are needed to incorporate the intervention approach into the guidelines.</p>
<p>An individualized and risk-stratified approach is recommended, considering the patient&apos;s clinical profile (young versus elderly, frail versus healthy), the presence and progression of markers of structural and functional myocardial damage, associated comorbidities, and the patient&apos;s informed preferences. The decision regarding closer follow-up intervals versus elective intervention should be based on multidisciplinary discussion within the context of an extended Heart Team. In the elderly population, whether asymptomatic or symptomatic, in the presence of a phenotype of left ventricular hypertrophy, the possibility of amyloid disease should always be considered.</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>
<ack>
<title>Acknowledgements</title>
<p>The author would like to thank the echocardiography and CMR teams who contributed to compilation of the clinical images presented in this manuscript.</p>
</ack>
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<sub-article article-type="translation" id="S1" xml:lang="pt">
<front-stub>
<article-id pub-id-type="doi">10.36660/abcimg.20260054</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Artigo de Revisão</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Reconhecimento dos Estágios Clínicos e do Dano Miocárdico na Estenose Aórtica: Muito Além do Diagnóstico – <italic>To Op or Not To Op</italic></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0009-0000-6530-1400</contrib-id>
<name><surname>Vasconcelos</surname><given-names>Daniel Franca</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>1</sup></xref><xref ref-type="corresp" rid="c2"/>
<role>Concepção e desenho da pesquisa</role>
<role>obtenção de dados</role>
<role>análise e interpretação dos dados</role>
<role>redação do manuscrito</role>
<role>revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
</contrib>
<aff id="aff2">
<label>1</label>
<addr-line>
<named-content content-type="city">Brasília</named-content>
<named-content content-type="state">DF</named-content>
</addr-line>
<country country="BR">Brasil</country>
<institution content-type="original">Universidade de Brasília, Faculdade de Medicina, Hospital Universitário de Brasília, Brasília, DF – Brasil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c2"><label>Correspondência:</label> <bold>Daniel Franca Vasconcelos</bold> • Universidade de Brasília. Hospital Universitário de Brasília. CEP: <postal-code>70910-900</postal-code>. Brasília, DF – Brasil E-mail: <email>dfrancav@uol.com.br</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>
<p>A estenose aórtica severa é uma entidade clínica progressiva que acompanha historicamente as descrições da anatomia patológica, da semiologia cardiovascular, da cirurgia cardíaca e das intervenções cardiovasculares percutâneas. A indicação, ainda hoje, para intervenção de troca da valva de pacientes portadores de estenose valvar aórtica severa, baseia-se no surgimento de sintomas. Com o avanço da técnica cirúrgica, sobretudo o implante percutâneo, busca-se identificar marcadores precoces de dano miocárdico que possam indicar lesões irreversíveis do miocárdio. Este artigo de revisão apresenta uma análise abrangente dos métodos de identificação do dano miocárdico em pacientes com estenose aórtica severa, incluindo avaliação clínica, eletrocardiografia, ecocardiografia, ressonância magnética cardíaca (RMC) e biomarcadores plasmáticos. Discute-se a classificação dos estágios de dano miocárdico e o momento ideal para intervenção terapêutica, com base em achados clínicos, funcionais e estruturais. Estudos recentes que foram desenhados para responder como abordar os pacientes portadores de estenose aórtica assintomáticos apresentam resultados divergentes. Desta forma, pretende-se auxiliar o clínico na decisão sobre o melhor momento para realizar a intervenção da troca valvar, considerando as particularidades de cada paciente.</p>
</abstract>
<kwd-group xml:lang="pt">
<title>Palavras-chave</title>
<kwd>Estenose da Valva Aórtica</kwd>
<kwd>Ecocardiografia</kwd>
<kwd>Imageamento por Ressonância Magnética</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="f5">
<graphic xlink:href="2675-312X-abcic-39-02-e20260054-gf01-pt.tif"/>
<p>Fluxograma proposto para orientação do manejo de pacientes portadores de estenose aórtica severa, diferenciando entre pacientes hígidos e frágeis. EAo: estenose aórtica; TAVI: intervenção aórtica valvar transcateter.</p>
</fig>
<sec sec-type="intro">
<title>Introdução</title>
<p>A estenose aórtica é a valvulopatia mais frequentemente tratada cirurgicamente na população atual.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> A entidade clínica evolui concomitantemente às descrições da anatomia patológica, da semiologia cardiovascular, da cirurgia cardíaca e, no período atual, das intervenções cardiovasculares percutâneas.</p>
<p>Em 1663, o médico francês Lazare Rivière descreveu o primeiro achado anatomopatológico da valva aórtica estenótica.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Posteriormente, Giovanni Battista Morgagni e Jean-Nicolas Corvisar descreveram a &quot;valva aórtica ossificada&quot; que não permitia o trânsito de estruturas de tamanho relevante. No século XIX (1819), Laënnec descreveu a estenose aórtica ossificada como uma entidade clínica valvar com as características semiológicas atualmente reconhecidas.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
<p>O século XX foi marcado pela descrição anatomopatológica detalhada, pelo conhecimento da fisiopatologia da doença e pelo desenvolvimento de técnicas cirúrgicas com próteses cada vez mais sofisticadas, seguido pelo desenvolvimento de intervenções percutâneas no século XXI. Atualmente, é possível estimar com base em estudos epidemiológicos ecocardiográficos o grau de progressão da estenose aórtica.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
<p>Apesar da evolução no conhecimento da fisiopatologia, a única opção terapêutica atual para a estenose valvar aórtica calcificada permanece a troca valvar.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> As diretrizes atuais, incluindo a diretriz brasileira, recomendam que a troca valvar seja indicada em pacientes com estenose valvar aórtica severa (velocidade de pico ao Doppler &gt; 4,0 m/s, gradiente médio &gt; 40 mmHg, área valvar &lt; 1,0 cm<sup>2</sup> ou área valvar indexada &lt; 0,6 cm<sup>2</sup>/m<sup>2</sup>) que apresentem sintomas, ou em pacientes com estenose severa e fração de ejeção reduzida (&lt; 50%).<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
<p>Com o surgimento das intervenções aórticas valvares transcateter (TAVI), tornou-se possível realizar a troca valvar em pacientes frágeis com risco cirúrgico elevado, para os quais a intervenção cirúrgica seria proibitiva.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> Com o entusiasmo advindo dos resultados favoráveis da intervenção percutânea e o desenvolvimento de novas técnicas de avaliação do dano miocárdico, evidenciou-se grande interesse em identificar marcadores precoces de dano miocárdico para indicar a troca valvar.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
<p>Surge, portanto, a questão central: já que a intervenção percutânea tem se mostrado segura, por que não indicar a troca valvar em pacientes com estenose severa calcificada antes que os sintomas surjam? Embora o procedimento seja considerado seguro, não é isento de riscos. Em algumas situações, pode piorar a condição clínica e a qualidade de vida, além do fato de que a durabilidade das próteses ainda não está completamente definida do ponto de vista epidemiológico.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> A mortalidade dos pacientes assintomáticos em conduta expectante é menor que 1% ao ano, bem menor do que a esperada para a troca valvar cirúrgica. Por outro lado, a durabilidade das novas próteses (endopróteses) não foi testada.</p>
<p>Em relação à conduta expectante, vários estudos tentam identificar o dano miocárdico por meio do eletrocardiograma (ECG), do teste ergométrico, redução da fração de ejeção e do strain miocárdico pela ecocardiografia, resposta do gradiente transvalvar ao ecocardiograma de estresse físico, fibrose e edema miocárdico pela ressonância magnética cardíaca (RMC), e biomarcadores plasmáticos como o peptídeo natriurético tipo B (BNP) e o N-terminal pro-BNP (NT-proBNP).<sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
<p>Apesar de todo esse processo evolutivo, estudos realizados comparando a conduta expectante com a intervenção precoce não demonstram benefícios, e permanece ainda a dificuldade em se indicar o momento ideal para a intervenção.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> A proposta deste artigo é revisar os métodos de identificação do dano miocárdico e sugerir o momento mais apropriado para a intervenção da troca valvar, antes que o dano irreversível ao miocárdio ocorra, além de propor desenhos para futuros estudos.</p>
<sec>
<title>Importância epidemiológica</title>
<p>A estenose aórtica valvar calcificada apresenta prevalência de 0,4% na população geral, aumentando para 1,7% aos 65 anos e 3,4% aos 75 anos, ou seja, aumenta significativamente com a idade acima de 65 anos.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> A valva aórtica bicúspide apresenta prevalência de 0,5% a 1,0% da população e é responsável por aproximadamente 50% das intervenções valvares, especialmente em pacientes mais jovens.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> A cirurgia de estenose valvar aórtica calcificada representa 47% de todas as cirurgias valvares realizadas.<sup><xref ref-type="bibr" rid="B12">12</xref></sup></p>
<p>Apesar dos novos conhecimentos sobre a fisiopatologia da doença valvar calcificada, até o momento não existe tratamento clínico específico para essa condição.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> O surgimento de sintomas constitui o marco temporal definido para a indicação de troca valvar. A partir do surgimento dos sintomas, a conduta expectante (sem intervenção) está associada a uma mortalidade de 50% em 2 anos.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
</sec>
<sec>
<title>Fisiopatologia</title>
<p>A doença valvar aórtica calcificada compartilha em sua fisiopatologia os mesmos mecanismos e fatores de risco da doença aterosclerótica. Na fase inicial, predomina o processo inflamatório, seguido pela fase de calcificação.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> Mais recentemente, tem sido destacado o depósito de lipoproteínas, como apoA1, apoB, apoE e lipoproteína(a), seguido de inflamação, estresse oxidativo, transição osteoblástica das células intersticiais da válvula e posteriormente calcificação.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
<p>Os fatores de risco para o desenvolvimento da doença valvar calcificada incluem: valva aórtica bicúspide, idade, sexo masculino, tabagismo, hipertensão arterial sistêmica, dislipidemia, obesidade, síndrome metabólica, diabetes mellitus, lipoproteína(a) elevada, radioterapia mediastinal, quimioterapia e doenças reumatológicas.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B16">16</xref></sup> Quanto ao risco de evolução mais rápida para estenose aórtica severa, destacam-se: idade avançada, sexo feminino, severidade hemodinâmica da estenose inicial, grau de calcificação da valva, tabagismo ativo, hipertensão arterial sistêmica não controlada, síndrome metabólica, hiperparatireoidismo, insuficiência renal crônica e lipoproteína(a) elevada.<sup><xref ref-type="bibr" rid="B16">16</xref></sup></p>
<p>Com o surgimento da intervenção percutânea em pacientes com risco cirúrgico proibitivo, abriu-se uma janela de oportunidade terapêutica para esses pacientes. Por outro lado, emergiu a tendência de realizar esse tipo de procedimento em situações nas quais o custo-benefício deve ser cuidadosamente discutido em equipe multiprofissional (Heart Team). O conceito de Heart Team ampliado inclui a participação de nefrologistas, geriatras, neurologistas, nutricionistas, pacientes e familiares, sobretudo para a população de pacientes frágeis com múltiplas morbidades.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> Apesar do risco inferior ao da cirurgia convencional, estudos em pacientes com fragilidade elevada têm mostrado resultados que questionam a indicação indiscriminada da intervenção precoce.<sup><xref ref-type="bibr" rid="B18">18</xref></sup></p>
</sec>
<sec>
<title>Adaptação à sobrecarga de pressão e dano miocárdico</title>
<p>A partir da sobrecarga de pressão mantida, observa-se aumento das miofibrilas com consequente aumento da massa muscular ventricular esquerda. Esse aumento da massa leva à redução da densidade da microcirculação coronária e ao aumento da resistência vascular coronária. A reserva coronariana fica progressivamente reduzida, inicialmente apenas durante o esforço, posteriormente também em repouso.<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
<p>Com isso, o miocárdio sofre isquemias repetidas, cujo efeito inicial é a manifestação de disfunção diastólica.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Com as isquemias recorrentes, posteriormente surgem fibroses. Inicialmente essa fibrose é intersticial, difusa e reversível após a troca valvar. Posteriormente a fibrose é substitutiva, focal e irreversível. Na sequência, ocorrem alterações da geometria funcional do ventrículo esquerdo e consequente elevação da pressão diastólica final (pressão telediastólica). Essa elevação se transmite para a pressão venosa pulmonar, com o surgimento de sintomas de congestão pulmonar (dispneia aos esforços).<sup><xref ref-type="bibr" rid="B19">19</xref></sup> A isquemia pode manifestar-se com sintomas de angina. A restrição ao fluxo de ejeção, principalmente durante o esforço, é responsável pelos sintomas de pré-síncope e síncope, sobretudo durante o esforço.<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
<p>Uma vez compreendido o mecanismo do dano miocárdico, é imperativo utilizar as ferramentas de diagnóstico disponíveis de forma racional e individualizada. Como anteriormente mencionado, ainda não existe tratamento medicamentoso para a estenose aórtica calcificada. Apesar do conhecimento sobre os mecanismos do dano miocárdico, ainda desconhecemos completamente as implicações de intervenção precoce antes do surgimento de sintomas.<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
</sec>
<sec>
<title>Identificação do dano miocárdico</title>
<sec>
<title>Avaliação clínica</title>
<p>Conforme as diretrizes atuais, a indicação da intervenção em pacientes com estenose aórtica grave deve ser realizada quando os sintomas surgirem.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Embora os sintomas clássicos (dispneia, angina e síncope) estejam bem definidos, sua identificação pode ser desafiadora em determinadas populações.</p>
<p>Pacientes com estenose aórtica secundária à valva aórtica bicúspide são tipicamente mais jovens (duas décadas menos que aqueles com estenose aórtica degenerativa), fisicamente ativos e sem comorbidades significativas.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> Nesses casos, além da história clínica e exame físico dirigido à busca de sintomas, é recomendável submeter o paciente a teste ergométrico para identificar limitações funcionais e sintomas reproduzíveis.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
<p>Já os pacientes com estenose aórtica calcificada degenerativa apresentam um perfil clínico completamente diferente. São idosos, frequentemente com problemas ortopédicos, doenças pulmonares crônicas e quadros de comprometimento cognitivo. Nesse cenário, fica muito difícil identificar adequadamente os sintomas de isquemia ou congestão.<sup><xref ref-type="bibr" rid="B21">21</xref></sup></p>
<p>Independentemente do perfil, os pacientes assintomáticos com estenose aórtica severa devem ser acompanhados periodicamente a cada 3 a 6 meses, na expectativa de identificar sintomas emergentes ou alterações no ECG e no ecocardiograma.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
</sec>
<sec>
<title>Eletrocardiograma</title>
<p>Na avaliação do dano miocárdico, o ECG pode fornecer informações importantes relacionadas à sobrecarga do ventrículo esquerdo. O ECG com achados sugestivos de sobrecarga ventricular esquerda (hipertrofia ventricular esquerda) em pacientes assintomáticos com estenose aórtica severa estimada pelo gradiente transvalvar ao ecocardiograma representa um sinal de alerta (luz amarela) que justifica acompanhamento intensificado.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> Estudos de marcadores de prognóstico sugerem que a hipertrofia ventricular, identificada pelo ECG, pelo ecocardiograma ou pela RMC, representa uma evolução pior em comparação aos pacientes que não a apresentam. A presença de arritmia, particularmente a fibrilação atrial, pode resultar do aumento da pressão de enchimento ventricular secundária à disfunção diastólica e à consequente sobrecarga atrial esquerda, podendo indicar dano miocárdico.</p>
</sec>
<sec>
<title>Teste ergométrico</title>
<p>O teste ergométrico possui papel importante na avaliação de pacientes assintomáticos com estenose aórtica severa. Esse teste pode evidenciar sintomas típicos (dispneia desproporcional ao esforço, angina precordial ou síncope) que não eram detectados no repouso, em até 30% dos indivíduos ditos assintomáticos, orientando assim a decisão por intervenção. Além dos sintomas, a resposta hipotensiva ao esforço, a isquemia no ECG ou o surgimento de arritmias malignas também são indicadores de maior gravidade, com risco relativo mais de 7 vezes maior em relação aos pacientes com resultados normais.<sup><xref ref-type="bibr" rid="B23">23</xref></sup></p>
</sec>
<sec>
<title>Ecocardiografia</title>
<p>O ecocardiograma transtorácico é o método de escolha para avaliação da anatomia da valva aórtica, quantificação da severidade da estenose, identificação de disfunções valvares associadas, disfunção diastólica, pressão de enchimento ventricular (E/e′), estimativa da fração de ejeção do ventrículo esquerdo, avaliação da função do ventrículo direito e estimativa da pressão arterial pulmonar.<sup><xref ref-type="bibr" rid="B24">24</xref></sup> É importante notar que, embora o ponto de corte tradicional para disfunção sistólica seja uma fração de ejeção de 50%, valores acima desse limiar, mas com declínio progressivo significativo (&gt; 10%), podem, à semelhança dos pacientes oncológicos em quimioterapia, representar dano miocárdico relevante e justificar a troca valvar.<sup><xref ref-type="bibr" rid="B25">25</xref></sup></p>
<p>A estenose aórtica muito severa (Vmax &gt; 5 m/s) ou a progressão da gravidade da estenose (&gt; 0,3 m/s/ano) estão associadas ao surgimento de sintomas e à piora da mortalidade no primeiro ano.<sup><xref ref-type="bibr" rid="B24">24</xref></sup> A diretriz europeia considera indicação de intervenção classe IIa para essa condição.</p>
<p>A avaliação seriada com redução progressiva da função ventricular é particularmente informativa. Por exemplo, um paciente com fração de ejeção inicial de 68% que apresenta redução evolutiva para 60% demonstra uma queda de mais de 10%, podendo significar dano miocárdico relevante em progressão.<sup><xref ref-type="bibr" rid="B25">25</xref></sup></p>
<p>A impedância ventrículo-arterial (VZA) representa um marcador de dano miocárdico que utiliza a pressão arterial sistólica (PAS) somadà ao gradiente médio transvalvar (Gmédio) dividido pelo volume sistólico indexado pela superfície corpórea (VSi): VZA = (PAS + Gmédio) / VSi. Valores maiores do que 4,5 apresentam importância prognóstica para indicação de troca valvar.<sup><xref ref-type="bibr" rid="B26">26</xref></sup></p>
<p>O átrio esquerdo aumenta de forma proporcional à disfunção diastólica, representando a evolução crônica de sobrecarga atrial. O aumento do átrio esquerdo e a elevação da pressão sistólica da artéria pulmonar representam sinais de dano miocárdico, assim como a disfunção do ventrículo direito e a insuficiência tricúspide.<sup><xref ref-type="bibr" rid="B27">27</xref></sup></p>
<p>Genereux e colaboradores analisaram os pacientes do estudo PARTNER 2, que foram agrupados e classificados de acordo com a presença ou ausência de dano cardíaco detectado por ecocardiografia antes da troca valvar aórtica: sem dano cardíaco extravalvar (estágio 0), dano no ventrículo esquerdo (estágio 1), dano no átrio esquerdo ou válvula mitral (estágio 2), dano na vasculatura pulmonar ou válvula tricúspide (estágio 3) ou dano no ventrículo direito (estágio 4). Entre os 1.661 pacientes com dados ecocardiográficos, a mortalidade em 1 ano foi de 4,4% no estágio 0, 9,2% no estágio 1, 14,4% no estágio 2, 21,3% no estágio 3 e 24,5% no estágio 4 (p para tendência &lt; 0,0001). A extensão do dano cardíaco foi independentemente associada a maior mortalidade após a troca valvar aórtica (<italic>hazard ratio</italic> 1,46 para cada incremento no estágio, intervalo de confiança de 95% 1,27–1,67, p &lt; 0,0001). Esses resultados sugerem que, afora os estágios 0 e 1, os demais demonstram alterações estruturais e funcionais cujos sintomas provavelmente estavam presentes e que tiveram importância prognóstica. Mais uma vez, a soma de marcadores de dano miocárdico sugere que a troca valvar antes do surgimento dos sintomas possa ser uma conduta aceitável, embora os resultados até agora sejam controversos.<sup><xref ref-type="bibr" rid="B28">28</xref></sup></p>
</sec>
<sec>
<title>Strain longitudinal global</title>
<p>Ainda na avaliação ecocardiográfica, pode-se inserir a avaliação do strain longitudinal global do miocárdio, que se mostra uma ferramenta mais sensível para identificar disfunção sistólica precoce.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Embora o ponto de corte tradicional para disfunção ventricular pelo strain seja −17% e para pacientes com estenose aórtica seja −14%, a redução progressiva do strain também pode ser interpretada como evidência de dano miocárdico progressivo.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup> Estudos correlacionam a redução do strain miocárdico com o surgimento de sintomas. O strain reduzido também tem valor prognóstico após a troca valvar.<sup><xref ref-type="bibr" rid="B29">29</xref></sup></p>
<p>O strain atrial é uma ferramenta adicional que pode ser utilizada por aqueles que possuem equipamentos com esse recurso. Embora os dados sejam controversos, de fato o strain atrial identifica a disfunção atrial antes do remodelamento e pode prever o surgimento de fibrilação atrial durante a evolução da doença e no pós-operatório<sup><xref ref-type="bibr" rid="B30">30</xref></sup> (<xref ref-type="fig" rid="f6">Figura 1</xref>).</p>
<fig id="f6">
<label>Figura 1</label>
<caption><title>Ecocardiograma transtorácico bidimensional com Doppler em cores demonstrando estenose aórtica severa. No alto à direita: corte paraesternal longitudinal mostrando ventrículo esquerdo hipertrofiado e valva aórtica bem calcificada; à direita abaixo: velocidade transvalvar &gt; 4,5 m/s e gradiente médio = 50 mmHg; à esquerda: mapa do strain longitudinal global normal = 21,1%.</title></caption>
<graphic xlink:href="2675-312X-abcic-39-02-e20260054-gf02-pt.tif"/>
</fig>
</sec>
<sec>
<title>Ecocardiograma de estresse</title>
<p>Apesar das diretrizes atuais não recomendarem a ecocardiografia de estresse como ferramenta de estratificação em pacientes assintomáticos com estenose aórtica severa,<sup><xref ref-type="bibr" rid="B5">5</xref></sup> a sua utilização durante o estresse físico ou farmacológico (dobutamina) para avaliação do gradiente transvalvar, do traçado eletrocardiográfico e da resposta da função ventricular continua sendo investigada.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Estudos comparando pacientes com teste de estresse positivo versus negativo, posteriormente submetidos à intervenção valvar, mostram variabilidade nos resultados, sem diferenças significativas e consistentes no prognóstico a longo prazo entre os grupos.<sup><xref ref-type="bibr" rid="B31">31</xref></sup> O ecocardiograma de estresse no manejo dos pacientes assintomáticos com estenose aórtica severa ainda necessita de estudos futuros para ser definido.</p>
</sec>
</sec>
<sec>
<title>Ressonância magnética cardíaca</title>
<p>A RMC emergiu como um importante marcador não invasivo de dano miocárdico em estenose aórtica severa.<sup><xref ref-type="bibr" rid="B32">32</xref></sup> Além de avaliar a gravidade da estenose com resultados comparáveis ao ecocardiograma, atualmente é possível, por meio dos mapas T1 nativo, identificar e quantificar lesões de fibrose intersticial difusa miocárdica que podem ser parcialmente reversíveis após a troca valvar. O realce tardio com gadolínio permite a identificação de pontos de fibrose focal, habitualmente irreversível, e um importante indicador para a troca precoce da valva.<sup><xref ref-type="bibr" rid="B32">32</xref>,<xref ref-type="bibr" rid="B33">33</xref></sup></p>
<p>Alguns estudos iniciais sugeriram que antecipar a troca valvar em pacientes com alterações fibróticas detectadas à RMC pudesse modificar favoravelmente o desfecho clínico e funcional.<sup><xref ref-type="bibr" rid="B34">34</xref></sup> Porém, o estudo randomizado EVOLVED, publicado recentemente com 224 pacientes, não demonstrou benefícios em antecipar a troca valvar antes do surgimento de sintomas, mesmo na presença de fibrose miocárdica detectada à RMC.<sup><xref ref-type="bibr" rid="B35">35</xref></sup> De forma semelhante, Myhr e colaboradores, comparando 42 pacientes sintomáticos com 80 pacientes assintomáticos, mostraram que a presença de fibrose miocárdica identificada com RMC com realce tardio não mostrou diferenças significativas em relação à evolução após a troca valvar<sup><xref ref-type="bibr" rid="B36">36</xref></sup> (<xref ref-type="fig" rid="f7">Figura 2</xref>; <xref ref-type="other" rid="f8">Vídeo 1</xref>).</p>
<fig id="f7">
<label>Figura 2</label>
<caption><title>Ressonância magnética cardíaca em paciente com estenose aórtica severa. O realce tardio com gadolínio mostra padrão de fibrose subendocárdica focal. Essas alterações representam evidência de dano miocárdico estrutural irreversível (imagem gentilmente cedida pelo Dr. Luiz Augusto Quaglia).</title></caption>
<graphic xlink:href="2675-312X-abcic-39-02-e20260054-gf03-pt.tif"/>
</fig>
<media id="f8" mime-subtype="mp4" mimetype="video" xlink:href="2675-312X-abcic-39-02-e20260054-m01-pt.mp4">
<label>Vídeo 1</label>
<caption><title>Ressonância magnética cardíaca demonstrando estenose aórtica grave com remodelamento estrutural miocárdico e fibrose focal. Cortesia do Dr. Luiz Augusto Quaglia. Disponível em: <ext-link ext-link-type="uri" xlink:href="http://abcimaging.org/supplementary-material/2026/3902/ABCImag-2026-0054_AR_Video_1.mp4">http://abcimaging.org/supplementary-material/2026/3902/ABCImag-2026-0054_AR_Video_1.mp4</ext-link></title></caption>
</media>
<p>Por outro lado, também publicado recentemente, o estudo randomizado por Généreux e colaboradores (EARLY TAVR), embora com algumas limitações metodológicas, avaliou um número significativamente maior de pacientes (901 pacientes), sugerindo resultado favorável à intervenção precoce percutânea em pacientes assintomáticos com estenose aórtica severa.<sup><xref ref-type="bibr" rid="B36">36</xref></sup> Embora a conclusão tenha sido favorável, a mortalidade e o prognóstico foram semelhantes. A intervenção reduziu o desfecho de internação. Boa parte dessas internações foi decorrente de descompensação no grupo de acompanhamento clínico, em pacientes que foram submetidos à intervenção nos 90 dias subsequentes. Resultados semelhantes foram encontrados no estudo AVATAR (Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis).<sup><xref ref-type="bibr" rid="B37">37</xref></sup></p>
</sec>
<sec>
<title>Biomarcadores plasmáticos</title>
<p>Níveis elevados de BNP e NT-proBNP correlacionam-se com aumento da pressão de enchimento ventricular e predizem pior prognóstico em estenose aórtica severa.<sup><xref ref-type="bibr" rid="B38">38</xref></sup> Valores elevados podem traduzir dano miocárdico com consequente insuficiência diastólica.<sup><xref ref-type="bibr" rid="B38">38</xref></sup> Da mesma forma que outros marcadores de dano miocárdico, talvez a piora evolutiva nas avaliações seriadas, associada a outros marcadores, possa indicar a antecipação da troca valvar.</p>
<p>Outros marcadores bioquímicos também mostraram valor prognóstico no resultado cirúrgico na avaliação pré-operatória. A troponina T de alta sensibilidade possui valor prognóstico importante. Elevações de troponina T, mesmo que discretas, em pacientes com estenose aórtica severa correlacionam-se com pior evolução clínica e maior risco de eventos adversos.<sup><xref ref-type="bibr" rid="B39">39</xref></sup> Esse marcador pode identificar miocárdio com dano celular estrutural já presente.<sup><xref ref-type="bibr" rid="B39">39</xref></sup> A osteopontina, uma glicoproteína secretada por células ligadas a processos inflamatórios e de remodelamento, mostrou-se marcador de dano miocárdico irreversível. Estudos demonstram que osteopontina prediz resultado clínico adverso em pacientes após tratamento de estenose aórtica severa com TAVI.<sup><xref ref-type="bibr" rid="B40">40</xref></sup> A anexina A1, estudada em fluido pericárdico de pacientes com estenose aórtica severa, mostrou-se marcador de fibrilação atrial associada a estenose aórtica, representando um marcador de remodelamento atrial.<sup><xref ref-type="bibr" rid="B41">41</xref></sup> A atividade plasmática de ACE2 mostrou-se associada à fibrose miocárdica severa e prediz mortalidade em pacientes com estenose aórtica.<sup><xref ref-type="bibr" rid="B42">42</xref></sup> Sua elevação marca processos de remodelamento miocárdico patológico com desenvolvimento de fibrose.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
<p>Embora os biomarcadores identifiquem pacientes com prognóstico pior, as diretrizes atuais ainda não mencionam o papel desses biomarcadores na tomada de decisão.</p>
</sec>
</sec>
<sec sec-type="discussion">
<title>Discussão: Quando intervir?</title>
<p>Apesar das múltiplas ferramentas diagnósticas disponíveis e dos inúmeros estudos publicados, o momento ideal para realizar a troca valvar aórtica (<italic>to op</italic>) permanece controverso e sem consenso absoluto (<italic>not to op</italic>).<sup><xref ref-type="bibr" rid="B7">7</xref></sup> No mundo real, temos observado indicações cada vez mais frequentes de colocação de TAVI em pacientes com menos de 65 anos. Apesar da segurança do procedimento, os resultados a longo prazo mostram que a mortalidade é maior no grupo da intervenção percutânea. A <xref ref-type="fig" rid="f5">Figura Central</xref> apresenta uma proposta de fluxograma para orientação do acompanhamento dos pacientes assintomáticos com estenose aórtica severa.</p>
<p>A experiência clínica sugere prudência e bom senso na tomada de decisão. Em pacientes jovens, hígidos e assintomáticos, portadores de estenose valvar aórtica calcificada severa, recomenda-se acompanhamento próximo com consultas a cada 3 a 6 meses, incluindo:</p>
<list list-type="bullet">
<list-item><p>ECG seriado</p></list-item>
<list-item><p>Ecocardiograma com avaliação de fração de ejeção e strain miocárdico</p></list-item>
<list-item><p>Teste ergométrico (se adequado para o perfil clínico do paciente)</p></list-item>
<list-item><p>Biomarcadores plasmáticos (BNP/NT-proBNP; troponina T ultrassensível)</p></list-item>
<list-item><p>RMC com mapas T1 e T2 e realce tardio com gadolínio (menos frequentemente, em situações selecionadas)</p></list-item>
</list>
<p>Mudanças evolutivas com piora da função ventricular, seja pela fração de ejeção ou pelo strain miocárdico, aumento do átrio esquerdo, progressão da estenose e sinais de elevação da pressão arterial pulmonar, aliados ao teste ergométrico alterado (seja por isquemia, queda da pressão ou arritmias malignas), talvez representem elementos para recomendação de troca valvar.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
<p>Em pacientes idosos com fragilidade que dificulte a adequada avaliação dos sintomas, além dos parâmetros listados acima (com exceção do teste ergométrico, que pode ser contraindicado), sugere-se incorporar à avaliação o conceito multidimensional de fragilidade (Heart Team ampliado) para auxiliar na decisão entre realizar intervenção valvar eletiva ou condução clínica com acompanhamento rigoroso.<sup><xref ref-type="bibr" rid="B43">43</xref></sup></p>
<p>Para todos os pacientes, a classificação de dano miocárdico proposta por Genereux e colaboradores, após avaliação da população do estudo PARTNER, pode ajudar na identificação dos estágios iniciais do dano miocárdico e justificar a indicação cirúrgica anteriormente descrita. A classificação deve ser aplicada lembrando que, com exceção do estágio 0, todos os demais estágios associam-se a pior prognóstico, justificando maior vigilância e antecipação da intervenção quando apropriado.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
</sec>
<sec sec-type="conclusions">
<title>Conclusão</title>
<p>A estenose aórtica severa representa um desafio na condução clínica atual, caracterizado pela possibilidade técnica de intervenção percutânea segura, porém sem clareza absoluta sobre o momento ideal para sua realização. O avanço no conhecimento fisiopatológico da doença e o desenvolvimento de ferramentas diagnósticas sofisticadas (ecocardiografia com strain, RMC com mapeamento tecidual e biomarcadores específicos) permitem identificar dano miocárdico em seus estágios progressivos antes do surgimento dos sintomas. Embora o racional fisiopatológico aponte para a intervenção baseada na identificação de marcadores de dano miocárdico, os estudos realizados até o momento apresentam resultados controversos. As características da expressão fenotípica da doença, que definem o remodelamento ventricular, a piora da função diastólica e sistólica, o remodelamento atrial e a reação da microcirculação pulmonar, podem diferenciar o momento do surgimento dos sintomas. São necessários estudos bem desenhados com resultados consistentes para incorporar a conduta de intervenção nas diretrizes.</p>
<p>Recomenda-se abordagem individualizada e estratificada pelo risco, considerando: perfil clínico do paciente (jovem versus idoso, frágil versus hígido), presença e progressão de marcadores de dano miocárdico estrutural e funcional, comorbidades associadas e preferências informadas do paciente. A decisão por intervalo de seguimento mais próximo versus intervenção eletiva deve ser baseada em discussão multidisciplinar no contexto do Heart Team ampliado. Na população idosa, assintomática ou sintomática, com fenótipo de hipertrofia do ventrículo esquerdo, cabe sempre considerar a possibilidade de doença amiloide.</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>
<ack>
<title>Agradecimentos</title>
<p>O autor agradece às equipes de ecocardiografia e RMC que contribuíram para a compilação das imagens clínicas apresentadas neste manuscrito.</p>
</ack>
</back>
</sub-article>
</article>
