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	<front>
		<journal-meta>
			<journal-id journal-id-type="publisher-id">abcimg</journal-id>
			<journal-title-group>
				<journal-title>ABC Imagem Cardiovascular</journal-title>
				<abbrev-journal-title abbrev-type="publisher">Arq Bras Cardiol: Imagem cardiovasc.</abbrev-journal-title>
			</journal-title-group>
			<issn pub-type="epub">2675-312X</issn>
			<publisher>
				<publisher-name>Sociedade Brasileira de Cardiologia</publisher-name>
			</publisher>
		</journal-meta>
		<article-meta>
			<article-id pub-id-type="doi">10.36660/abcimg.20240134i</article-id>
			<article-id pub-id-type="publisher-id">abcimg.20240134i</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Original Article</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Mitral Annulus Diameter's Relevance in the Diagnosis of Atrial Etiology in Mitral Regurgitation: A Comparative Analysis</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0003-0842-8223</contrib-id>
					<name>
						<surname>Souza</surname>
						<given-names>Alexandre Costa</given-names>
					</name>
					<role>Conception and design of the research</role>
					<role>acquisition of data</role>
					<role>analysis and interpretation of the data and statistical analysis</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
					<xref ref-type="corresp" rid="c1"/>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-1375-785X</contrib-id>
					<name>
						<surname>Junqueira</surname>
						<given-names>Bruna de Mattos Ivo</given-names>
					</name>
					<role>Conception and design of the research</role>
					<role>writing of the manuscript</role>
					<role>critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-3275-9762</contrib-id>
					<name>
						<surname>Drubi</surname>
						<given-names>Stephanie de Azevedo</given-names>
					</name>
					<role>acquisition of data</role>
					<role>writing of the manuscript</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-3676-5502</contrib-id>
					<name>
						<surname>Gomes</surname>
						<given-names>Laila Caroline</given-names>
					</name>
					<role>writing of the manuscript</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0003-2425-4569</contrib-id>
					<name>
						<surname>Freire</surname>
						<given-names>Marcus Vinicius</given-names>
					</name>
					<role>critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0007-3613-5790</contrib-id>
					<name>
						<surname>Pinheiro</surname>
						<given-names>Priscila</given-names>
					</name>
					<role>acquisition of data</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-7440-6930</contrib-id>
					<name>
						<surname>Basile</surname>
						<given-names>Alessandra Ghattas</given-names>
					</name>
					<role>acquisition of data</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-0656-8399</contrib-id>
					<name>
						<surname>Sales</surname>
						<given-names>Marco André Moraes</given-names>
					</name>
					<role>writing of the manuscript</role>
					<role>critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-1465-2339</contrib-id>
					<name>
						<surname>Guedes</surname>
						<given-names>Ricardo André Sales Pereira</given-names>
					</name>
					<role>writing of the manuscript</role>
					<role>critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-5129-7639</contrib-id>
					<name>
						<surname>Macêdo</surname>
						<given-names>Carolina Thé</given-names>
					</name>
					<role>critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<aff id="aff1">
					<label>1</label>
					<institution content-type="orgname">Hospital São Rafael/ Rede DOr</institution>
					<addr-line>
						<named-content content-type="city">Salvador</named-content>
						<named-content content-type="state">BA</named-content>
					</addr-line>
					<country country="BR">Brazil</country>
					<institution content-type="original">Hospital São Rafael/ Rede DOr, Salvador, BA – Brazil</institution>
				</aff>
				<aff id="aff2">
					<label>2</label>
					<institution content-type="orgname">Instituto D’Or de ensino e pesquisa</institution>
					<addr-line>
						<named-content content-type="city">Salvador</named-content>
						<named-content content-type="state">BA</named-content>
					</addr-line>
					<country country="BR">Brazil</country>
					<institution content-type="original">Instituto D’Or de ensino e pesquisa, Idor, Salvador, BA – Brazil</institution>
				</aff>
			</contrib-group>
			<author-notes>
				<corresp id="c1">
					<label>Mailing Address:</label><bold>Alexandre Costa Souza</bold> • Hospital São Rafael. Avenida São Rafael. Postal Code: <postal-code>41253-190</postal-code>. Salvador, BA – Brazil E-mail: <email>alexandrecostahsr@gmail.com</email>
				</corresp>
				<fn fn-type="conflict">
					<label>Potential Conflict of Interest</label>
					<p>No potential conflict of interest relevant to this article was reported.</p>
				</fn>
				<fn fn-type="edited-by">
					<label>Editor responsible for the review:</label>
					<p>Marcelo Tavares</p>
				</fn>
			</author-notes>
			<pub-date date-type="pub" publication-format="electronic">
				<day>28</day>
				<month>03</month>
				<year>2025</year>
			</pub-date>
			<pub-date date-type="collection" publication-format="electronic">
				<year>2025</year>
			</pub-date>
			<volume>38</volume>
			<issue>1</issue>
			<elocation-id>e20240134</elocation-id>
			<history>
				<date date-type="received">
					<day>15</day>
					<month>01</month>
					<year>2025</year>
				</date>
				<date date-type="rev-recd">
					<day>17</day>
					<month>01</month>
					<year>2025</year>
				</date>
				<date date-type="accepted">
					<day>26</day>
					<month>01</month>
					<year>2025</year>
				</date>
			</history>
			<permissions>
				<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
					<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
				</license>
			</permissions>
			<abstract>
				<title>Abstract</title>
				<sec>
					<title>Background:</title>
					<p>Atrial Functional Mitral Regurgitation (FMR) is defined by mitral annular dilation and functional alterations without structural impairment of the leaflets or subvalvular apparatus. It is associated with higher cardiovascular mortality, being often characterized as an exclusion diagnosis due to the absence of more precise diagnostic criteria. Therefore, it is crucial to identify markers that distinguish it from other Mitral Regurgitation (MR) types.</p>
				</sec>
				<sec>
					<title>Objective:</title>
					<p>To assess the accuracy of the intercommissural diameter of the mitral annulus and its value indexed to body surface area in differentiating atrial etiology in patients with MR.</p>
				</sec>
				<sec>
					<title>Methods:</title>
					<p>This is an observational cross-sectional study with 109 patients diagnosed with moderate or severe MR. Data were obtained between October 2022 and January 2024, from transesophageal echocardiograms performed at a referral hospital in the city of Salvador-BA.</p>
				</sec>
				<sec>
					<title>Results:</title>
					<p>The mean age was 69 ± 15, with 67 males and 28 cases of atrial etiology. The comparison between patients with MR of Atrial etiology versus Non-atrial etiology revealed significantly increased diameters of the intercommissural mitral annulus and its indexed value, with considerably larger diameters in the Atrial group (p = 0.009; 95% CI: 0.501 to 3.507). The receiver operating characteristic (ROC) curve analysis identified an optimal cut-off value of 20.8750, in which the sensitivity and specificity were 67.9%.</p>
				</sec>
				<sec>
					<title>Conclusion:</title>
					<p>Indexing the mitral annular diameter to the body surface area improves diagnostic accuracy in identifying the atrial etiology of MR compared to diameter alone, supporting its potential role in more comprehensive diagnostic algorithms.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="en">
				<title>Keywords:</title>
				<kwd>Mitral Valve Insufficiency</kwd>
				<kwd>Heart Failure</kwd>
				<kwd>Atrial Fibrillation</kwd>
			</kwd-group>
			<counts>
				<fig-count count="4"/>
				<table-count count="4"/>
				<equation-count count="0"/>
				<ref-count count="29"/>
			</counts>
		</article-meta>
	</front>
	<body>
		<sec sec-type="intro">
			<title>Introduction</title>
			<p>Mitral Regurgitation (MR) is one of the most prevalent valvular diseases in the world, with continuous advances in the understanding of its pathophysiology, diagnosis, and management.<sup><xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B4">4</xref></sup> Among its etiological presentations, Functional Mitral Regurgitation (FMR) of atrial etiology stands out for its clinical relevance, especially in the context of Atrial Fibrillation (AF) and Heart Failure with preserved Ejection Fraction (HFpEF).<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> It is characterized by mitral annulus dilation and functional alterations of the valve without structural compromise of the leaflets or the subvalvular apparatus. A detailed evaluation of the left atrium and mitral annulus is key for establishing a diagnosis.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> The increasing prevalence of AF and HFpEF highlights the importance of more accurate diagnostic and therapeutic strategies for FMR.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> This condition is associated with increased mortality, and interventions such as rhythm control have shown a potential to reduce its frequency.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
			<p>While AF is commonly associated with FMR, studies suggest that left ventricular diastolic dysfunction also contributes to atrial remodeling, playing a role in the development of this valvular disease.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup> Its pathophysiological mechanisms include significant anatomical and functional changes. The phenomenon known as hamstringing, characterized by restricted movement of the posterior mitral leaflet, and bending, which is a pathological deformation of the leaflet under hemodynamic stress, directly impairs valve functionality. Moreover, changes in the ratio between the leaflets and mitral annulus area, associated with atrial tethering caused by posterior displacement of the annulus in response to left atrial enlargement, contribute to mitral coaptation deficiency. These changes show that FMR results from combined valve and atrial remodeling, and is not restricted to the annular dimensions. These processes directly impact valve coaptation and worsen the severity of MR.<sup><xref ref-type="bibr" rid="B10">10</xref>-<xref ref-type="bibr" rid="B12">12</xref></sup></p>
			<fig id="f1">
				<caption>
					<title>AUC: area under the curve; MR: Mitral Regurgitation.</title>
				</caption>
				<graphic xlink:href="2675-312X-abcimg-38-01-e20240134-gf01.tif"/>
			</fig>
			<p>Although the literature extensively discusses the pathophysiology of MR and its associated clinical and echocardiographic findings, there is a lack of studies focused on refining diagnostic criteria for this specific condition.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Given this gap, the present study aimed to determine the accuracy of the intercommissural diameter of the mitral annulus and its value indexed to body surface area, as measured by transesophageal echocardiography, in differentiating atrial etiology in patients with MR.</p>
		</sec>
		<sec sec-type="methods">
			<title>Method</title>
			<p>This is an observational, cross-sectional study, with 109 patients with moderate or severe MR. Echocardiographic images were obtained by transesophageal echocardiography at a referral hospital located in Salvador-BA, in the period between October 2022 and January 2024.</p>
			<sec>
				<title>Patients</title>
				<p>Patients were selected through a convenience sample based on clinical indications for transesophageal echocardiography as determined by the attending cardiologists. The indication was based on clinical criteria, considering the need for a detailed assessment of the mitral valve and the severity of regurgitation for therapeutic planning. All patients with moderate or severe MR who underwent transesophageal echocardiography between October 2022 and January 2024, in either outpatient or hospital settings, were included. The exclusion criterion was the presence of only mild MR on transesophageal echocardiography or the presence of a prosthetic mitral valve.</p>
				<p>The sample consisted of two groups: patients with MR of Atrial etiology (N = 25) and with Non-atrial etiology (N = 84). Between the groups, significant differences were observed in clinical and echocardiographic characteristics. The Atrial group had a higher median age (77 years, 95% CI: 73-84)than the Non-atrial group (67 years, 95% CI: 60-71; <italic>p</italic> &lt; 0.001), in addition to a higher prevalence of AF (72% vs. 34%; <italic>p</italic> &lt; 0.001). 68% vs. 67%, 95% CI: 60-71; <italic>p</italic> &lt; 0.001). The Non-atrial group showed a higher proportion of male patients (68% vs. 68%, 95% CI: 60-71; p &lt; 0.001). 42%; <italic>p</italic> = 0.019).</p>
				<p>From an echocardiographic point of view, patients in the Atrial group had larger diameters in the mitral annulus, both in linear measurement (46.04 mm vs. 44.37 mm; <italic>p</italic> = 0.012) and in the index adjusted for body surface area (21.63 ± 1.86 vs. 19.36 ± 2.48; <italic>p</italic> &lt; 0.001). Additionally, the left atrial volume was significantly greater in the atrial group (59.02 ml/m²vs. 38.00 ml/m²; <italic>p</italic> = 0.08). Other characteristics, such as Left Ventricular Ejection Fraction (LVEF) and E/e’ ratio, were not significantly different between the groups (<italic>p</italic> &gt; 0.05).</p>
			</sec>
			<sec>
				<title>Echocardiogram</title>
				<p>Transesophageal echocardiography was chosen due to its superior ability to assess both the anatomical and functional aspects of the mitral valve.<sup><xref ref-type="bibr" rid="B13">13</xref>-<xref ref-type="bibr" rid="B15">15</xref></sup> Echocardiographic images were obtained following a standardized protocol with high-resolution equipment (GE Healthcare, E95).</p>
				<p>The intercommissural diameter of the mitral annulus was measured using the linear dimension of the intercommissural slice, obtained in a mid-esophageal view at 60º. In addition, two experienced evaluators classified MR into two groups: Atrial and Non-atrial, according to current guidelines. In cases of disagreement, a third evaluator provided a final classification.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
				<p>The diagnosis of FMR was based on the following criteria: a dilated mitral annulus on transthoracic echocardiography (&gt; 35 mm in systole on the longitudinal parasternal view), absence of primary mitral valve disease, significant left atrial dilation (indexed volume &gt; 42 ml/m²) and absence of significant ventricular dysfunction (LVEF: &gt; 45%, assessed using the Simpson method).<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B16">16</xref></sup> These criteria were applied to differentiate FMR cases and guide the analysis of the intercommissural diameter relevance as a diagnostic marker.</p>
			</sec>
			<sec>
				<title>Statistical Analysis</title>
				<p>Statistical analysis was performed using IBM SPSS Statistics for Windows, version 27.0 (IBM Corp, Armonk, NY, USA). In the descriptive analysis, categorical variables were presented as frequencies and percentages, while continuous variables were described by mean and standard deviation. The normality of continuous variables was assessed using the Shapiro-Wilk test, adopting a <italic>p-value</italic>&gt; 0.05 as the criterion for normality.</p>
				<p>Comparisons between the Atrial and Non-Atrial groups followed different approaches depending on the variable's nature. For categorical variables, the Pearson's chi-square test was applied. Continuous variables with normal distribution were analyzed using the Student's t-test for independent samples, with the effect size of significant differences being quantified by Cohen's d. In cases of non-normal distribution, the Mann-Whitney's <italic>U</italic> test was used to compare groups. A 95% confidence level was adopted for all tests.</p>
				<p>ROC curve analysis was performed to evaluate the diagnostic accuracy of mitral annular diameter and its indexed value in differentiating Atrial from Non-atrial MR. The C statistic was used as a quantitative measure of accuracy, with values above 0.7 indicating good discriminatory capacity. The Youden index was applied to determine the optimal cutoff point for identifying atrial MR based on the indexed mitral annulus.</p>
			</sec>
		</sec>
		<sec sec-type="results">
			<title>Results</title>
			<p>A total of 109 patients were evaluated, with a mean age of 69 ± 15 years. Most participants were male, with a total of 67 men (61.4%). In the sample, 44% had a known diagnosis of AF, including 20 patients in the Atrial group and 28 in the Non-atrial group. The prevalence of AF differed significantly between the groups (<italic>p</italic> &lt; 0.001) (<xref ref-type="table" rid="t1">Table 1</xref>).</p>
			<table-wrap id="t1">
				<label>Table 1</label>
				<caption>
					<title>Demographic and clinical data</title>
				</caption>
				<table frame="hsides" rules="groups">
					<colgroup width="25%">
						<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"/>
							<th align="center" valign="middle">Atrial group (N=28)</th>
							<th align="center" valign="middle">Non-atrial group (N=84)</th>
							<th align="center" valign="middle">p-value</th>
						</tr>
					</thead>
					<tbody style="border-bottom: thin solid; border-color: #000000">
						<tr>
							<td align="left" valign="middle">Age - years</td>
							<td align="center" valign="middle">77 (73-84)</td>
							<td align="center" valign="middle">67 (60-71)</td>
							<td align="center" valign="middle">&lt; 0.001</td>
						</tr>
						<tr style="background-color:#E8CCBF;">
							<td align="left" valign="middle">Gender: Male, n (%)</td>
							<td align="center" valign="middle">12 (48%)</td>
							<td align="center" valign="middle">55 (65%)</td>
							<td align="center" valign="middle">0.19</td>
						</tr>
						<tr>
							<td align="left" valign="middle">AF, n (%)</td>
							<td align="center" valign="middle">20 (72%)</td>
							<td align="center" valign="middle">28 (33%)</td>
							<td align="center" valign="middle">&lt; 0.001</td>
						</tr>
						<tr style="background-color:#E8CCBF;">
							<td align="left" valign="middle">Dyslipidemia, n (%)</td>
							<td align="center" valign="middle">21 (75%)</td>
							<td align="center" valign="middle">42 (50%)</td>
							<td align="center" valign="middle">0.025</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Stroke, n (%)</td>
							<td align="center" valign="middle">05 (18%)</td>
							<td align="center" valign="middle">13 (16%)</td>
							<td align="center" valign="middle">0.805</td>
						</tr>
						<tr style="background-color:#E8CCBF;">
							<td align="left" valign="middle">Previous Coronary Artery Disease, n (%)</td>
							<td align="center" valign="middle">07 (25%)</td>
							<td align="center" valign="middle">34 (40%)</td>
							<td align="center" valign="middle">0.141</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Diabetes Mellitus, n (%)</td>
							<td align="center" valign="middle">07 (25%)</td>
							<td align="center" valign="middle">31 (37%)</td>
							<td align="center" valign="middle">0.204</td>
						</tr>
						<tr style="background-color:#E8CCBF;">
							<td align="left" valign="middle">Systemic Arterial Hypertension, n (%)</td>
							<td align="center" valign="middle">22 (78%)</td>
							<td align="center" valign="middle">48 (57%)</td>
							<td align="center" valign="middle">0.066</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Chronic Renal Failure, n (%)</td>
							<td align="center" valign="middle">05 (18%)</td>
							<td align="center" valign="middle">14 (17%)</td>
							<td align="center" valign="middle">0.976</td>
						</tr>
						<tr style="background-color:#E8CCBF;">
							<td align="left" valign="middle">Weight (kg), n (%)</td>
							<td align="center" valign="middle">72.04 (70-74)</td>
							<td align="center" valign="middle">73.51 (72-75)</td>
							<td align="center" valign="middle">0.632</td>
						</tr>
					</tbody>
				</table>
				<table-wrap-foot>
					<fn id="TFN1">
						<p>AF: Atrial Fibrillation.</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
			<p>Patients were categorized based on MR etiology, with 28 (25%) assigned to the Atrial MR group and 81 (75%) to the Non-atrial group. The remaining participants, corresponding to 75% of the sample, formed the composition of the Non-atrial etiology group.</p>
			<p>A comparison of echocardiographic measurements between patients with MI of atrial and Non-atrial etiology revealed increased diameters of the intercommissural mitral annulus and its value indexed through the body surface, with larger diameters in the atrial group (<xref ref-type="table" rid="t1">Table 1</xref>).</p>
			<p>The mean intercommissural mitral diameter in the Non-atrial group was 35.067 mm, while in the Atrial group, this value corresponded to 37.071 mm (<italic>p</italic> = 0.012; Cohen's d: 0,580).</p>
			<p>Regarding the indexed values, the mean mitral annulus diameter indexed by the body surface area in the Non-atrial group was 19.36 mm/m², while in the Atrial group, this was 21.63 mm/m² (<italic>p</italic> &lt; 0.001; Cohen's d: 0.972) (<xref ref-type="table" rid="t2">Table 2</xref>).</p>
			<table-wrap id="t2">
				<label>Table 2</label>
				<caption>
					<title>Echocardiographic Data</title>
				</caption>
				<table frame="hsides" rules="groups">
					<colgroup width="25%">
						<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"/>
							<th align="center" valign="middle">Atrial group (N=28)</th>
							<th align="center" valign="middle">Non-atrial group (N=84)</th>
							<th align="center" valign="middle">p-value</th>
						</tr>
					</thead>
					<tbody style="border-bottom: thin solid; border-color: #000000">
						<tr>
							<td align="left" valign="middle">Linear Measurement of Commissural Mitral Annulus (mm)</td>
							<td align="center" valign="middle">37.07 (32-40)</td>
							<td align="center" valign="middle">35.06 (25-43)</td>
							<td align="center" valign="middle">0.012</td>
						</tr>
						<tr style="background-color:#E8CCBF;">
							<td align="left" valign="middle">Indexed Mitral Annulus (mm/m²)</td>
							<td align="center" valign="middle">21.63 ± 1.86</td>
							<td align="center" valign="middle">19.36 ± 2.48</td>
							<td align="center" valign="middle">&lt; 0.001</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Linear Measurement of Left Atrium (mm)</td>
							<td align="center" valign="middle">46 (44-49)</td>
							<td align="center" valign="middle">44 (41-49)</td>
							<td align="center" valign="middle">0.732</td>
						</tr>
						<tr style="background-color:#E8CCBF;">
							<td align="left" valign="middle">Indexed Left Atrial Volume (ml/m²)</td>
							<td align="center" valign="middle">59.02 (57-61)</td>
							<td align="center" valign="middle">38.00 (35-41)</td>
							<td align="center" valign="middle">0.080</td>
						</tr>
						<tr>
							<td align="left" valign="middle">LVEF</td>
							<td align="center" valign="middle">61 (58-64)</td>
							<td align="center" valign="middle">42 (30-54)</td>
							<td align="center" valign="middle">&lt; 0.001</td>
						</tr>
						<tr style="background-color:#E8CCBF;">
							<td align="left" valign="middle">E/e’ ratio</td>
							<td align="center" valign="middle">12 (10-14)</td>
							<td align="center" valign="middle">10 (08-12)</td>
							<td align="center" valign="middle">0.315</td>
						</tr>
					</tbody>
				</table>
				<table-wrap-foot>
					<fn id="TFN2">
						<p>LA: Left Atrium; LVEF: Left Ventricular Ejection Fraction; Kg: Kilograms; m: Meters; HR: Heart Rate; bpm: Beats per Minute.</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
			<p>The diagnostic accuracy of the mitral annulus intercommissural diameter showed an area under the curve (AUC) of 0.659 (95% CI: 0.550 - 0.768), while the ROC curve analysis of the mitral diameter indexed through the body surface exhibited an AUC of 0.767 (95% CI: 0.675 - 0.859). The complementary analysis of the ROC curve identified an optimal cutoff value of 20.8750, at which the sensitivity and specificity were 67.9% (<xref ref-type="fig" rid="f2">Graph 1</xref>).</p>
			<fig id="f2">
				<label>Graph 1</label>
				<caption>
					<title>ROC Curves for evaluating atrial etiology. (A) Non-indexed mitral annulus: AUC = 0.66 (95% CI: 0.550–0.768), indicating moderate discriminatory ability. (B) Mitral annulus indexed by body surface area: AUC = 0.77 (95% CI: 0.675–0.859), suggesting higher diagnostic accuracy. The reference line represents the absence of discriminatory power (AUC = 0.5). The curves were adjusted based on the dimensions of the mitral annulus (intercommissural length or indexed value) and reflect the population heterogeneity, highlighting the superiority of the adjusted index in distinguishing atrial etiology. AUC: area under the curve; ROC: receiver operating characteristic.</title>
				</caption>
				<graphic xlink:href="2675-312X-abcimg-38-01-e20240134-gf02.tif"/>
			</fig>
			<p>These findings highlight the relevance of the indexed intercommissural diameter as a potentially superior diagnostic metric to distinguish Atrial from Non-atrial etiologies of MR (Central Illustration).</p>
		</sec>
		<sec sec-type="discussion">
			<title>Discussion</title>
			<p>The prevalence of FMR in our study (25%) is consistent with the average number reported in previous observational studies, reflecting the relevance of this condition.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B17">17</xref></sup> Moreover, the analysis demonstrated that AF is a relevant marker for atrial etiology, with statistically significant differences between the Atrial and Non-atrial groups (<italic>p</italic> &lt; 0.001). AF prevalence reached 71.4% in the atrial MR group, underscoring its strong association with this etiology.<sup><xref ref-type="bibr" rid="B18">18</xref>-<xref ref-type="bibr" rid="B20">20</xref></sup> These findings reinforce the importance of considering AF when identifying the atrial functional etiology in patients with MR.</p>
			<p>In this study, a statistically significant difference was observed in the median ages between groups. Patients in the Atrial group had a higher median age (77 years; interquartile range: 73–84) compared to the Non-atrial group (67 years; interquartile range: 60–71; <italic>p</italic> &lt; 0.001). This pattern is in agreement with data previously reported in the literature, which associates advanced age with a greater predisposition to the atrial etiology of MR.<sup><xref ref-type="bibr" rid="B18">18</xref>,<xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B22">22</xref></sup> Aging is associated with structural changes such as Left Atrial dilation, which contribute to the development of FMR. These findings reinforce the relevance of age as a relevant pathophysiological factor in determining the etiology of MR.</p>
			<p>In the Atrial etiology group, the gender distribution showed 42.9% males and 57.1% females, indicating a slight female predominance. In the Non-atrial group, the proportion of men was considerably higher, representing 67.9% of the participants (55 of 81 individuals). The difference in gender distribution between the groups was statistically significant (<italic>p</italic> = 0.019), suggesting that gender may influence the etiology of MR. Although the exact mechanisms remain unclear, previous studies suggest anatomical and hormonal factors may contribute to atrial remodeling and the atrial etiology of MR development.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> However, these hypotheses still require further investigation.</p>
			<p>In the Atrial group, LVEF showed a mean of 56.04 ± 7.53%, while in the Non-atrial group, the mean was significantly lower, reaching 44.42 ± 1.90% (<italic>p</italic> &lt; 0.001). The preservation of the ejection fraction in the atrial group reflects a striking characteristic of this group, since the reduction in LVEF, when present, occurs only in advanced stages of atrial FMR.<sup><xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B23">23</xref>-<xref ref-type="bibr" rid="B25">25</xref></sup> FMR is recognized as an important prognostic indicator in patients with AF and HFpEF. This condition is associated with a higher risk of progressive systolic dysfunction and reduced LVEF, factors that contribute to clinical worsening and adverse outcomes.<sup><xref ref-type="bibr" rid="B26">26</xref></sup> These findings reinforce the need for careful monitoring of left ventricular function in this clinical context.</p>
			<p>The behavior of the mitral annulus and the mitral annulus indexed by body surface area was of particular interest in this study. Prior research on the mitral annulus as a diagnostic tool for FMR has yielded conflicting results, with most studies relying on absolute measurements obtained via transthoracic echocardiography.<sup><xref ref-type="bibr" rid="B27">27</xref></sup> This study utilized transesophageal echocardiography due to its superior precision in assessing the mitral valve, annular complex, and valve morphology.<sup><xref ref-type="bibr" rid="B27">27</xref>-<xref ref-type="bibr" rid="B29">29</xref></sup> Body surface area indexing was used to ensure greater reliability of measurements, especially in heterogeneous populations. This approach allows for a more standardized assessment adjusted to the individuality of patients, expanding its clinical applicability.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> These factors reinforce the importance of indexing in the context of FMR, where diagnostic accuracy is essential.</p>
			<p>The intercommissural mitral annular diameter was compared between atrial and non-atrial MR groups, revealing significant differences in both absolute and indexed measurements. The mean absolute diameter was 35 mm in the Non-atrial group and 37.1 mm in the Atrial group (<italic>p</italic> = 0.012), with a Cohen's d of 0.580, indicating a moderate effect size. When adjusted for body surface area, the difference became even more pronounced, with mean values of 19.35 mm/m² in the non-atrial group and 21.63 mm/m² in the atrial group (<italic>p</italic> &lt; 0.001, Cohen's d = 0.972), indicating a large effect size.</p>
			<p>These findings confirm that indexing by body surface area enhances the detection of mitral annular changes, standardizing measurements to account for individual patient characteristics. This approach is particularly useful in heterogeneous populations and may improve clinical decision-making by refining the differentiation between atrial and non-atrial MR.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup></p>
			<p>The analysis of diagnostic accuracy using the ROC curve for the intercommissural diameter of the mitral annulus revealed an AUC of 0.659 (95% CI: 0.550–0.768), indicating only moderate accuracy in distinguishing between the atrial and non-atrial groups. On the other hand, indexing the mitral diameter by body surface area showed superior relevance, with an AUC of 0.767 (95% CI: 0.675–0.859), reflecting a more robust diagnostic discrimination capacity.</p>
			<p>Additionally, the ROC curve analysis identified an optimal cutoff value of 20.8750 mm/m², with sensitivity and specificity of 67.9%. These findings reinforce the potential of indexed diameter as a superior tool when compared to the absolute value of the valve annulus in diagnostic algorithms, offering greater accuracy in differentiating between atrial and non-atrial etiologies of MR.</p>
			<p>While indexing the mitral annular diameter increased diagnostic accuracy compared to absolute measurements, limitations remain. The C statistic and Youden index analysis suggest that, when used in isolation, the indexed annular diameter provides only modest diagnostic accuracy. This underscores the need for more comprehensive diagnostic models that integrate indexed diameter with additional clinical and echocardiographic variables to improve atrial MR identification.</p>
		</sec>
		<sec sec-type="conclusions">
			<title>Conclusion</title>
			<p>The findings support the use of indexed diameter as a superior metric over absolute annular size in diagnostic algorithms, offering greater accuracy in differentiating MR etiologies. However, incorporating this measure into broader diagnostic frameworks may further enhance its clinical utility.</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 article is part of the thesis of Doctoral submitted by Alexandre Costa Souza, from Instituto Dor de ensino e pesquisa (Idor).</p>
			</fn>
			<fn fn-type="other" id="fn3">
				<label>Ethics Approval and Consent to Participate</label>
				<p>This study was approved by the Ethics Committee of the Hospital São Rafael under the protocol number 5722007. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
			</fn>
		</fn-group>
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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.20240134</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Artigo Original</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Desempenho do Diâmetro do Anel Mitral no Diagnóstico da Etiologia Atrial na Insuficiência Mitral: Uma Análise Comparativa</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0003-0842-8223</contrib-id>
					<name>
						<surname>Souza</surname>
						<given-names>Alexandre Costa</given-names>
					</name>
					<role>Concepção e desenho da pesquisa</role>
					<role>obtenção de dados</role>
					<role>análise e interpretação dos dados e análise estatística</role>
					<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
					<xref ref-type="corresp" rid="c2"/>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-1375-785X</contrib-id>
					<name>
						<surname>Junqueira</surname>
						<given-names>Bruna de Mattos Ivo</given-names>
					</name>
					<role>Concepção e desenho da pesquisa</role>
					<role>redação do manuscrito</role>
					<role>revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-3275-9762</contrib-id>
					<name>
						<surname>Drubi</surname>
						<given-names>Stephanie de Azevedo</given-names>
					</name>
					<role>obtenção de dados</role>
					<role>redação do manuscrito</role>
					<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-3676-5502</contrib-id>
					<name>
						<surname>Gomes</surname>
						<given-names>Laila Caroline</given-names>
					</name>
					<role>redação do manuscrito</role>
					<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0003-2425-4569</contrib-id>
					<name>
						<surname>Freire</surname>
						<given-names>Marcus Vinicius</given-names>
					</name>
					<role>revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0007-3613-5790</contrib-id>
					<name>
						<surname>Pinheiro</surname>
						<given-names>Priscila</given-names>
					</name>
					<role>obtenção de dados</role>
					<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-7440-6930</contrib-id>
					<name>
						<surname>Basile</surname>
						<given-names>Alessandra Ghattas</given-names>
					</name>
					<role>obtenção de dados</role>
					<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-0656-8399</contrib-id>
					<name>
						<surname>Sales</surname>
						<given-names>Marco André Moraes</given-names>
					</name>
					<role>redação do manuscrito</role>
					<role>revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-1465-2339</contrib-id>
					<name>
						<surname>Guedes</surname>
						<given-names>Ricardo André Sales Pereira</given-names>
					</name>
					<role>redação do manuscrito</role>
					<role>revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-5129-7639</contrib-id>
					<name>
						<surname>Macêdo</surname>
						<given-names>Carolina Thé</given-names>
					</name>
					<role>revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
				</contrib>
				<aff id="aff3">
					<label>1</label>
					<addr-line>
						<named-content content-type="city">Salvador</named-content>
						<named-content content-type="state">BA</named-content>
					</addr-line>
					<country country="BR">Brasil</country>
					<institution content-type="original">Hospital São Rafael/ Rede D’Or, Salvador, BA – Brasil</institution>
				</aff>
				<aff id="aff4">
					<label>2</label>
					<addr-line>
						<named-content content-type="city">Salvador</named-content>
						<named-content content-type="state">BA</named-content>
					</addr-line>
					<country country="BR">Brasil</country>
					<institution content-type="original">Instituto D’Or de ensino e pesquisa, Idor, Salvador, BA – Brasil</institution>
				</aff>
			</contrib-group>
			<author-notes>
				<corresp id="c2">
					<label>Correspondência:</label><bold>Alexandre Costa Souza</bold> • Hospital São Rafael. Avenida São Rafael. CEP: <postal-code>41253-190</postal-code>. Salvador, BA – Brasil E-mail: <email>alexandrecostahsr@gmail.com</email>
				</corresp>
				<fn fn-type="conflict">
					<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 Insuficiência Mitral Funcional Atrial (IMFA) caracteriza-se pela dilatação do anel mitral e alterações funcionais sem comprometimento estrutural dos folhetos ou do aparato subvalvar. A IMFA está associada a maior mortalidade cardiovascular, entretanto é frequentemente caracterizada como um diagnóstico de exclusão devido à ausência de critérios diagnósticos mais precisos. Portanto, destaca-se a necessidade de identificar marcadores que a diferenciam de outros tipos de Insuficiência Mitral (IM).</p>
				</sec>
				<sec>
					<title>Objetivo:</title>
					<p>Determinar a acurácia do diâmetro intercomissural do anel mitral e de seu valor indexado pela superfície corpórea, na discriminação diagnóstica da etiologia atrial em pacientes com IM.</p>
				</sec>
				<sec>
					<title>Métodos:</title>
					<p>Trata-se de estudo observacional de corte transversal com 109 pacientes diagnosticados com IM de grau moderado ou grave. Os dados foram obtidos no período entre outubro de 2022 a janeiro de 2024, a partir de ecocardiogramas transesofágicos realizados em um hospital de referência na cidade de Salvador/BA.</p>
				</sec>
				<sec>
					<title>Resultados:</title>
					<p>A média etária foi de 69 ± 15, sendo 67 masculinos e 28 casos de etiologia atrial. A comparação entre pacientes com IM de etiologia Atrial frente aos Não Atriais revelou um aumento significativo dos diâmetros do anel mitral intercomissural e do seu valor indexado, com diâmetros consideravelmente maiores no grupo Atrial (p = 0,009; IC 95%: 0,501 a 3,507). A análise da curva <italic>Receiver Operating Characteristic</italic> (ROC) identificou um valor de corte ótimo de 20,8750, com sensibilidade e especificidade de 67,9%.</p>
				</sec>
				<sec>
					<title>Conclusão:</title>
					<p>A indexação do diâmetro do anel mitral pela superfície corporal melhora a acurácia diagnóstica na identificação da etiologia atrial da IM em comparação ao diâmetro isolado, sugerindo seu potencial benefício quando incorporada a algoritmos diagnósticos mais abrangentes.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="pt">
				<title>Palavras-chave:</title>
				<kwd>Insuficiência da Valva Mitral</kwd>
				<kwd>Insuficiência Cardíaca</kwd>
				<kwd>Fibrilação Atrial</kwd>
			</kwd-group>
		</front-stub>
		<body>
			<fig id="f3">
				<caption>
					<title>AUC: área sob a curva; IMFA: Insuficiência Mitral Funcional Atrial.</title>
				</caption>
				<graphic xlink:href="2675-312X-abcimg-38-01-e20240134-pt-gf01.tif"/>
			</fig>
			<sec sec-type="intro">
				<title>Introdução</title>
				<p>A Insuficiência Mitral (IM) é uma das valvopatias mais prevalentes no mundo, com avanços contínuos na compreensão de sua fisiopatologia, diagnóstico e manejo.<sup><xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B4">4</xref></sup> Entre suas apresentações etiológicas, a Insuficiência Mitral Funcional Atrial (IMFA) destaca-se por sua relevância clínica, especialmente no contexto da Fibrilação Atrial (FA) e da Insuficiência Cardíaca com Fração de Ejeção Preservada (ICFEP).<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> Essa condição é caracterizada pela dilatação do anel mitral e alterações funcionais da válvula sem comprometimento estrutural dos folhetos ou do aparato subvalvar. A avaliação detalhada do átrio esquerdo e do anel mitral é crucial para seu diagnóstico.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> O aumento da prevalência de FA e ICFEP ressalta a importância de estratégias diagnósticas e terapêuticas mais acuradas para a IMFA.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> Essa condição está associada a maior mortalidade, e intervenções como o controle de ritmo têm demonstrado potencial para reduzir sua frequência.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
				<p>A FA é uma condição comum associada à IMFA, mas estudos indicam que a disfunção diastólica do ventrículo esquerdo também desempenha um papel no remodelamento atrial, contribuindo para o desenvolvimento dessa valvopatia.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup> Os mecanismos fisiopatológicos incluem alterações anatômicas e funcionais significativas. O fenômeno conhecido como <italic>‘hamstringing’</italic>, caracterizado pela restrição do movimento do folheto mitral posterior, e o ‘<italic>bending</italic>’, deformação patológica do folheto sob tensão hemodinâmica, comprometem diretamente a funcionalidade valvar. Além disso, mudanças na razão entre a área dos folhetos e do anel mitral, associadas ao <italic>tethering</italic> atrial causado pelo deslocamento posterior do anel em resposta ao aumento do átrio esquerdo, contribuem para a deficiência de coaptação mitral. Essas alterações mostram que a IMFA resulta de um remodelamento valvar e atrial combinado, não se restringindo apenas às dimensões anulares. Esses processos impactam diretamente na coaptação valvar e agravam a severidade da IM.<sup><xref ref-type="bibr" rid="B10">10</xref>-<xref ref-type="bibr" rid="B12">12</xref></sup></p>
				<p>Embora existam amplas discussões na literatura sobre a fisiopatologia da IM e seus achados clínicos e ecocardiográficos, há uma carência de estudos voltados ao desenvolvimento de critérios diagnósticos aprimorados para essa condição específica.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Diante disso, o presente estudo teve como objetivo geral determinar a acurácia do diâmetro intercomissural do anel mitral e de seu valor indexado pela superfície corpórea, através da ecocardiografia transesofágica, na discriminação diagnóstica da etiologia atrial em pacientes com IM.</p>
			</sec>
			<sec sec-type="methods">
				<title>Metodologia</title>
				<p>Trata-se de um estudo observacional de corte transversal, realizado com 109 pacientes diagnosticados com IM de grau moderado ou grave. As imagens ecocardiográficas foram obtidas por ecocardiograma transesofágico em um hospital de referência localizado em Salvador/BA, entre outubro de 2022 e janeiro de 2024.</p>
				<sec>
					<title>Pacientes</title>
					<p>A seleção dos pacientes constituiu uma amostra de conveniência, fundamentada na indicação clínica do ecocardiograma transesofágico pelos cardiologistas assistentes responsáveis pelo acompanhamento. Essa indicação baseou-se em critérios clínicos, considerando a necessidade de uma avaliação detalhada da valva mitral e da gravidade da insuficiência para o planejamento terapêutico. Foram incluídos todos os pacientes com IM moderada ou grave ao estudo complementar transesofágico realizados entre outubro de 2022 e janeiro de 2024, em regime ambulatorial ou hospitalar. O critério de exclusão foi a presença de IM apenas discreta ao método transesofágico ou a presença de dispositivo protético na valva mitral.</p>
					<p>A amostra foi composta por dois grupos: pacientes com IM de etiologia atrial (N = 25) e de etiologia não atrial (N = 84). Entre os grupos, observaram-se diferenças significativas nas características clínicas e ecocardiográficas. O grupo Atrial apresentou idade mediana superior (77 anos, IC 95%: 73-84) em relação ao grupo Não Atrial (67 anos, IC 95%: 60-71; <italic>p</italic> &lt; 0,001), além de maior prevalência de fibrilação atrial (FA) (72% vs. 34%; <italic>p</italic> &lt; 0,001). Já o grupo não atrial mostrou maior proporção de pacientes do sexo masculino (68% vs. 42%; <italic>p</italic> = 0,019).</p>
					<p>Do ponto de vista ecocardiográfico, os pacientes do grupo Atrial apresentaram diâmetros maiores no anel mitral, tanto na medida linear (46,04 mm vs. 44,37 mm; <italic>p</italic> = 0,012) quanto no índice ajustado pela superfície corpórea (21,63 ± 1,86 vs. 19,36 ± 2,48; <italic>p</italic> &lt; 0,001). Além disso, o volume do átrio esquerdo foi significativamente maior no grupo atrial (59,02 ml/m² vs. 38,00 ml/m²; <italic>p</italic> = 0,08). Outras características, como fração de ejeção do ventrículo esquerdo (FEVE) e a relação E/e’, não apresentaram diferenças significativas entre os grupos (<italic>p</italic> &gt; 0,05).</p>
				</sec>
				<sec>
					<title>Ecocardiograma</title>
					<p>A escolha do ecocardiograma transesofágico para avaliação da IM deu-se pela sua superioridade na avaliação do estudo anatômico e funcional da valva mitral.<sup><xref ref-type="bibr" rid="B13">13</xref>-<xref ref-type="bibr" rid="B15">15</xref></sup> As imagens ecocardiográficas foram obtidas seguindo protocolo padronizado com equipamento de alta resolução (GE <italic>Healthcare</italic>, E95).</p>
					<p>A dimensão do anel mitral intercomissural foi avaliada em seu diâmetro, através de dimensão linear do corte intercomissural, obtido em corte de esôfago médio a 60º. Além disso, dois avaliadores experientes realizaram uma classificação concordante da IM em dois grupos, baseando-se em sua etiologia: atrial e não-atrial, conforme diretrizes vigentes e em casos de discordância um terceiro avaliador foi recrutado.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
					<p>O diagnóstico de IMFA ocorreu baseado nos seguintes critérios: anel valvar mitral dilatado ao exame transtorácico em caráter dicotômico (&gt; 35mm na sístole no corte paraesternal longitudinal ao exame transtorácico), ausência de doença valvar mitral de etiologia primária, dilatação significativa do átrio esquerdo (volume indexado: &gt; 42ml/m²) e ausência de disfunção ventricular significativa (FEVE: &gt; 45%, avaliado através do método de Simpson).<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B16">16</xref></sup> Esses critérios foram aplicados para diferenciar os casos de IMFA e orientar a análise do desempenho do diâmetro intercomissural como marcador diagnóstico.</p>
				</sec>
				<sec>
					<title>Análise estatística</title>
					<p>A análise estatística foi realizada utilizando o software IBM SPSS Statistics para Windows, versão 27.0 (IBM corp, Armonk, NY, EUA). Na análise descritiva, as variáveis categóricas foram apresentadas como frequências e porcentagens, enquanto as variáveis contínuas foram descritas por média e desvio padrão. A normalidade das variáveis contínuas foi avaliada pelo teste de Shapiro-Wilk, adotando-se como critério para normalidade um valor de <italic>p</italic> &gt; 0,05.</p>
					<p>As comparações entre os grupos Atrial e Não Atrial seguiram diferentes abordagens conforme a natureza das variáveis. Para as variáveis categóricas, aplicou-se o teste de qui-quadrado de Pearson. As variáveis contínuas com distribuição normal foram analisadas pelo teste t de Student para amostras independentes, com o tamanho do efeito das diferenças significativas sendo quantificado pelo d de Cohen. Em casos de distribuição não normal, utilizou-se o teste <italic>U</italic> de Mann-Whitney para comparação entre os grupos. Para todos os testes, adotou-se um nível de confiança de 95%.</p>
					<p>Além disso, a análise da curva ROC foi realizada para avaliar a capacidade diagnóstica do diâmetro do anel mitral e do anel mitral indexado pela superfície corporal na distinção entre etiologias Atrial e Não Atrial da IM. A estatística C foi utilizada como medida quantitativa de acurácia, sendo valores acima de 0,7 considerados indicativos de boa capacidade discriminatória. Para identificar o ponto de corte ótimo, aplicou-se o índice de Youden, determinando o valor que melhor discrimina a etiologia funcional atrial da IM com base no anel mitral indexado.</p>
				</sec>
			</sec>
			<sec sec-type="results">
				<title>Resultados</title>
				<p>No presente estudo, um total de 109 pacientes foram avaliados com idade média de 69 ± 15 anos. A maioria dos pacientes incluídos na amostra eram do sexo masculino, com o total de 67 homens participantes, correspondendo assim a 61,4% da população. Na amostra analisada, 44% dos pacientes apresentavam diagnóstico conhecido de FA, sendo 20 pacientes no grupo atrial e 28 no grupo não atrial. A presença de FA teve diferença estatisticamente significativa entre os grupos (<italic>p</italic> &lt; 0,001) (<xref ref-type="table" rid="t3">Tabela 1</xref>).</p>
				<table-wrap id="t3">
					<label>Tabela 1</label>
					<caption>
						<title>Dados demográficos e clínicos</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup width="25%">
							<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"/>
								<th align="center" valign="middle">Grupo Atrial (N=28)</th>
								<th align="center" valign="middle">Grupo não-Atrial (N=84)</th>
								<th align="center" valign="middle">p valor</th>
							</tr>
						</thead>
						<tbody style="border-bottom: thin solid; border-color: #000000">
							<tr>
								<td align="left" valign="middle">Idade - anos</td>
								<td align="center" valign="middle">77 (73-84)</td>
								<td align="center" valign="middle">67 (60-71)</td>
								<td align="center" valign="middle">&lt; 0,001</td>
							</tr>
							<tr style="background-color:#E8CCBF;">
								<td align="left" valign="middle">Gênero Masculino - nº (%)</td>
								<td align="center" valign="middle">12 (48%)</td>
								<td align="center" valign="middle">55 (65%)</td>
								<td align="center" valign="middle">0,19</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Fibrilação Atrial - nº (%)</td>
								<td align="center" valign="middle">20 (72%)</td>
								<td align="center" valign="middle">28 (33%)</td>
								<td align="center" valign="middle">&lt; 0,001</td>
							</tr>
							<tr style="background-color:#E8CCBF;">
								<td align="left" valign="middle">Dislipidemia - nº (%)</td>
								<td align="center" valign="middle">21 (75%)</td>
								<td align="center" valign="middle">42 (50%)</td>
								<td align="center" valign="middle">0,025</td>
							</tr>
							<tr>
								<td align="left" valign="middle">AVCI - nº (%)</td>
								<td align="center" valign="middle">05 (18%)</td>
								<td align="center" valign="middle">13 (16%)</td>
								<td align="center" valign="middle">0,805</td>
							</tr>
							<tr style="background-color:#E8CCBF;">
								<td align="left" valign="middle">Doença Arterial Coronariana prévia - nº (%)</td>
								<td align="center" valign="middle">07 (25%)</td>
								<td align="center" valign="middle">34 (40%)</td>
								<td align="center" valign="middle">0,141</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Diabetes Mellitus - nº (%)</td>
								<td align="center" valign="middle">07 (25%)</td>
								<td align="center" valign="middle">31 (37%)</td>
								<td align="center" valign="middle">0,204</td>
							</tr>
							<tr style="background-color:#E8CCBF;">
								<td align="left" valign="middle">Hipertensão Arterial Sistêmica - nº (%)</td>
								<td align="center" valign="middle">22 (78%)</td>
								<td align="center" valign="middle">48 (57%)</td>
								<td align="center" valign="middle">0,066</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Insuficiência Renal Crônica - nº (%)</td>
								<td align="center" valign="middle">05 (18%)</td>
								<td align="center" valign="middle">14 (17%)</td>
								<td align="center" valign="middle">0,976</td>
							</tr>
							<tr style="background-color:#E8CCBF;">
								<td align="left" valign="middle">Peso Kg - nº (%)</td>
								<td align="center" valign="middle">72,04 (70-74)</td>
								<td align="center" valign="middle">73,51 (72-75)</td>
								<td align="center" valign="middle">0,632</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN3">
							<p>AVCi: Acidente vascular cerebral isquêmico.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
				<p>Os pacientes foram divididos em dois grupos conforme a etiologia da IM, sendo 28 pacientes alocados no grupo etiologia funcional atrial, correspondendo assim a 25% da população. Os demais participantes, correspondente a 75% da amostra, formaram a composição do grupo de etiologia não atrial.</p>
				<p>A comparação das medidas ecocardiográficas entre pacientes com IM de etiologia funcional atrial frente ao grupo não atrial, revelou um aumento dos diâmetros do anel mitral intercomissural e do seu valor indexado através da superfície corporal, com diâmetros maiores no grupo atrial (<xref ref-type="table" rid="t3">Tabela 1</xref>).</p>
				<p>A média do diâmetro mitral intercomissural no grupo Não Atrial foi de 35,067 mm, enquanto no grupo Atrial esse valor correspondeu a 37,071 mm (<italic>p</italic> = 0,012; d de Cohen: 0,580).</p>
				<p>Em relação aos valores indexados, a média do diâmetro do anel mitral indexado pela área de superfície corpórea no grupo Não Atrial foi de 19,36 mm/m², enquanto que, no grupo Atrial, esse valor foi de 21,63 mm/m² (<italic>p</italic> &lt; 0.001; d de Cohen: 0,972) (<xref ref-type="table" rid="t4">Tabela 2</xref>).</p>
				<table-wrap id="t4">
					<label>Tabela 2</label>
					<caption>
						<title>Dados Ecocardiográficos</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup width="25%">
							<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"/>
								<th align="center" valign="middle">Grupo Atrial (N = 28)</th>
								<th align="center" valign="middle">Grupo não-Atrial (N = 84)</th>
								<th align="center" valign="middle">p valor</th>
							</tr>
						</thead>
						<tbody style="border-bottom: thin solid; border-color: #000000">
							<tr>
								<td align="left" valign="middle">Medida Linear do Anel Mitral Comissural (mm)</td>
								<td align="center" valign="middle">37,07 (32-40)</td>
								<td align="center" valign="middle">35,06 (25-43)</td>
								<td align="center" valign="middle">0,012</td>
							</tr>
							<tr style="background-color:#E8CCBF;">
								<td align="left" valign="middle">Anel Mitral Indexado (mm/m²)</td>
								<td align="center" valign="middle">21,63 ± 1,86</td>
								<td align="center" valign="middle">19,36 ± 2,48</td>
								<td align="center" valign="middle">&lt; 0,001</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Medida linear do Átrio Esquerdo (mm)</td>
								<td align="center" valign="middle">46 (44-49)</td>
								<td align="center" valign="middle">44 (41-49)</td>
								<td align="center" valign="middle">0,732</td>
							</tr>
							<tr style="background-color:#E8CCBF;">
								<td align="left" valign="middle">Volume Indexado do Átrio Esquerdo (ml/m²)</td>
								<td align="center" valign="middle">59,02 (57-61)</td>
								<td align="center" valign="middle">38,00 (35-41)</td>
								<td align="center" valign="middle">0,080</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Fração de Ejeção do Ventrículo Esquerdo</td>
								<td align="center" valign="middle">61 (58-64)</td>
								<td align="center" valign="middle">42 (30-54)</td>
								<td align="center" valign="middle">&lt; 0,001</td>
							</tr>
							<tr style="background-color:#E8CCBF;">
								<td align="left" valign="middle">E/e’</td>
								<td align="center" valign="middle">12 (10-14)</td>
								<td align="center" valign="middle">10 (08-12)</td>
								<td align="center" valign="middle">0,315</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN4">
							<p>AE: átrio esquerdo; FEVE: fração de ejeção do ventrículo esquerdo; Kg: quilogramas; m: metros; FC: frequência cardíaca; bpm: batimentos por minuto.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
				<p>A acurácia diagnóstica do diâmetro intercomissural do anel mitral obteve uma área sob a curva (AUC) de 0,659 (IC 95%: 0,550 - 0,768), enquanto a análise da curva ROC do diâmetro mitral indexado através da superfície corporal exibiu uma AUC de 0,767 (IC 95%: 0,675 - 0,859). A análise complementar da curva ROC identificou um valor de corte ótimo de 20,8750, no qual a sensibilidade e especificidade foi de 67,9% (<xref ref-type="fig" rid="f4">gráfico 1</xref>).</p>
				<fig id="f4">
					<label>Gráfico 1</label>
					<caption>
						<title>Curvas (ROC) para avaliação da etiologia atrial. (A) Anel mitral não indexado: AUC = 0,66 (IC 95%: 0,550–0,768), indicando capacidade discriminatória moderada. (B) Anel mitral indexado pela superfície corporal: AUC = 0,77 (IC 95%: 0,675–0,859), sugerindo maior acurácia diagnóstica. A linha de referência representa ausência de poder discriminatório (AUC = 0,5). As curvas foram ajustadas com base nas dimensões do anel mitral (comprimento intercomissural ou valor indexado) e refletem a heterogeneidade populacional, destacando a superioridade do índice ajustado na distinção da etiologia atrial. AUC: área sob a curva; ROC: Receiver Operating Characteristic.</title>
					</caption>
					<graphic xlink:href="2675-312X-abcimg-38-01-e20240134-pt-gf02.tif"/>
				</fig>
				<p>Esses achados reforçam a relevância do diâmetro intercomissural indexado como uma métrica diagnóstica potencialmente superior para distinguir etiologias Atrial e Não Atrial da IM (Figura Central).</p>
			</sec>
			<sec sec-type="discussion">
				<title>Discussão</title>
				<p>A prevalência de IMFA em nosso estudo, observada em 25% dos indivíduos da amostra, é consistente com a média relatada em estudos observacionais prévios, refletindo a relevância desta condição.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B17">17</xref></sup> Além disso, a análise demonstrou que a FA é um marcador relevante para a etiologia atrial, com diferenças estatisticamente significativas entre os grupos Atrial e Não Atrial (<italic>p</italic> &lt; 0,001). A prevalência de FA alcançou 71,4% no grupo Atrial, destacando sua associação robusta com essa etiologia.<sup><xref ref-type="bibr" rid="B18">18</xref>-<xref ref-type="bibr" rid="B20">20</xref></sup> Esses achados reforçam a importância de considerar a presença de FA na identificação da etiologia funcional atrial em pacientes com IM.</p>
				<p>No presente estudo, foi observada uma diferença estatisticamente significativa nas medianas de idade entre os grupos comparados. Os pacientes do grupo Atrial apresentaram uma mediana de idade superior (77 anos; intervalo interquartil: 73–84) em relação ao grupo Não Atrial (67 anos; intervalo interquartil: 60–71; <italic>p</italic> &lt; 0,001). Este padrão concorda com dados previamente relatados na literatura, que associam idade avançada a uma maior predisposição à etiologia atrial da IM.<sup><xref ref-type="bibr" rid="B18">18</xref>,<xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B22">22</xref></sup> O envelhecimento está associado a alterações estruturais como a dilatação do Átrio Esquerdo, que contribuem para o desenvolvimento da IMFA. Esses achados reforçam a relevância da idade como fator fisiopatológico relevante na determinação da etiologia da IM.</p>
				<p>No grupo de etiologia Atrial, a distribuição por sexo mostrou 42,9% de indivíduos do sexo masculino e 57,1% do sexo feminino, indicando uma leve predominância feminina. Já no grupo Não Atrial, a proporção de homens foi consideravelmente maior, representando 67,9% dos participantes (55 de 81 indivíduos). A diferença na distribuição por sexo entre os grupos foi estatisticamente significativa (<italic>p</italic> = 0,019), sugerindo que o sexo pode influenciar a etiologia da IM. Embora a razão exata para essa associação não esteja completamente elucidada, estudos anteriores aventam fatores como diferenças anatômicas e hormonais que podem impactar o remodelamento atrial e contribuir para a etiologia atrial da IM.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> No entanto, essas hipóteses ainda requerem investigação mais aprofundada para confirmação.</p>
				<p>No grupo Atrial, a FEVE apresentou uma média de 56,04 ± 7,53%, enquanto no grupo Não Atrial, a média foi significativamente menor, situando-se em 44,42 ± 1,90% (<italic>p</italic> &lt; 0,001). A preservação da fração de ejeção no grupo Atrial reflete uma característica marcante desse grupo, pois a redução da FEVE, quando presente, ocorre apenas em fases avançadas da IMFA.<sup><xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B23">23</xref>-<xref ref-type="bibr" rid="B25">25</xref></sup> A IMFA é reconhecida como um indicador prognóstico importante em pacientes com FA e ICFEP. Essa condição está associada a um maior risco de disfunção sistólica progressiva e redução da FEVE, fatores que contribuem para a piora clínica e para desfechos adversos.<sup><xref ref-type="bibr" rid="B26">26</xref></sup> Esses achados reforçam a necessidade de um monitoramento atento da função ventricular esquerda nesse contexto clínico.</p>
				<p>O comportamento do anel mitral e do anel mitral indexado pela superfície corporal foi de particular interesse neste estudo. Trabalhos anteriores mostraram resultados divergentes sobre o valor do anel mitral como ferramenta diagnóstica para a IMFA, com a maioria utilizando valores absolutos obtidos por ecocardiograma transtorácico.<sup><xref ref-type="bibr" rid="B27">27</xref></sup> Neste estudo, optou-se pelo ecocardiograma transesofágico, que oferece maior precisão na avaliação da valva mitral, do complexo valvar e do anel, destacando-se como uma ferramenta superior para esse propósito.<sup><xref ref-type="bibr" rid="B27">27</xref>-<xref ref-type="bibr" rid="B29">29</xref></sup> A indexação pela superfície corporal foi utilizada para garantir maior fidedignidade das medidas, especialmente em populações heterogêneas. Essa abordagem permite uma avaliação mais padronizada e ajustada à individualidade dos pacientes, ampliando sua aplicabilidade clínica.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> Esses fatores reforçam a importância da indexação no contexto da lMFA, onde a precisão diagnóstica é fundamental.</p>
				<p>Nossa investigação comparou o diâmetro do anel mitral intercomissural em grupos de etiologia Atrial e Não Atrial, evidenciando diferenças significativas tanto em medidas absolutas quanto indexadas pela superfície corporal. O diâmetro médio absoluto foi de 35 mm no grupo Não Atrial e 37,1 mm no grupo Atrial (<italic>p</italic> = 0,012), com um d de Cohen de 0,580, indicando um tamanho de efeito moderado. Quando indexado pela área de superfície corporal, essa diferença tornou-se ainda mais pronunciada, com médias de 19,35 mm/m² no grupo Não Atrial e 21,63 mm/m² no grupo Atrial (<italic>p</italic> &lt; 0,001) e um d de Cohen de 0,972, indicando uma grande magnitude de efeito para o valor indexado do anel mitral.</p>
				<p>Esses achados reforçam que a indexação pela superfície corporal não apenas melhora a acurácia na detecção de alterações do anel mitral, mas também ajusta as medidas às características individuais dos pacientes, proporcionando uma avaliação mais padronizada e representativa. Essa abordagem é particularmente útil em populações heterogêneas e pode ter implicações importantes na prática clínica, auxiliando na diferenciação diagnóstica entre etiologias Atrial e Não Atrial da IM.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup></p>
				<p>A análise da acurácia diagnóstica utilizando a curva ROC para o diâmetro intercomissural do anel mitral revelou uma AUC de 0,659 (IC 95%: 0,550–0,768), indicando uma precisão apenas moderada na distinção entre os grupos Atrial e Não Atrial. Por outro lado, a indexação do diâmetro mitral pela superfície corporal apresentou um desempenho superior, com uma AUC de 0,767 (IC 95%: 0,675–0,859), refletindo uma capacidade mais robusta de discriminação diagnóstica.</p>
				<p>Além disso, a análise da curva ROC identificou um valor de corte ótimo de 20,8750 mm/m², com sensibilidade e especificidade de 67,9%. Esses achados reforçam o potencial do diâmetro indexado como uma ferramenta superior quando comparado ao valor absoluto do anel valvar em algoritmos diagnósticos, oferecendo maior precisão na diferenciação entre etiologias Atrial e Não Atrial da IM.</p>
				<p>Embora a indexação do diâmetro do anel mitral pela superfície corporal tenha aumentado a acurácia diagnóstica em comparação ao diâmetro absoluto, a análise de acurácia revela limitações. A estatística C e o valor de corte identificado pelo índice de Youden sugerem que, isoladamente, o anel mitral indexado apresenta acurácia diagnóstica modesta. Esses achados destacam a necessidade de algoritmos diagnósticos mais abrangentes, que integrem o diâmetro indexado a outras variáveis clínicas e ecocardiográficas, para aprimorar a identificação da etiologia atrial da IM.</p>
			</sec>
			<sec sec-type="conclusions">
				<title>Conclusão</title>
				<p>Os achados indicam que a indexação do diâmetro do anel mitral através da superfície corporal melhora a acurácia diagnóstica na identificação da etiologia atrial da IM em comparação ao diâmetro isolado. No entanto, o uso dessa medida de forma integrada a algoritmos diagnósticos mais abrangentes, que considerem variáveis adicionais, pode ampliar ainda mais a precisão diagnóstica.</p>
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				<fn fn-type="financial-disclosure" id="fn4">
					<label>Fontes de Financiamento</label>
					<p>O presente estudo não teve fontes de financiamento externas.</p>
				</fn>
				<fn fn-type="other" id="fn5">
					<label>Vinculação Acadêmica</label>
					<p>Este artigo é parte de tese de Doutorado de Alexandre Costa Souza pela Instituto Dor de ensino e pesquisa (Idor)</p>
				</fn>
				<fn fn-type="other" id="fn6">
					<label>Aprovação Ética e Consentimento Informado</label>
					<p>Este estudo foi aprovado pelo Comitê de Ética do Hospital São Rafael sob o número de protocolo 5722007. Todos os procedimentos envolvidos nesse estudo estão de acordo com a Declaração de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes incluídos no estudo.</p>
				</fn>
			</fn-group>
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	</sub-article>
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