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<article article-type="research-article" dtd-version="1.1" specific-use="sps-1.9" xml:lang="en" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">
	<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.20240089i</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Original Article</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Classifying the Size of an Atrial Septal Defect According to Echocardiographic Parameters and its Association with the Clinical Presentation in Pediatrics</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-0502-7371</contrib-id>
					<name>
						<surname>Ribeiro</surname>
						<given-names>Lívia de Castro</given-names>
					</name>
					<role>acquisition of data</role>
					<role>analysis and interpretation of the data and writing of the manuscript</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-0963-948X</contrib-id>
					<name>
						<surname>Silva</surname>
						<given-names>Rose Mary Ferreira Lisboa da</given-names>
					</name>
					<role>statistical analysis</role>
					<role>critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0003-2481-2647</contrib-id>
					<name>
						<surname>Tonelli</surname>
						<given-names>Henrique de Assis Fonseca</given-names>
					</name>
					<role>Conception and design of the research</role>
					<role>acquisition of data</role>
					<role>critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0001-8288-7116</contrib-id>
					<name>
						<surname>Guimarães</surname>
						<given-names>Adriana Furletti Machado</given-names>
					</name>
					<role>acquisition of data</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-3059-7480</contrib-id>
					<name>
						<surname>Araújo</surname>
						<given-names>Fátima Derlene da Rocha</given-names>
					</name>
					<role>acquisition of data</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0001-5526-7915</contrib-id>
					<name>
						<surname>Meira</surname>
						<given-names>Zilda Maria Alves</given-names>
					</name>
					<role>acquisition of data</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-4610-6439</contrib-id>
					<name>
						<surname>Castilho</surname>
						<given-names>Sandra Regina Tolentino</given-names>
					</name>
					<role>acquisition of data</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Conde</surname>
						<given-names>Alan Alvarez</given-names>
					</name>
					<role>acquisition of data</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0009-4455-6530</contrib-id>
					<name>
						<surname>Valadares</surname>
						<given-names>Lícia Campos</given-names>
					</name>
					<role>acquisition of data</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff1">
				<label>1</label>
				<institution content-type="orgname">Universidade Federal de Minas Gerais</institution>
				<addr-line>
					<named-content content-type="city">Belo Horizonte</named-content>
					<named-content content-type="state">MG</named-content>
				</addr-line>
				<country country="BR">Brazil</country>
				<institution content-type="original">Universidade Federal de Minas Gerais, Belo Horizonte, MG – Brazil</institution>
			</aff>
			<author-notes>
				<corresp id="c01">
					<label>Mailing Address:</label> Livia de Castro Ribeiro • Hospital das Clínicas da Universidade Federal de Minas Gerais. Rua Alfredo Balena, 110. Postal code: 30130-100. Belo Horizonte, MG – Brazil E-mail: <email>liviadecastromed85@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>Karen Saori Shiraishi Sawamur</p>
				</fn>
			</author-notes>
			<pub-date date-type="pub" publication-format="electronic">
				<day>15</day>
				<month>05</month>
				<year>2025</year>
			</pub-date>
			<pub-date date-type="collection" publication-format="electronic">
				<month>04</month>
				<year>2025</year>
			</pub-date>
			<volume>38</volume>
			<issue>2</issue>
			<elocation-id>e20240089</elocation-id>
			<history>
				<date date-type="received">
					<day>17</day>
					<month>09</month>
					<year>2024</year>
				</date>
				<date date-type="rev-recd">
					<day>30</day>
					<month>01</month>
					<year>2025</year>
				</date>
				<date date-type="accepted">
					<day>12</day>
					<month>02</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> Few studies are using linear echocardiographic measurements for classifying the size of Atrial Septal Defect (ASD).</p>
				</sec>
				<sec>
					<title>Objectives</title>
					<p> Investigate the relationship between ASD hemodynamic repercussions and ASD diameter to the mitral annulus diameter (MI/ASD) ratio and ASD diameter to the interatrial septum diameter (ASD/septum) ratio, and describe cutoff points to classify the size of the defect.</p>
				</sec>
				<sec>
					<title>Methods</title>
					<p> An observational, prospective, cross-sectional study, including subjects aged 1 month and 18 years diagnosed with isolated ASD. Hemodynamic repercussion was quantified by clinical evaluation, tricuspid annulus (TA) Z-score, subjective estimation of the enlargement of the right chambers, and the relationship between systemic and pulmonary flows (QP/QS) on echocardiography. Its association with ASD/septum and MI/ASD measurements was also studied. A value of p &lt; 0.05 was considered statistically significant.</p>
				</sec>
				<sec>
					<title>Results</title>
					<p> Thirty-five subjects, mean age 6.3 years, 69% female, mean ASD 13.5 mm. There was a correlation between MI/ASD and the clinical classification of ASD (Pearson: -0.61; p &lt; 0.001), ASD/septum (Pearson: -0.80; p &lt; 0.001), and QP/QS (-0.76; p &lt; 0.001). There was a correlation between ASD/septum and the clinical classification of ASD (Pearson: 0.56; p &lt; 0.001), QP/QS (0.63; p = 0.001), subjective assessment of the right chambers (0.62; p &lt; 0.001), and a weak correlation with the TA Z-score (0.35; p = 0.04). According to the operating characteristic curve for the stable variable classification of ASD according to the subjective right chamber’s size, an area of 0.85 was obtained for ASD/septum (p = 0.001). The cutoff point of 0.27 for large ASD showed sensitivity of 85%, specificity of 86.7%, positive predictive value (PPV) of 86%, negative predictive value (NPV) of 85.2%, and positive likelihood ratio of 6.39.</p>
				</sec>
				<sec>
					<title>Conclusions</title>
					<p> ASD/septum was associated with the hemodynamic repercussion of ASD and was useful in detecting large ASD.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="en">
				<kwd>Atrial Heart Septal Defects</kwd>
				<kwd>Echocardiography</kwd>
				<kwd>Tricuspid Valve</kwd>
				<kwd>Atrial Septum</kwd>
			</kwd-group>
			<counts>
				<fig-count count="6"/>
				<table-count count="12"/>
				<equation-count count="0"/>
				<ref-count count="30"/>
			</counts>
		</article-meta>
	</front>
	<body>
		<p>
					<fig id="f01">
						<label>Central Illustration:</label>
						<caption>
							<title>Classifying the Size of an Atrial Septal Defect According to Echocardiographic Parameters and tts Association with the Clinical Presentation in Pediatrics</title>
							<p>PPV: positive predictive value; ASD: Atrial Septal Defect; NPV: negative predictive value; LR: likelihood ratio; ROC: receiver operating characteristic.</p>
						</caption>
						<graphic xlink:href="2675-312x-abcimg-38-2-e20240089-gf01.tif"/>
					</fig>
				</p>
		<sec sec-type="intro">
			<title>Introduction</title>
			<p>Atrial Septal Defect (ASD) is a congenital structural alteration of the heart in which blood is mixed between the atria through a defect in the Atrial Septum or adjacent structures. Isolated ASD is the third most common cardiac malformation, corresponding to approximately 15% of all congenital heart diseases.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> The prevalence of ASD is twice as high among females compared to males.<xref ref-type="bibr" rid="B2"><sup>2</sup></xref> Transthoracic echocardiographic examination is the most widely used method for diagnosing and evaluating ASD in the pediatric population and is sufficient for adequately defining the lesion and its hemodynamic repercussions in most cases. The linear measurement of the defect, the Atrial Septum Size defect ratio (ASD/septum), the repercussion in the right chambers (signs of volumetric overload), and the measurement of the pulmonary flow/systemic flow (QP/QS) ratio are commonly used to assess the defect size. The ASD/septum measurement has been used informally in clinical practice, with no systematization based on studies and without reliable cutoff points for size classification. The measurement of QP/QS during echocardiography has a major limitation, represented by low reproducibility<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> and difficulty performing.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> The objectives of the study were to investigate, through clinical and echocardiographic assessments, the relationship between ASD hemodynamic repercussion and the measurements of the Mitral Annulus diameter to the ASD diameter (MI/ASD) ratio and the (ASD/septum) ratio, and describe the cutoff points of these ratios that would allow the defect to be classified based on its size.</p>
		</sec>
		<sec sec-type="methods">
			<title>Methods</title>
			<p>This was an observational, prospective, cross-sectional study. The population consisted of 35 subjects with isolated ASD with a single orifice on echocardiographic examination, of both genders, aged between 1 month and 18 years. The study, the Informed Consent Form (ICF), and the Understanding Form (UF) were approved by the Ethics and Research Committee of the university hospital where the research was carried out. The subjects signed the ICF or UF and then underwent echocardiographic examination and clinical evaluation. Those with significant congenital heart disease (excluding patent foramen ovale, mild mitral, tricuspid, and aortic regurgitation, and bicuspid aortic valve without stenosis), cardiomyopathy (primary or secondary), chronic anemia, and pulmonary hypertension not attributed to the presence of ASD were excluded. The convenience sampling method was used.</p>
			<p>The echocardiographic examination was performed with a TOSHIBA device, model APLIO 400, with pediatric and adult transducers with frequencies of 2.5 MHz and 5.0 MHz, respectively, by a pediatric echocardiographer, and the clinical evaluation was performed by a pediatric cardiologist, both members of the team, and blinded to the clinical assessment and vice versa. The clinical assessment was performed on the same day as the echocardiographic evaluation, immediately after it. The degree of repercussion in the right chambers was assessed subjectively, comparing the areas of the Right Atrium (RA) to those of the Left Atrium (LA) and the areas of the Right Ventricle (RV) to those of the Left Ventricle (LV), in a two-dimensional mode, apical four-chamber view,<xref ref-type="bibr" rid="B5"><sup>5</sup></xref> since linear and area measurements of the RA and RV have not been consistently standardized for the pediatric population.<xref ref-type="bibr" rid="B6"><sup>6</sup></xref><sup>-</sup><xref ref-type="bibr" rid="B8"><sup>8</sup></xref> Comparatively, if the right chambers had a smaller, equal, or larger area than the left chambers, the increase was considered absent or mild, moderate, or significant, respectively. Measurements of the interatrial septum and the ASD diameter were performed in two-dimensional mode, in the subcostal section of the Atrial Septum, with the aid of Color Doppler to identify the edges of the defect.<xref ref-type="bibr" rid="B6"><sup>6</sup></xref> To measure the Atrial Septum, the vertical distance between the end of each vena cava was standardized. The ASD was measured in the region with the greatest distance between the edges throughout the cardiac cycle. The ASD/septum ratio was calculated, and this measurement was compared with the hemodynamic repercussion. The magnitude of the shunt through the ASD was estimated by calculating the systemic flow/pulmonary flow (QP/QS) ratio.<xref ref-type="bibr" rid="B6"><sup>6</sup></xref> The diameters of the Mitral and Tricuspid Annuli were measured in two-dimensional mode, in protodiastole. The parasternal longitudinal long axis view of the LV and RV inflow tract were used to measure the anteroposterior diameters (mitral and tricuspid, respectively) and the apical four-chamber view to measure the laterolateral diameters<xref ref-type="bibr" rid="B7"><sup>7</sup></xref> (<xref ref-type="fig" rid="f02">Figure 1</xref>). The diameters were indexed in the form of a Z-score using the Boston reference.<xref ref-type="bibr" rid="B9"><sup>9</sup></xref><sup>-</sup><xref ref-type="bibr" rid="B11"><sup>11</sup></xref> The Tricuspid Annulus (TA) Z-score values were also used to classify the degree of ASD repercussion in the right chambers. The MI/ASD ratio was calculated, and this measurement was compared with the hemodynamic repercussion. ASD size classification by echocardiographic criteria was performed by subjective analysis and Z-score: Small ASD: the right chamber area is smaller than left chamber area and the TA Z-score ranges from +2 to +2.5; medium ASD: the right chamber area is equal to the left chamber area and the TA Z-score ranges from +2.5 to +3; large ASD: the right chamber area is larger than the left chamber area and the TA Z-score is &gt; +3.</p>
			<p>
				<fig id="f02">
					<label>Figure 1</label>
					<caption>
						<title>– Measurement of the interatrial septum, ASD, and mitral and tricuspid annuli on echocardiographic examination. RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle; ASD: Atrial Septal Defect; IVN: inferior vena cava; SVC: superior vena cava; TV: tricuspid valve; MV: mitral valve.</title>
					</caption>
					<graphic xlink:href="2675-312x-abcimg-38-2-e20240089-gf02.tif"/>
				</fig>
			</p>
			<p>The clinical evaluation consisted of an examination of the cardiovascular system guided by criteria that allowed inferences to be made about the size of the ASD.<xref ref-type="bibr" rid="B12"><sup>12</sup></xref> ASD size classification by clinical evaluation was performed according to <xref ref-type="table" rid="t1">Table 1</xref>, and the presence of at least three of the four findings for each column was considered.</p>
			<p>
				<table-wrap id="t1">
					<label>Table 1</label>
					<caption>
						<title>– Classification of ASD size according to clinical criteria</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup>
							<col/>
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead>
							<tr>
								<th align="left" style="font-weight:normal"> </th>
								<th colspan="3" style="font-weight:normal">Size Classification</th>
							</tr>
							<tr>
								<th align="left" style="font-weight:normal">Clinical Parameter</th>
								<th style="font-weight:normal">Small</th>
								<th style="font-weight:normal">Medium</th>
								<th style="font-weight:normal">Large</th>
							</tr>
						</thead>
						<tbody>
							<tr>
								<td>Impulse in BEEI and subxiphoid region</td>
								<td align="center">Absent</td>
								<td align="center">Present</td>
								<td align="center">Present</td>
							</tr>
							<tr>
								<td>Splitting of the second heart sound</td>
								<td align="center">Physiological</td>
								<td align="center">Fixed</td>
								<td align="center">Fixed</td>
							</tr>
							<tr>
								<td>Ejection systolic murmur in the pulmonary area</td>
								<td align="center">Absent or grade I/VI</td>
								<td align="center">Grade II/VI</td>
								<td align="center">Grade &gt; III/VI</td>
							</tr>
							<tr>
								<td>Diastolic murmur in the tricuspid area</td>
								<td align="center">Absent</td>
								<td align="center">Absent</td>
								<td align="center">Present</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN1">
							<p>BEEI: lower left sternal border.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
			</p>
			<p>Statistical analysis: Statistical analysis was performed using Statistical Package for Social Science (SPSS) software version 16.0. The results were expressed as numbers and proportions for categorical variables and as means ± standard deviation for continuous variables. The Shapiro-Wilk test was used to check the normal distribution of variables. Proportions were compared using the Chi-square test or Fisher’s exact test when appropriate. For continuous data, the unpaired Student’s T-test was used for two variables, or the One-Way ANOVA test was used to compare three or more variables. The Pearson coefficient was used to check the correlation between continuous. The correlation based on the coefficient (positive or inverse) was considered very weak (0.00–0.20), weak (0.21–0.40), moderate (0.41–0.60), strong (0.61–0.80), and very strong (0.81–1.00). The operating characteristic curve was applied to evaluate sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), and the positive likelihood ratio of the ASD/septum ratio, considering the size of the septal defect. A P-value of &lt; 0.05 was considered statistically significant.</p>
		</sec>
		<sec sec-type="results">
			<title>Results</title>
			<p>Among the 35 subjects, 24 (69%) were female. The mean age was 6.3 ± 3.9 years, ranging from 0.4 to 17.2 years. The average weight, height, and body surface area were 21.2 kg, 112 cm, and 0.8 m<sup>2</sup>, respectively. Comorbidities were present in 14% of the subjects (n = 5), including asthma (3), genetic syndrome under investigation (1), and neurological and psychomotor development delay in propaedeutics (1).</p>
			<p>Regarding the findings on physical examination, 14 subjects (40%) had fixed splitting of the second heart sound, and 5 (14%) had a diastolic murmur in the tricuspid area. A systolic murmur in the pulmonary area was not detected in six subjects, was grade II in 16 subjects (46%), and grade III ≥ in 13 subjects (37%). RV impulse was not detected in 19 (54%) subjects.</p>
			<p>On echocardiographic examination, all subjects had ostium secundum-type ASD. The data collected are summarized in <xref ref-type="table" rid="t2">Table 2</xref>.</p>
			<p>
				<table-wrap id="t2">
					<label>Table 2</label>
					<caption>
						<title>– Measurements and ratio calculation of echocardiographic measurements</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup>
							<col/>
							<col/>
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead>
							<tr>
								<th align="left" style="font-weight:normal">Variables</th>
								<th style="font-weight:normal">Medium</th>
								<th style="font-weight:normal">Minimum</th>
								<th style="font-weight:normal">Maximum</th>
								<th style="font-weight:normal">Standard deviation</th>
							</tr>
						</thead>
						<tbody>
							<tr>
								<td>ASD diameter (mm)</td>
								<td align="center">13.46</td>
								<td align="center">2.70</td>
								<td align="center">37.70</td>
								<td align="center">8.33</td>
							</tr>
							<tr>
								<td>MI/ASD - LL</td>
								<td align="center">2.04</td>
								<td align="center">0.62</td>
								<td align="center">6.30</td>
								<td align="center">1.49</td>
							</tr>
							<tr>
								<td>MI/ASD - AP</td>
								<td align="center">2.00</td>
								<td align="center">0.52</td>
								<td align="center">6.80</td>
								<td align="center">1.48</td>
							</tr>
							<tr>
								<td>ASD/septum</td>
								<td align="center">0.30</td>
								<td align="center">0.06</td>
								<td align="center">0.65</td>
								<td align="center">0.15</td>
							</tr>
							<tr>
								<td>QP/QS</td>
								<td align="center">2.56</td>
								<td align="center">1.10</td>
								<td align="center">4.48</td>
								<td align="center">0.99</td>
							</tr>
							<tr>
								<td>TA diameter - LL (mm)</td>
								<td align="center">23.38</td>
								<td align="center">14.40</td>
								<td align="center">38.60</td>
								<td align="center">5.14</td>
							</tr>
							<tr>
								<td>TA Z-score - LL</td>
								<td align="center">+1.40</td>
								<td align="center">-1.63</td>
								<td align="center">+5.28</td>
								<td align="center">1.74</td>
							</tr>
							<tr>
								<td>TA diameter - AP (mm)</td>
								<td align="center">22.48</td>
								<td align="center">10.90</td>
								<td align="center">37.40</td>
								<td align="center">5.77</td>
							</tr>
							<tr>
								<td>TA Z-score - AP</td>
								<td align="center">+1.11</td>
								<td align="center">-2.34</td>
								<td align="center">+3.76</td>
								<td align="center">1.28</td>
							</tr>
							<tr>
								<td>MA diameter - LL (mm)</td>
								<td align="center">18.18</td>
								<td align="center">11.40</td>
								<td align="center">25.80</td>
								<td align="center">3.41</td>
							</tr>
							<tr>
								<td>MA Z-score - LL</td>
								<td align="center">-0.39</td>
								<td align="center">-2.34</td>
								<td align="center">+2.09</td>
								<td align="center">1.15</td>
							</tr>
							<tr>
								<td>MA diameter - AP (mm)</td>
								<td align="center">17.87</td>
								<td align="center">9.80</td>
								<td align="center">25.40</td>
								<td align="center">3.25</td>
							</tr>
							<tr>
								<td>MA Z-score - AP</td>
								<td align="center">-0.07</td>
								<td align="center">-1.89</td>
								<td align="center">+1.93</td>
								<td align="center">0.91</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN2">
							<p>ASD: atrial septal defect; mm: millimeters; MI/ASD: mitral annulus diameter/atrial septal defect diameter; LL: laterolateral; AP: anteroposterior; ASD/septum: atrial septal defect diameter/atrial septum diameter; QP/QS: pulmonary flow/systemic flow; TA: tricuspid annulus; AM: mitral annulus.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
			</p>
			<sec>
				<title>Association and correlation between the variables</title>
				<p>
					<xref ref-type="table" rid="t3">Table 3</xref> shows the comparisons between clinical signs and echocardiographic measurements. There was no association between gender and any of the variables studied, whether in the clinical or echocardiographic context.</p>
				<p>
					<table-wrap id="t3">
						<label>Table 3</label>
						<caption>
							<title>– Comparison between clinical and echocardiographic parameters</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
								<col/>
								<col/>
								<col/>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th align="left" style="font-weight:normal"> </th>
									<th colspan="6" style="font-weight:normal">P-Value</th>
								</tr>
								<tr>
									<th align="left" style="font-weight:normal">Clinical Parameter</th>
									<th style="font-weight:normal">MI/ASD – AP</th>
									<th style="font-weight:normal">MI/ASD – LL</th>
									<th style="font-weight:normal">ASD/septum</th>
									<th style="font-weight:normal">QP/QS</th>
									<th style="font-weight:normal">ASD SIZE according to ASCD*</th>
									<th style="font-weight:normal">TA Z-score</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td>RV impulses</td>
									<td align="center">0.028</td>
									<td align="center">0.018</td>
									<td align="center">0.15</td>
									<td align="center">0.35</td>
									<td align="center">0.025</td>
									<td align="center">0.56</td>
								</tr>
								<tr>
									<td>Splitting of the S2</td>
									<td align="center">&lt; 0.001</td>
									<td align="center">&lt; 0.001</td>
									<td align="center">&lt; 0.001</td>
									<td align="center">0.006</td>
									<td align="center">&lt; 0.001</td>
									<td align="center">0.12</td>
								</tr>
								<tr>
									<td>Pulmonary systolic murmur</td>
									<td align="center">0.015</td>
									<td align="center">0.006</td>
									<td align="center">0.022</td>
									<td align="center">0.037</td>
									<td align="center">0.002</td>
									<td align="center">0.41</td>
								</tr>
								<tr>
									<td>Tricuspid diastolic murmur</td>
									<td align="center">0.055</td>
									<td align="center">0.045</td>
									<td align="center">0.015</td>
									<td align="center">0.016</td>
									<td align="center">0.29</td>
									<td align="center">0.019</td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN3">
								<p>* Fisher’s test. Other variables were analyzed using the unpaired Student’s t-test. MI/ASD: mitral annulus diameter/atrial septal defect diameter; AP: anteroposterior; LL: laterolateral; ASD/septum: atrial septal defect diameter/atrial septal diameter; QP/QS: pulmonary flow/systemic flow; ASCD: subjective assessment of the right chambers; TA: tricuspid annulus; RV: right ventricle; S2: second heart sound.</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
				<p>Twelve ASDs were clinically classified as small, 18 as medium, and 5 as large. The correlation between ASD size by clinical classification and echocardiographic findings is summarized in <xref ref-type="table" rid="t4">Table 4</xref>.</p>
				<p>
					<table-wrap id="t4">
						<label>Table 4</label>
						<caption>
							<title>– Correlation between ASD size by clinical classification and echocardiographic variables</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th align="left" style="font-weight:normal">Echocardiographic variables</th>
									<th style="font-weight:normal">Pearson coefficient</th>
									<th style="font-weight:normal">P-Value</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td>ASD size: subjective assessment of the right chambers</td>
									<td align="center">0.52</td>
									<td align="center">0.001</td>
								</tr>
								<tr>
									<td>ASD size: TA Z-score assessment</td>
									<td align="center">0.26</td>
									<td align="center">0.13</td>
								</tr>
								<tr>
									<td>TA Z-score - Anteroposterior</td>
									<td align="center">0.34</td>
									<td align="center">0.045</td>
								</tr>
								<tr>
									<td>TA Z-score - Laterolateral</td>
									<td align="center">0.34</td>
									<td align="center">0.048</td>
								</tr>
								<tr>
									<td>ASD/septum</td>
									<td align="center">0.56</td>
									<td align="center">&lt;0.001</td>
								</tr>
								<tr>
									<td>QP/QS</td>
									<td align="center">0.62</td>
									<td align="center">0.002</td>
								</tr>
								<tr>
									<td>MI/ASD - Anteroposterior</td>
									<td align="center">-0.58</td>
									<td align="center">&lt;0.001</td>
								</tr>
								<tr>
									<td>MI/ASD - Laterolateral</td>
									<td align="center">-0.61</td>
									<td align="center">&lt;0.001</td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN4">
								<p>ASD: atrial septal defect; TA: tricuspid annulus; ASD/septum: atrial septal defect diameter/atrial septal diameter; QP/QS: pulmonary flow/systemic flow; MI/ASD: mitral annulus diameter/atrial septal defect diameter.</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
				<p>The MI/ASD diameter ratios showed a strong inverse correlation with the ASD/septum measurement. The Pearson coefficient with the anteroposterior and laterolateral measurements was -0.80 (p &lt; 0.001). There was also a strong inverse correlation with the QP/QS measurement, with a Pearson coefficient of -0.71 (p &lt; 0.001) for the anteroposterior measurement and -0.76 (p &lt; 0.001) for the laterolateral measurement.</p>
				<p>The ASD/septum diameter ratio showed a strong correlation with the QP/QS ratio with a Pearson coefficient of 0.63 (p = 0.001).</p>
				<p>Regarding the size of the RV in the subjective assessment, the RV was larger than the LV in 17 subjects, was smaller in 10 subjects, and eight subjects had chambers of equivalent sizes. When assessing the RA, it was larger than the LA in 20 subjects, smaller in eight subjects, and seven subjects had chambers of equivalent sizes. The comparison and correlation between the degree of enlargement of the right chambers and the echocardiographic variables are shown in <xref ref-type="table" rid="t5">Tables 5</xref> and <xref ref-type="table" rid="t6">6</xref>.</p>
				<p>
					<table-wrap id="t5">
						<label>Table 5</label>
						<caption>
							<title>– Comparison between the degree of enlargement of the right chambers according to subjective assessment and echocardiographic variables</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
								<col/>
								<col/>
								<col/>
								<col/>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th align="left" style="font-weight:normal"> </th>
									<th colspan="6" style="font-weight:normal">Degree of enlargement of the right chambers</th>
									<th style="font-weight:normal"> </th>
								</tr>
								<tr>
									<th align="left" style="font-weight:normal">Variables</th>
									<th style="font-weight:normal">Mild</th>
									<th style="font-weight:normal">Standard deviation</th>
									<th style="font-weight:normal">Moderate</th>
									<th style="font-weight:normal">Standard deviation</th>
									<th style="font-weight:normal">Major</th>
									<th style="font-weight:normal">Standard deviation</th>
									<th style="font-weight:normal">p-value (ANOVA)</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td>ASD diameter (mm)</td>
									<td align="center">5.15</td>
									<td align="center">2.27</td>
									<td align="center">11.8</td>
									<td align="center">6.12</td>
									<td align="center">17.37</td>
									<td align="center">8.01</td>
									<td align="center">0.001</td>
								</tr>
								<tr>
									<td>MI/ASD -AP</td>
									<td align="center">4.07</td>
									<td align="center">1.69</td>
									<td align="center">1.78</td>
									<td align="center">0.84</td>
									<td align="center">1.24</td>
									<td align="center">0.48</td>
									<td align="center">&lt; 0.001</td>
								</tr>
								<tr>
									<td>MI/ASD -LL</td>
									<td align="center">4.15</td>
									<td align="center">1.58</td>
									<td align="center">1.86</td>
									<td align="center">0.85</td>
									<td align="center">1.25</td>
									<td align="center">0.52</td>
									<td align="center">&lt; 0.001</td>
								</tr>
								<tr>
									<td>ASD/septum</td>
									<td align="center">0.13</td>
									<td align="center">0.06</td>
									<td align="center">0.29</td>
									<td align="center">0.14</td>
									<td align="center">0.36</td>
									<td align="center">0.13</td>
									<td align="center">&lt; 0.001</td>
								</tr>
								<tr>
									<td>QP/QS</td>
									<td align="center">1.19</td>
									<td align="center">0.10</td>
									<td align="center">2.45</td>
									<td align="center">0.93</td>
									<td align="center">3.05</td>
									<td align="center">0.84</td>
									<td align="center">0.007</td>
								</tr>
								<tr>
									<td>TA Z-score -AP</td>
									<td align="center">-0.17</td>
									<td align="center">0.00</td>
									<td align="center">+1.00</td>
									<td align="center">1.28</td>
									<td align="center">+1.66</td>
									<td align="center">1.04</td>
									<td align="center">0.001</td>
								</tr>
								<tr>
									<td>TA Z-score - LL</td>
									<td align="center">-0.04</td>
									<td align="center">1.30</td>
									<td align="center">+1.17</td>
									<td align="center">0.75</td>
									<td align="center">+2.06</td>
									<td align="center">1.81</td>
									<td align="center">0.01</td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN5">
								<p>ASD: atrial septal defect; mm: millimeters; RA: right atrium; RV: right ventricle; MI/ASD: mitral annulus diameter/atrial septal defect diameter; AP: anteroposterior; LL: laterolateral; ASD/septum: atrial septal defect diameter/atrium septal diameter; QP/QS: pulmonary flow/systemic flow; TA: tricuspid annulus+</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
				<p>
					<table-wrap id="t6">
						<label>Table 6</label>
						<caption>
							<title>– Correlation between the degree of enlargement of the right chambers according to subjective assessment and echocardiographic variables</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th align="left" style="font-weight:normal">Variables</th>
									<th style="font-weight:normal">Pearson coefficient</th>
									<th style="font-weight:normal">P-Value</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td>ASD diameter (mm)</td>
									<td align="center">0.61/0.66 RA/RV</td>
									<td align="center">&lt; 0.001 RA/RV</td>
								</tr>
								<tr>
									<td>MI/ASD -AP</td>
									<td align="center">-0.75</td>
									<td align="center">&lt;0.001</td>
								</tr>
								<tr>
									<td>MI/ASD -LL</td>
									<td align="center">-0.77</td>
									<td align="center">&lt;0.001</td>
								</tr>
								<tr>
									<td>ASD/septum</td>
									<td align="center">0.62</td>
									<td align="center">&lt;0.001</td>
								</tr>
								<tr>
									<td>QP/QS</td>
									<td align="center">0.61</td>
									<td align="center">0.002</td>
								</tr>
								<tr>
									<td>TA Z-score -AP</td>
									<td align="center">0.58</td>
									<td align="center">&lt;0.001</td>
								</tr>
								<tr>
									<td>TA Z-score - LL</td>
									<td align="center">0.50</td>
									<td align="center">0.002</td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN6">
								<p>ASD: atrial septal defect; mm: millimeters; RA: right atrium; RV: right ventricle; MI/ASD: mitral annulus diameter/atrial septal defect diameter; AP: anteroposterior; LL: laterolateral; ASD/septum: atrial septal defect diameter/atrium septal diameter; QP/QS: pulmonary flow/systemic flow; TA: tricuspid annulus.</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
				<p>Considering the TA Z-score to classify the size of the ASDs, 25 were small, 5 were medium, and 5 were large. This classification was not associated with the clinical classification of ASD nor with the echocardiographic classification made according to the subjective assessment of the right chambers.</p>
			</sec>
			<sec>
				<title>Operating characteristic curve</title>
				<p>Applying the operating characteristic curve, considering as the stable variable the classification of the ASD based on the subjective size of the right chambers, an area under the curve of 0.85 was obtained for the ASD/septum ratio. The curve and data with p-value and 95% confidence intervals are shown in <xref ref-type="fig" rid="f03">Figure 2</xref>. The best cutoff point was 0.27, with a sensitivity of 85% and specificity of 86.7% for diagnosing large ASD. The PPV was 76%, and the NPV was 85.2%. The positive likelihood ratio was 6.39.</p>
				<p>
					<fig id="f03">
						<label>Figure 2</label>
						<caption>
							<title>– Operating characteristic curve for the ASD/septum ratio, considering as the stable variable the classification of the ASD based on the subjective size of the right chambers. ROC: receiver operating characteristic.</title>
						</caption>
						<graphic xlink:href="2675-312x-abcimg-38-2-e20240089-gf03.tif"/>
					</fig>
				</p>
				<p>Regarding the variable classification of ASD according to the subjective size of the right chambers, an area under the curve of 0.14 was obtained for the MI/ASD ratio.</p>
			</sec>
		</sec>
		<sec sec-type="discussion">
			<title>Discussion</title>
			<p>The main findings of this study were the strong inverse correlation between the MI/ASD ratio and the clinical classification of the ASD, and the 6.39 probability of diagnosing a large ASD based on an ASD/septum ratio greater than 0.27, according to the subjective size of the right chambers as summarized in the <xref ref-type="fig" rid="f01">Central Illustration</xref>.</p>
			<p>The universal form used by cardiologists to classify ASD size is based on several subjective factors in a clinical and echocardiographic context. The presence of symptoms, changes found during the physical examination, and echocardiographic findings are evaluated. Considering there is great variability in body surface area values in the pediatric population, the ASD diameter alone is not an adequate parameter to quantify the size of the lesion. Other parameters are taken into consideration to assess the size of the lesion, such as the QP/QS ratio,<xref ref-type="bibr" rid="B6"><sup>6</sup></xref> the ASD/interatrial septum diameter ratio, and assessment of the degree of enlargement of the right chambers.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref>
			</p>
			<p>At the time of the study, there was only one study<xref ref-type="bibr" rid="B13"><sup>13</sup></xref> presenting normal values for linear and area measurements of the RA and RV, as indicated by the echocardiogram measurement guideline<xref ref-type="bibr" rid="B7"><sup>7</sup></xref> for the pediatric population. This study had the limitations of being a single-center study carried out only with a Caucasian population aged 0 to 3 years. Therefore, the study could not be incorporated into clinical practice as it did not cover all pediatric age groups. Since then, two new publications<xref ref-type="bibr" rid="B14"><sup>14</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B15"><sup>15</sup></xref> of reference values in pediatrics have emerged. Rajagopal et al., described measurements of the area of the RA, but this was a single-center and retrospective study, the results of which have not yet been incorporated into clinical practice.<xref ref-type="bibr" rid="B14"><sup>14</sup></xref> Gokhroo et al., mentioned reference values for measurements, as recommended by the guideline, but the study was limited to the age group of 5 to 15 years.<xref ref-type="bibr" rid="B15"><sup>15</sup></xref> Therefore, the enlargement of the right chambers is estimated subjectively, visually comparing the area of the right chambers with that of the left chambers in the apical four-chamber view in two-dimensional mode. The QP/QS ratio, despite being an objective measure, is very prone to errors and difficult to measure.<xref ref-type="bibr" rid="B16"><sup>16</sup></xref>
			</p>
			<p>Rao et al., presented the method of classifying the size of the residual shunt after ASD percutaneous closure considering the parameters of flow diameter greater than 2 mm and RV measurements with a percentile &gt; 95% but did not propose a classification of the magnitude of the lesion itself.<xref ref-type="bibr" rid="B17"><sup>17</sup></xref>
			</p>
			<p>There are no studies in the literature that evaluate the ASD/septum ratio to classify ASD size. Lin et al., used measurements of the Interatrial Septum and ASD in two-dimensional and color mode with the use of artificial intelligence in a population with an average age of 3 years and demonstrated good accuracy in detecting defects and cases that could be subjected to percutaneous closure of the lesion by measuring the free edges of the septum. However, this study did not evaluate the degree of hemodynamic repercussion, the classification of the lesion size, or the need for treatment.<xref ref-type="bibr" rid="B18"><sup>18</sup></xref> The measurements chosen in this study were the MI/ASD and ASD/septum ratios, as a way of indexing ASD measurement to a cardiac structure, and should be easy to measure. The ASD was measured using the largest linear diameter.</p>
			<p>Considering that lesions may be asymmetrical, the diameter measurements taken may not necessarily reflect the largest diameter of the lesion. The most reliable measurement would be calculating the ASD area, which is done through 3D echocardiography and magnetic resonance imaging, but these exams are not as widely available in clinical practice.<xref ref-type="bibr" rid="B19"><sup>19</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B20"><sup>20</sup></xref> Thus, to avoid greater bias, diameter measurements were performed with images of good technical quality and using the same subcostal view in all subjects. The subcostal view is very similar to the mid-esophageal bicaval view of the transesophageal echocardiographic examination, which is used to guide percutaneous closure of the ASD with a prosthesis.<xref ref-type="bibr" rid="B6"><sup>6</sup></xref> Boon et al., demonstrated that 2D echocardiographic examination is a reliable method for measuring the diameter of the ASD, especially in cases where the septum is firm, corresponding to 85% of the cases of ostium secundum ASD.<xref ref-type="bibr" rid="B21"><sup>21</sup></xref>
			</p>
			<p>The MI/ASD measurement showed a strong inverse correlation with the clinical classification of ASD and with the classification by subjective assessment of the right chambers. Despite this, it was not possible to define cut-off points for this variable to classify the size of the defect. Although it is intuitive to imagine that the smaller the ratio, the greater the deficit in LV filling and mitral annulus development, it can be speculated that such a relationship is not so linear with the size of the ASD to the point of enabling assertive size calculation.</p>
			<p>The ASD/septum measurement showed a moderate correlation with the clinical classification of ASD and a strong correlation with the classification by subjective assessment of the right chambers. It was not possible to define cutoff points for classifying the magnitude of ASD considering its clinical classification. This finding may be explained by the small number of large ASDs classified by the clinical method. A cutoff point of 0.27 was found for the ASD/septum ratio to identify large ASDs compared with the subjective assessment of the size of the right chambers. The same was not possible for medium-sized ASDs, perhaps also due to the small number of subjects with medium ASD according to the classification by subjective assessment of the right chambers.</p>
			<p>The QP/QS ratio is one of the parameters found in the guidelines for indicating ASD closure in the adult population.<xref ref-type="bibr" rid="B22"><sup>22</sup></xref> It showed a strong correlation with the MI/ASD and ASD/septum measurements and with the clinical and echocardiographic classification of ASD by a subjective assessment of the right chambers. It may have great variability<xref ref-type="bibr" rid="B3"><sup>3</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B4"><sup>4</sup></xref> because of how the relationship is calculated, with four measurements being required: the radius and the velocity-time integral of the RV and LV outflow tract. An error in any of the four measurements can alter the final value of the relationship. Furthermore, the radius measurement is squared, which causes a radius measurement error to also be squared in the calculation.<xref ref-type="bibr" rid="B16"><sup>16</sup></xref> Faherty et al., correlated the QP/QS calculation values on echocardiography with those obtained by oximetry on catheterization in patients with hemodynamically significant ostium secundum ASD and found a weak correlation between the methods, with the echocardiographic method tending to overestimate the values obtained by oximetry.<xref ref-type="bibr" rid="B23"><sup>23</sup></xref>
			</p>
			<p>In clinical practice, it is common to repeat the measurement when the echocardiographer finds a value considered to be incompatible with the other findings. Therefore, the measurement is influenced by a subjective bias. In the study data collection protocol, the number of measurement repetitions for calculating the QP/QS ratio was not limited. Consequently, echocardiographers were free to choose the calculation value they considered to be the most reliable. This subjectivity bias may have contributed to the finding of a strong correlation between this measurement and the other variables studied.</p>
			<p>The TA Z-score measurement showed a weak correlation with the clinical classification of ASD and a moderate correlation with the classification based on a subjective assessment of the right chambers. One explanation for such findings may be the lack of normalization of Z-score reference values for TA measurements in the literature. Despite the standardization of the measurement method of the most recent studies and their larger sample size compared to older studies,<xref ref-type="bibr" rid="B24"><sup>24</sup></xref><sup>-</sup><xref ref-type="bibr" rid="B26"><sup>26</sup></xref> there are still differences between the nomograms, which result in Z-scores that are very discordant with each other. The studies show differences between them, such as the body surface formula used, gender differentiation or lack of it, age range used, and intra-observer and interobserver variability.<xref ref-type="bibr" rid="B27"><sup>27</sup></xref> Snyder et al., demonstrated that there was no strong linear relationship between RV volume on cardiac magnetic resonance imaging and tricuspid valve Z-score on echocardiography in patients in the late postoperative period of Tetralogy of Fallot. Among patients with RV enlargement on MRI, the TA Z-score measurement on echocardiography showed a sensitivity of 45% to identify enlargement, with a Z-score &gt; +2.<xref ref-type="bibr" rid="B28"><sup>28</sup></xref> In the present study, the tricuspid valve diameter Z-score was observed within the normal range despite enlarged RV on a two-dimensional assessment compared to the LV in some subjects.</p>
			<p>The classification of the magnitude of ASD by the TA Z-score value as described in the methodology was not associated with any of the parameters investigated in the physical examination and, consequently, with the clinical classification of ASD, nor it was associated with the classification of ASD according to a subjective assessment of the right chambers. In addition to the already-mentioned variability of Z-score normality values in the pediatric population, the choice of the Z-score range used for classification must be considered. In the study, different Z-score ranges were not compared, and the association of each of them with other methods of classifying ASD size was not evaluated.</p>
			<p>Many of the results found in the study are in agreement with the literature data. Among them, the frequency of findings on physical examination and the proportion between genders.</p>
			<p>The frequency was higher in females, in a proportion of 2.2:1, very close to that described in the literature of 2:1.<xref ref-type="bibr" rid="B2"><sup>2</sup></xref> The percentages found of wide and fixed splitting of the second heart sound (S2), systolic murmur in the pulmonary area, and diastolic murmur in the tricuspid area were 66%, 83%, and 15%, respectively, similar to the values of 66%, 90%, and 12% described in the literature, respectively.<xref ref-type="bibr" rid="B29"><sup>29</sup></xref> Regarding RV impulses, the presence and intensity of such a finding depend greatly on the patient’s biotype.</p>
			<p>The ASD type most frequently found is ostium secundum, responsible for approximately 85% of the cases.<xref ref-type="bibr" rid="B30"><sup>30</sup></xref> In the study, it was the only type found, a finding that can be explained by the small sample size.</p>
			<p>Among the parameters investigated by physical examination, all were associated with the subjective classification of the right chambers, except for the diastolic murmur in the tricuspid area. This fact can be explained by the low sensitivity of this parameter for the diagnosis of ASD.<xref ref-type="bibr" rid="B29"><sup>29</sup></xref>
			</p>
			<sec>
				<title>Limitations</title>
				<p>This study has some limitations because it is a single-center, cross-sectional study with a small sample size and a large age standard deviation. Furthermore, it was not possible to assess the intra-observer and interobserver variability regarding the clinical method and the echocardiographic examination, but the team was previously trained on the measurement protocol. No post hoc test was used to verify significant differences between the echocardiographic parameter measurements and the subjective assessment of the enlargement of the right chambers.</p>
			</sec>
		</sec>
		<sec sec-type="conclusions">
			<title>Conclusions</title>
			<p>The MI/ASD and ASD/septum measurements were associated with ASD size classification concerning the clinical parameters and subjective assessment of the size of the right chambers during an echocardiogram. The measurement of the ASD/septum ratio above 0.27 proved to be useful in identifying large ASDs based on the subjective enlargement of the right chambers, which was not found in small and medium-sized ASDs. It was not possible to define cut-off points for the MI/ASD measurement to classify ASD size. The TA Z-score measurement was not a good parameter for classifying ASD size.</p>
		</sec>
	</body>
	<back>
		<ref-list>
			<title>References</title>
			<ref id="B1">
				<label>1</label>
				<mixed-citation>1. Liu Y, Chen S, Zühlke L, Black GC, Choy MK, Li N, et al. Global Birth Prevalence of Congenital Heart Defects 1970-2017: Updated Systematic Review and Meta-Analysis of 260 Studies. Int J Epidemiol. 2019;48(2):455-63. doi: 10.1093/ije/dyz009.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Liu</surname>
							<given-names>Y</given-names>
						</name>
						<name>
							<surname>Chen</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Zühlke</surname>
							<given-names>L</given-names>
						</name>
						<name>
							<surname>Black</surname>
							<given-names>GC</given-names>
						</name>
						<name>
							<surname>Choy</surname>
							<given-names>MK</given-names>
						</name>
						<name>
							<surname>Li</surname>
							<given-names>N</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Global Birth Prevalence of Congenital Heart Defects 1970-2017: Updated Systematic Review and Meta-Analysis of 260 Studies</article-title>
					<source>Int J Epidemiol</source>
					<year>2019</year>
					<volume>48</volume>
					<issue>2</issue>
					<fpage>455</fpage>
					<lpage>463</lpage>
					<pub-id pub-id-type="doi">10.1093/ije/dyz009</pub-id>
				</element-citation>
			</ref>
			<ref id="B2">
				<label>2</label>
				<mixed-citation>2. Engelfriet P, Mulder BJ. Gender Differences in Adult Congenital Heart Disease. Neth Heart J. 2009;17(11):414-7. doi: 10.1007/BF03086294.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Engelfriet</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Mulder</surname>
							<given-names>BJ</given-names>
						</name>
					</person-group>
					<article-title>Gender Differences in Adult Congenital Heart Disease</article-title>
					<source>Neth Heart J</source>
					<year>2009</year>
					<volume>17</volume>
					<issue>11</issue>
					<fpage>414</fpage>
					<lpage>417</lpage>
					<pub-id pub-id-type="doi">10.1007/BF03086294</pub-id>
				</element-citation>
			</ref>
			<ref id="B3">
				<label>3</label>
				<mixed-citation>3. Quiñones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA; Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. Recommendations for Quantification of Doppler Echocardiography: A Report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr. 2002;15(2):167-84. doi: 10.1067/mje.2002.120202.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Quiñones</surname>
							<given-names>MA</given-names>
						</name>
						<name>
							<surname>Otto</surname>
							<given-names>CM</given-names>
						</name>
						<name>
							<surname>Stoddard</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Waggoner</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Zoghbi</surname>
							<given-names>WA</given-names>
						</name>
						<collab>Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography</collab>
					</person-group>
					<article-title>Recommendations for Quantification of Doppler Echocardiography: A Report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography</article-title>
					<source>J Am Soc Echocardiogr</source>
					<year>2002</year>
					<volume>15</volume>
					<issue>2</issue>
					<fpage>167</fpage>
					<lpage>184</lpage>
					<pub-id pub-id-type="doi">10.1067/mje.2002.120202</pub-id>
				</element-citation>
			</ref>
			<ref id="B4">
				<label>4</label>
				<mixed-citation>4. Lai WW, Mertens LL, Cohen MS, Geva T, editors. Anomalies of the Atrium Septum. Echocardiography In Pediatric And Congenital Heart Disease: From Fetus to Adults. Hoboken: Wiley-Blackwell; 2009.</mixed-citation>
				<element-citation publication-type="book">
					<person-group person-group-type="editor">
						<name>
							<surname>Lai</surname>
							<given-names>WW</given-names>
						</name>
						<name>
							<surname>Mertens</surname>
							<given-names>LL</given-names>
						</name>
						<name>
							<surname>Cohen</surname>
							<given-names>MS</given-names>
						</name>
						<name>
							<surname>Geva</surname>
							<given-names>T</given-names>
						</name>
						<role>editors</role>
					</person-group>
					<chapter-title>Anomalies of the Atrium Septum</chapter-title>
					<source>Echocardiography In Pediatric And Congenital Heart Disease: From Fetus to Adults</source>
					<publisher-loc>Hoboken</publisher-loc>
					<publisher-name>Wiley-Blackwell</publisher-name>
					<year>2009</year>
				</element-citation>
			</ref>
			<ref id="B5">
				<label>5</label>
				<mixed-citation>5. Anderson RH, Baker EI, Penny D, Redington AN, Rigby ML, Wernovsky G. Interatrial Communications. Paediatric Cardiology. Philadelphia: Churchill Livingstone; 2010. p. 523-46.</mixed-citation>
				<element-citation publication-type="book">
					<person-group person-group-type="author">
						<name>
							<surname>Anderson</surname>
							<given-names>RH</given-names>
						</name>
						<name>
							<surname>Baker</surname>
							<given-names>EI</given-names>
						</name>
						<name>
							<surname>Penny</surname>
							<given-names>D</given-names>
						</name>
						<name>
							<surname>Redington</surname>
							<given-names>AN</given-names>
						</name>
						<name>
							<surname>Rigby</surname>
							<given-names>ML</given-names>
						</name>
						<name>
							<surname>Wernovsky</surname>
							<given-names>G</given-names>
						</name>
					</person-group>
					<chapter-title>Interatrial Communications</chapter-title>
					<source>Paediatric Cardiology</source>
					<publisher-loc>Philadelphia</publisher-loc>
					<publisher-name>Churchill Livingstone</publisher-name>
					<year>2010</year>
					<fpage>523</fpage>
					<lpage>546</lpage>
				</element-citation>
			</ref>
			<ref id="B6">
				<label>6</label>
				<mixed-citation>6. Silvestry FE, Cohen MS, Armsby LB, Burkule NJ, Fleishman CE, Hijazi ZM, et al. Guidelines for the Echocardiographic Assessment of Atrial Septal Defect and Patent Foramen Ovale: From the American Society of Echocardiography and Society for Cardiac Angiography and Interventions. J Am Soc Echocardiogr. 2015;28(8):910-58. doi: 10.1016/j.echo.2015.05.015.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Silvestry</surname>
							<given-names>FE</given-names>
						</name>
						<name>
							<surname>Cohen</surname>
							<given-names>MS</given-names>
						</name>
						<name>
							<surname>Armsby</surname>
							<given-names>LB</given-names>
						</name>
						<name>
							<surname>Burkule</surname>
							<given-names>NJ</given-names>
						</name>
						<name>
							<surname>Fleishman</surname>
							<given-names>CE</given-names>
						</name>
						<name>
							<surname>Hijazi</surname>
							<given-names>ZM</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Guidelines for the Echocardiographic Assessment of Atrial Septal Defect and Patent Foramen Ovale: From the American Society of Echocardiography and Society for Cardiac Angiography and Interventions</article-title>
					<source>J Am Soc Echocardiogr</source>
					<year>2015</year>
					<volume>28</volume>
					<issue>8</issue>
					<fpage>910</fpage>
					<lpage>958</lpage>
					<pub-id pub-id-type="doi">10.1016/j.echo.2015.05.015</pub-id>
				</element-citation>
			</ref>
			<ref id="B7">
				<label>7</label>
				<mixed-citation>7. Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK, et al. Recommendations for Quantification Methods During the Performance of a Pediatric Echocardiogram: A Report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr. 2010;23(5):465-95. doi: 10.1016/j.echo.2010.03.019.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lopez</surname>
							<given-names>L</given-names>
						</name>
						<name>
							<surname>Colan</surname>
							<given-names>SD</given-names>
						</name>
						<name>
							<surname>Frommelt</surname>
							<given-names>PC</given-names>
						</name>
						<name>
							<surname>Ensing</surname>
							<given-names>GJ</given-names>
						</name>
						<name>
							<surname>Kendall</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>Younoszai</surname>
							<given-names>AK</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Recommendations for Quantification Methods During the Performance of a Pediatric Echocardiogram: A Report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council</article-title>
					<source>J Am Soc Echocardiogr</source>
					<year>2010</year>
					<volume>23</volume>
					<issue>5</issue>
					<fpage>465</fpage>
					<lpage>495</lpage>
					<pub-id pub-id-type="doi">10.1016/j.echo.2010.03.019</pub-id>
				</element-citation>
			</ref>
			<ref id="B8">
				<label>8</label>
				<mixed-citation>8. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28(1):1-39.e14. doi: 10.1016/j.echo.2014.10.003.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lang</surname>
							<given-names>RM</given-names>
						</name>
						<name>
							<surname>Badano</surname>
							<given-names>LP</given-names>
						</name>
						<name>
							<surname>Mor-Avi</surname>
							<given-names>V</given-names>
						</name>
						<name>
							<surname>Afilalo</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Armstrong</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Ernande</surname>
							<given-names>L</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging</article-title>
					<source>J Am Soc Echocardiogr</source>
					<year>2015</year>
					<volume>28</volume>
					<issue>1</issue>
					<fpage>1</fpage>
					<lpage>39</lpage>
					<comment>e14</comment>
					<pub-id pub-id-type="doi">10.1016/j.echo.2014.10.003</pub-id>
				</element-citation>
			</ref>
			<ref id="B9">
				<label>9</label>
				<mixed-citation>9. zscore.chboston.org [Internet]. Boston: Boston Children's Hospital; 2023 [cited 2025 Mar 7]. Available from:: h <ext-link ext-link-type="uri" xlink:href="https://zscore.chboston.org/">https://zscore.chboston.org/</ext-link>.</mixed-citation>
				<element-citation publication-type="webpage">
					<person-group person-group-type="author">
						<collab>zscore.chboston.org</collab>
					</person-group>
					<comment>Internet</comment>
					<publisher-loc>Boston</publisher-loc>
					<publisher-name>Boston Children's Hospital</publisher-name>
					<year>2023</year>
					<date-in-citation content-type="cited-date">cited 2025 Mar 7</date-in-citation>
					<comment>h</comment>
					<ext-link ext-link-type="uri" xlink:href="https://zscore.chboston.org/">https://zscore.chboston.org/</ext-link>
				</element-citation>
			</ref>
			<ref id="B10">
				<label>10</label>
				<mixed-citation>10. Sluysmans T, Colan SD. Structural Measurements and Adjustments for Growth. In: Lai WW, Mertens LL, Cohen MS, Geva T, editors. Anomalies of the Atrium Septum. Echocardiography In Pediatric And Congenital Heart Disease: From Fetus to Adults. Hoboken: Wiley-Blackwell; 2009. p.158-74.</mixed-citation>
				<element-citation publication-type="book">
					<person-group person-group-type="author">
						<name>
							<surname>Sluysmans</surname>
							<given-names>T</given-names>
						</name>
						<name>
							<surname>Colan</surname>
							<given-names>SD</given-names>
						</name>
					</person-group>
					<chapter-title>Structural Measurements and Adjustments for Growth</chapter-title>
					<person-group person-group-type="editor">
						<name>
							<surname>Lai</surname>
							<given-names>WW</given-names>
						</name>
						<name>
							<surname>Mertens</surname>
							<given-names>LL</given-names>
						</name>
						<name>
							<surname>Cohen</surname>
							<given-names>MS</given-names>
						</name>
						<name>
							<surname>Geva</surname>
							<given-names>T</given-names>
						</name>
						<role>editors</role>
					</person-group>
					<source>Anomalies of the Atrium Septum. Echocardiography In Pediatric And Congenital Heart Disease: From Fetus to Adults</source>
					<publisher-loc>Hoboken</publisher-loc>
					<publisher-name>Wiley-Blackwell</publisher-name>
					<year>2009</year>
					<fpage>158</fpage>
					<lpage>174</lpage>
				</element-citation>
			</ref>
			<ref id="B11">
				<label>11</label>
				<mixed-citation>11. Colan SD. Normal Echocardiographic Values for Cardiovascular Structures. In: Lai WW, Mertens LL, Cohen MS, Geva T, editors. Anomalies of the Atrium Septum. Echocardiography In Pediatric And Congenital Heart Disease: From Fetus to Adults. Hoboken: Wiley-Blackwell; 2009. p. 765-85.</mixed-citation>
				<element-citation publication-type="book">
					<person-group person-group-type="author">
						<name>
							<surname>Colan</surname>
							<given-names>SD</given-names>
						</name>
					</person-group>
					<chapter-title>Normal Echocardiographic Values for Cardiovascular Structures</chapter-title>
					<person-group person-group-type="editor">
						<name>
							<surname>Lai</surname>
							<given-names>WW</given-names>
						</name>
						<name>
							<surname>Mertens</surname>
							<given-names>LL</given-names>
						</name>
						<name>
							<surname>Cohen</surname>
							<given-names>MS</given-names>
						</name>
						<name>
							<surname>Geva</surname>
							<given-names>T</given-names>
						</name>
						<role>editors</role>
					</person-group>
					<source>Anomalies of the Atrium Septum. Echocardiography In Pediatric And Congenital Heart Disease: From Fetus to Adults</source>
					<publisher-loc>Hoboken</publisher-loc>
					<publisher-name>Wiley-Blackwell</publisher-name>
					<year>2009</year>
					<fpage>765</fpage>
					<lpage>785</lpage>
				</element-citation>
			</ref>
			<ref id="B12">
				<label>12</label>
				<mixed-citation>12. Sachdeva, R. Atrial septal defect. In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF, editors. Moss and Adams' Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adult. Philadelphia: Lippincott Williams &amp; Wilkins; 2016. p. 739-56.</mixed-citation>
				<element-citation publication-type="book">
					<person-group person-group-type="author">
						<name>
							<surname>Sachdeva</surname>
							<given-names>R</given-names>
						</name>
					</person-group>
					<chapter-title>Atrial septal defect</chapter-title>
					<person-group person-group-type="editor">
						<name>
							<surname>Allen</surname>
							<given-names>HD</given-names>
						</name>
						<name>
							<surname>Driscoll</surname>
							<given-names>DJ</given-names>
						</name>
						<name>
							<surname>Shaddy</surname>
							<given-names>RE</given-names>
						</name>
						<name>
							<surname>Feltes</surname>
							<given-names>TF</given-names>
						</name>
						<role>editors</role>
					</person-group>
					<source>Moss and Adams' Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adult</source>
					<publisher-loc>Philadelphia</publisher-loc>
					<publisher-name>Lippincott Williams &amp; Wilkins</publisher-name>
					<year>2016</year>
					<fpage>739</fpage>
					<lpage>756</lpage>
				</element-citation>
			</ref>
			<ref id="B13">
				<label>13</label>
				<mixed-citation>13. Cantinotti M, Scalese M, Murzi B, Assanta N, Spadoni I, De Lucia V, et al. Echocardiographic Nomograms for Chamber Diameters and Areas in Caucasian Children. J Am Soc Echocardiogr. 2014;27(12):1279-92.e2. doi: 10.1016/j.echo.2014.08.005.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Cantinotti</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Scalese</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Murzi</surname>
							<given-names>B</given-names>
						</name>
						<name>
							<surname>Assanta</surname>
							<given-names>N</given-names>
						</name>
						<name>
							<surname>Spadoni</surname>
							<given-names>I</given-names>
						</name>
						<name>
							<surname>De Lucia</surname>
							<given-names>V</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Echocardiographic Nomograms for Chamber Diameters and Areas in Caucasian Children</article-title>
					<source>J Am Soc Echocardiogr</source>
					<year>2014</year>
					<volume>27</volume>
					<issue>12</issue>
					<fpage>1279</fpage>
					<lpage>1292</lpage>
					<comment>e2</comment>
					<pub-id pub-id-type="doi">10.1016/j.echo.2014.08.005</pub-id>
				</element-citation>
			</ref>
			<ref id="B14">
				<label>14</label>
				<mixed-citation>14. Rajagopal H, Uppu SC, Weigand J, Lee S, Karnik R, Ko H, et al. Validation of Right Atrial Area as a Measure of Right Atrial Size and Normal Values of in Healthy Pediatric Population by Two-Dimensional Echocardiography. Pediatr Cardiol. 2018;39(5):892-901. doi: 10.1007/s00246-018-1838-3.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Rajagopal</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Uppu</surname>
							<given-names>SC</given-names>
						</name>
						<name>
							<surname>Weigand</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Lee</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Karnik</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Ko</surname>
							<given-names>H</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Validation of Right Atrial Area as a Measure of Right Atrial Size and Normal Values of in Healthy Pediatric Population by Two-Dimensional Echocardiography</article-title>
					<source>Pediatr Cardiol</source>
					<year>2018</year>
					<volume>39</volume>
					<issue>5</issue>
					<fpage>892</fpage>
					<lpage>901</lpage>
					<pub-id pub-id-type="doi">10.1007/s00246-018-1838-3</pub-id>
				</element-citation>
			</ref>
			<ref id="B15">
				<label>15</label>
				<mixed-citation>15. Gokhroo RK, Anantharaj A, Bisht D, Kishor K, Plakkal N, Aghoram R, et al. A Pediatric Echocardiographic Z-Score Nomogram for a Developing Country: Indian Pediatric Echocardiography Study - The Z-score. Ann Pediatr Cardiol. 2017;10(1):31-8. doi: 10.4103/0974-2069.197053.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Gokhroo</surname>
							<given-names>RK</given-names>
						</name>
						<name>
							<surname>Anantharaj</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Bisht</surname>
							<given-names>D</given-names>
						</name>
						<name>
							<surname>Kishor</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>Plakkal</surname>
							<given-names>N</given-names>
						</name>
						<name>
							<surname>Aghoram</surname>
							<given-names>R</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>A Pediatric Echocardiographic Z-Score Nomogram for a Developing Country: Indian Pediatric Echocardiography Study - The Z-score</article-title>
					<source>Ann Pediatr Cardiol</source>
					<year>2017</year>
					<volume>10</volume>
					<issue>1</issue>
					<fpage>31</fpage>
					<lpage>38</lpage>
					<pub-id pub-id-type="doi">10.4103/0974-2069.197053</pub-id>
				</element-citation>
			</ref>
			<ref id="B16">
				<label>16</label>
				<mixed-citation>16. Otto CM. Cardiopatias Congênitas em Adultos: Fundamentos de Ecocardiografia Clínica. Rio de Janeiro: Elsevier; 2010.</mixed-citation>
				<element-citation publication-type="book">
					<person-group person-group-type="author">
						<name>
							<surname>Otto</surname>
							<given-names>CM</given-names>
						</name>
					</person-group>
					<source>Cardiopatias Congênitas em Adultos: Fundamentos de Ecocardiografia Clínica</source>
					<publisher-loc>Rio de Janeiro</publisher-loc>
					<publisher-name>Elsevier</publisher-name>
					<year>2010</year>
				</element-citation>
			</ref>
			<ref id="B17">
				<label>17</label>
				<mixed-citation>17. Rao PS. Role of Echocardiography in the Diagnosis and Interventional Management of Atrial Septal Defects. Diagnostics. 2022;12(6):1494. doi: 10.3390/diagnostics12061494.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Rao</surname>
							<given-names>PS</given-names>
						</name>
					</person-group>
					<article-title>Role of Echocardiography in the Diagnosis and Interventional Management of Atrial Septal Defects</article-title>
					<source>Diagnostics</source>
					<year>2022</year>
					<volume>12</volume>
					<issue>6</issue>
					<size units="pages">1494</size>
					<comment>doi: 10.3390/diagnostics12061494</comment>
				</element-citation>
			</ref>
			<ref id="B18">
				<label>18</label>
				<mixed-citation>18. Lin X, Yang F, Chen Y, Chen X, Wang W, Li W, et al. Echocardiography-Based AI for Detection and Quantification of Atrial Septal Defect. Front Cardiovasc Med. 2023;10:985657. doi: 10.3389/fcvm.2023.985657.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lin</surname>
							<given-names>X</given-names>
						</name>
						<name>
							<surname>Yang</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Chen</surname>
							<given-names>Y</given-names>
						</name>
						<name>
							<surname>Chen</surname>
							<given-names>X</given-names>
						</name>
						<name>
							<surname>Wang</surname>
							<given-names>W</given-names>
						</name>
						<name>
							<surname>Li</surname>
							<given-names>W</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Echocardiography-Based AI for Detection and Quantification of Atrial Septal Defect</article-title>
					<source>Front Cardiovasc Med</source>
					<year>2023</year>
					<volume>10</volume>
					<size units="pages">985657</size>
					<pub-id pub-id-type="doi">10.3389/fcvm.2023.985657</pub-id>
				</element-citation>
			</ref>
			<ref id="B19">
				<label>19</label>
				<mixed-citation>19. Mweri ST, Deng Y, Cheng P, Lin H, Wang H, Mkangara OB, et al. Evaluation of Atrial Septal Defect Using Real-Time Three-Dimensional Echocardiography: Comparison with Surgical Findings. J Huazhong Univ Sci Technolog Med Sci. 2009;29(2):257-9. doi: 10.1007/s11596-009-0225-y.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Mweri</surname>
							<given-names>ST</given-names>
						</name>
						<name>
							<surname>Deng</surname>
							<given-names>Y</given-names>
						</name>
						<name>
							<surname>Cheng</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Lin</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Wang</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Mkangara</surname>
							<given-names>OB</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Evaluation of Atrial Septal Defect Using Real-Time Three-Dimensional Echocardiography: Comparison with Surgical Findings</article-title>
					<source>J Huazhong Univ Sci Technolog Med Sci</source>
					<year>2009</year>
					<volume>29</volume>
					<issue>2</issue>
					<fpage>257</fpage>
					<lpage>259</lpage>
					<pub-id pub-id-type="doi">10.1007/s11596-009-0225-y</pub-id>
				</element-citation>
			</ref>
			<ref id="B20">
				<label>20</label>
				<mixed-citation>20. Beerbaum P, Körperich H, Esdorn H, Blanz U, Barth P, Hartmann J, et al. Atrial Septal Defects in Pediatric Patients: Noninvasive Sizing with Cardiovascular MR Imaging. Radiology. 2003;228(2):361-9. doi: 10.1148/radiol.2282020798.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Beerbaum</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Körperich</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Esdorn</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Blanz</surname>
							<given-names>U</given-names>
						</name>
						<name>
							<surname>Barth</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Hartmann</surname>
							<given-names>J</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Atrial Septal Defects in Pediatric Patients: Noninvasive Sizing with Cardiovascular MR Imaging</article-title>
					<source>Radiology</source>
					<year>2003</year>
					<volume>228</volume>
					<issue>2</issue>
					<fpage>361</fpage>
					<lpage>369</lpage>
					<pub-id pub-id-type="doi">10.1148/radiol.2282020798</pub-id>
				</element-citation>
			</ref>
			<ref id="B21">
				<label>21</label>
				<mixed-citation>21. Boon I, Vertongen K, Paelinck BP, Demulier L, van Berendoncks A, Maeyer C, et al. How to Size ASDs for Percutaneous Closure. Pediatr Cardiol. 2018;39(1):168-75. doi: 10.1007/s00246-017-1743-1.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Boon</surname>
							<given-names>I</given-names>
						</name>
						<name>
							<surname>Vertongen</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>Paelinck</surname>
							<given-names>BP</given-names>
						</name>
						<name>
							<surname>Demulier</surname>
							<given-names>L</given-names>
						</name>
						<name>
							<surname>van Berendoncks</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Maeyer</surname>
							<given-names>C</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>How to Size ASDs for Percutaneous Closure</article-title>
					<source>Pediatr Cardiol</source>
					<year>2018</year>
					<volume>39</volume>
					<issue>1</issue>
					<fpage>168</fpage>
					<lpage>175</lpage>
					<pub-id pub-id-type="doi">10.1007/s00246-017-1743-1</pub-id>
				</element-citation>
			</ref>
			<ref id="B22">
				<label>22</label>
				<mixed-citation>22. Stout KK, Daniels CJ, Aboulhosn JA, Bozkurt B, Broberg CS, Colman JM, et al. 2018 AHA/ACC Guideline for the Management of Adults with Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(14):e698-e800. doi: 10.1161/CIR.0000000000000603.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Stout</surname>
							<given-names>KK</given-names>
						</name>
						<name>
							<surname>Daniels</surname>
							<given-names>CJ</given-names>
						</name>
						<name>
							<surname>Aboulhosn</surname>
							<given-names>JA</given-names>
						</name>
						<name>
							<surname>Bozkurt</surname>
							<given-names>B</given-names>
						</name>
						<name>
							<surname>Broberg</surname>
							<given-names>CS</given-names>
						</name>
						<name>
							<surname>Colman</surname>
							<given-names>JM</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>2018 AHA/ACC Guideline for the Management of Adults with Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines</article-title>
					<source>Circulation</source>
					<year>2019</year>
					<volume>139</volume>
					<issue>14</issue>
					<fpage>e698</fpage>
					<lpage>e800</lpage>
					<pub-id pub-id-type="doi">10.1161/CIR.0000000000000603</pub-id>
				</element-citation>
			</ref>
			<ref id="B23">
				<label>23</label>
				<mixed-citation>23. Faherty E, Rajagopal H, Lee S, Love B, Srivastava S, Parness IA, et al. Correlation of Transthoracic Echocardiography-Derived Pulmonary to Systemic Flow Ratio with Hemodynamically Estimated Left to Right Shunt in Atrial Septal Defects. Ann Pediatr Cardiol. 2022;15(1):20-6. doi: 10.4103/apc.apc_139_21.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Faherty</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Rajagopal</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Lee</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Love</surname>
							<given-names>B</given-names>
						</name>
						<name>
							<surname>Srivastava</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Parness</surname>
							<given-names>IA</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Correlation of Transthoracic Echocardiography-Derived Pulmonary to Systemic Flow Ratio with Hemodynamically Estimated Left to Right Shunt in Atrial Septal Defects</article-title>
					<source>Ann Pediatr Cardiol</source>
					<year>2022</year>
					<volume>15</volume>
					<issue>1</issue>
					<fpage>20</fpage>
					<lpage>26</lpage>
					<conf-loc>doi</conf-loc>
					<pub-id pub-id-type="doi">10.4103/apc.apc_139_21</pub-id>
				</element-citation>
			</ref>
			<ref id="B24">
				<label>24</label>
				<mixed-citation>24. Sluysmans T, Colan SD. Theoretical and Empirical Derivation of Cardiovascular Allometric Relationships in Children. J Appl Physiol. 2005;99(2):445-57. doi: 10.1152/japplphysiol.01144.2004.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Sluysmans</surname>
							<given-names>T</given-names>
						</name>
						<name>
							<surname>Colan</surname>
							<given-names>SD</given-names>
						</name>
					</person-group>
					<article-title>Theoretical and Empirical Derivation of Cardiovascular Allometric Relationships in Children</article-title>
					<source>J Appl Physiol</source>
					<year>2005</year>
					<volume>99</volume>
					<issue>2</issue>
					<fpage>445</fpage>
					<lpage>457</lpage>
					<pub-id pub-id-type="doi">10.1152/japplphysiol.01144.2004</pub-id>
				</element-citation>
			</ref>
			<ref id="B25">
				<label>25</label>
				<mixed-citation>25. Zilberman MV, Khoury PR, Kimball RT. Two-Dimensional Echocardiographic Valve Measurements in Healthy Children: Gender-Specific Differences. Pediatr Cardiol. 2005;26(4):356-60. doi: 10.1007/s00246-004-0736-z.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Zilberman</surname>
							<given-names>MV</given-names>
						</name>
						<name>
							<surname>Khoury</surname>
							<given-names>PR</given-names>
						</name>
						<name>
							<surname>Kimball</surname>
							<given-names>RT</given-names>
						</name>
					</person-group>
					<article-title>Two-Dimensional Echocardiographic Valve Measurements in Healthy Children: Gender-Specific Differences</article-title>
					<source>Pediatr Cardiol</source>
					<year>2005</year>
					<volume>26</volume>
					<issue>4</issue>
					<fpage>356</fpage>
					<lpage>360</lpage>
					<pub-id pub-id-type="doi">10.1007/s00246-004-0736-z</pub-id>
				</element-citation>
			</ref>
			<ref id="B26">
				<label>26</label>
				<mixed-citation>26. Pettersen MD, Du W, Skeens ME, Humes RA. Regression Equations for Calculation of z Scores of Cardiac Structures in a Large Cohort of Healthy Infants, Children, and Adolescents: An Echocardiographic Study. J Am Soc Echocardiogr. 2008;21(8):922-34. doi: 10.1016/j.echo.2008.02.006.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Pettersen</surname>
							<given-names>MD</given-names>
						</name>
						<name>
							<surname>Du</surname>
							<given-names>W</given-names>
						</name>
						<name>
							<surname>Skeens</surname>
							<given-names>ME</given-names>
						</name>
						<name>
							<surname>Humes</surname>
							<given-names>RA</given-names>
						</name>
					</person-group>
					<article-title>Regression Equations for Calculation of z Scores of Cardiac Structures in a Large Cohort of Healthy Infants, Children, and Adolescents: An Echocardiographic Study</article-title>
					<source>J Am Soc Echocardiogr</source>
					<year>2008</year>
					<volume>21</volume>
					<issue>8</issue>
					<fpage>922</fpage>
					<lpage>934</lpage>
					<pub-id pub-id-type="doi">10.1016/j.echo.2008.02.006</pub-id>
				</element-citation>
			</ref>
			<ref id="B27">
				<label>27</label>
				<mixed-citation>27. Cantinotti M, Scalese M, Molinaro S, Murzi B, Passino C. Limitations of Current Echocardiographic Nomograms for Left Ventricular, Valvular, and Arterial Dimensions in Children: A Critical Review. J Am Soc Echocardiogr. 2012;25(2):142-52. doi: 10.1016/j.echo.2011.10.016.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Cantinotti</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Scalese</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Molinaro</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Murzi</surname>
							<given-names>B</given-names>
						</name>
						<name>
							<surname>Passino</surname>
							<given-names>C</given-names>
						</name>
					</person-group>
					<article-title>Limitations of Current Echocardiographic Nomograms for Left Ventricular, Valvular, and Arterial Dimensions in Children: A Critical Review</article-title>
					<source>J Am Soc Echocardiogr</source>
					<year>2012</year>
					<volume>25</volume>
					<issue>2</issue>
					<fpage>142</fpage>
					<lpage>152</lpage>
					<pub-id pub-id-type="doi">10.1016/j.echo.2011.10.016</pub-id>
				</element-citation>
			</ref>
			<ref id="B28">
				<label>28</label>
				<mixed-citation>28. Snyder K, Drant S, Carris E, Christopher A, Allada V. Tricuspid Valve Size Relationship to Right Ventricular Volume in Post-Operative Tetralogy of Fallot Patients. Pediatr Cardiol. 2022;43(4):887-93. doi: 10.1007/s00246-021-02800-0.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Snyder</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>Drant</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Carris</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Christopher</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Allada</surname>
							<given-names>V</given-names>
						</name>
					</person-group>
					<article-title>Tricuspid Valve Size Relationship to Right Ventricular Volume in Post-Operative Tetralogy of Fallot Patients</article-title>
					<source>Pediatr Cardiol</source>
					<year>2022</year>
					<volume>43</volume>
					<issue>4</issue>
					<fpage>887</fpage>
					<lpage>893</lpage>
					<pub-id pub-id-type="doi">10.1007/s00246-021-02800-0</pub-id>
				</element-citation>
			</ref>
			<ref id="B29">
				<label>29</label>
				<mixed-citation>29. Geggel RL. Clinical Detection of Hemodynamically Significant Isolated Secundum Atrial Septal Defect. J Pediatr. 2017;190:261-4.e1. doi: 10.1016/j.jpeds.2017.07.037.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Geggel</surname>
							<given-names>RL</given-names>
						</name>
					</person-group>
					<article-title>Clinical Detection of Hemodynamically Significant Isolated Secundum Atrial Septal Defect</article-title>
					<source>J Pediatr</source>
					<year>2017</year>
					<volume>190</volume>
					<fpage>261</fpage>
					<lpage>4.e1</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jpeds.2017.07.037</pub-id>
				</element-citation>
			</ref>
			<ref id="B30">
				<label>30</label>
				<mixed-citation>30. Naqvi N, McCarthy KP, Ho SY. Anatomy of the Atrial Septum and Interatrial Communications. J Thorac Dis. 2018;10(Suppl 24):2837-47. doi: 10.21037/jtd.2018.02.18.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Naqvi</surname>
							<given-names>N</given-names>
						</name>
						<name>
							<surname>McCarthy</surname>
							<given-names>KP</given-names>
						</name>
						<name>
							<surname>Ho</surname>
							<given-names>SY</given-names>
						</name>
					</person-group>
					<article-title>Anatomy of the Atrial Septum and Interatrial Communications</article-title>
					<source>J Thorac Dis</source>
					<year>2018</year>
					<volume>10</volume>
					<supplement>Suppl 24</supplement>
					<fpage>2837</fpage>
					<lpage>2847</lpage>
					<pub-id pub-id-type="doi">10.21037/jtd.2018.02.18</pub-id>
				</element-citation>
			</ref>
		</ref-list>
		<fn-group>
			<fn fn-type="other">
				<label>Study Association:</label>
				<p> This article is part of the thesis of master submitted by Lívia de Castro Ribeiro, from Universidade Federal de Minas Gerais.</p>
			</fn>
			<fn fn-type="other">
				<label>Ethics Approval and Consent to Participate:</label>
				<p> This study was approved by the Ethics Committee of the UFMG under the protocol number 53353116.3.0000.5149. 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 fn-type="financial-disclosure">
				<label>Sources of Funding:</label>
				<p> There were no external funding sources for this study.</p>
			</fn>
		</fn-group>
	</back>
	<sub-article article-type="translation" id="TRpt" xml:lang="pt">
		<front-stub>
			<article-id pub-id-type="doi">10.36660/abcimg.20240089</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Artigo Original</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Classificação do Tamanho da Comunicação Interatrial Segundo Parâmetros Ecocardiográficos e Sua Associação com o Quadro Clínico Em Pediatria</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-0502-7371</contrib-id>
					<name>
						<surname>Ribeiro</surname>
						<given-names>Lívia de Castro</given-names>
					</name>
					<role>obtenção de dados</role>
					<role>análise e interpretação dos dados e redação do manuscrito</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-0963-948X</contrib-id>
					<name>
						<surname>Silva</surname>
						<given-names>Rose Mary Ferreira Lisboa da</given-names>
					</name>
					<role>análise estatística</role>
					<role>revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0003-2481-2647</contrib-id>
					<name>
						<surname>Tonelli</surname>
						<given-names>Henrique de Assis Fonseca</given-names>
					</name>
					<role>Concepção e desenho da pesquisa</role>
					<role>obtenção de dados</role>
					<role>revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0001-8288-7116</contrib-id>
					<name>
						<surname>Guimarães</surname>
						<given-names>Adriana Furletti Machado</given-names>
					</name>
					<role>obtenção de dados</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-3059-7480</contrib-id>
					<name>
						<surname>Araújo</surname>
						<given-names>Fátima Derlene da Rocha</given-names>
					</name>
					<role>obtenção de dados</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0001-5526-7915</contrib-id>
					<name>
						<surname>Meira</surname>
						<given-names>Zilda Maria Alves</given-names>
					</name>
					<role>obtenção de dados</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-4610-6439</contrib-id>
					<name>
						<surname>Castilho</surname>
						<given-names>Sandra Regina Tolentino</given-names>
					</name>
					<role>obtenção de dados</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Conde</surname>
						<given-names>Alan Alvarez</given-names>
					</name>
					<role>obtenção de dados</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0009-4455-6530</contrib-id>
					<name>
						<surname>Valadares</surname>
						<given-names>Lícia Campos</given-names>
					</name>
					<role>obtenção de dados</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff1002">
				<label>1</label>
				<country country="BR">Brasil</country>
				<institution content-type="original">Universidade Federal de Minas Gerais, Belo Horizonte, MG – Brasil</institution>
			</aff>
			<author-notes>
				<corresp id="c01002">
					<label>Correspondência</label>: Livia de Castro Ribeiro • Hospital das Clínicas da Universidade Federal de Minas Gerais. Rua Alfredo Balena, 110. CEP: 30130-100. Belo Horizonte, MG – Brasil E-mail: liviadecastromed85@gmail.com </corresp>
				<fn fn-type="edited-by">
					<label>Editor responsável pela revisão:</label>
					<p>Karen Saori Shiraishi Sawamura</p>
				</fn>
				<fn fn-type="conflict">
					<label>Potencial Conflito de Interesse:</label>
					<p>Declaro não haver conflito de interesses pertinentes.</p>
				</fn>
			</author-notes>
			<abstract>
				<title>Resumo</title>
				<sec>
					<title>Fundamento</title>
					<p> Há poucos estudos que utilizam medidas ecocardiográficas lineares para classificação do tamanho da Comunicação Interatrial (CIA).</p>
				</sec>
				<sec>
					<title>Objetivos</title>
					<p> Investigar relação entre repercussão hemodinâmica da CIA e medidas da relação do diâmetro da CIA (MI/CIA) com diâmetro do anel mitral, bem como o diâmetro do septo interatrial (CIA/septo) e descrever pontos de corte que permitam classificar o tamanho do defeito.</p>
				</sec>
				<sec>
					<title>Métodos</title>
					<p> Estudo observacional, prospectivo, transversal, incluindo participantes com idade entre 1 mês e 18 anos, diagnosticados com CIA isolada. Repercussão hemodinâmica foi quantificada pela avaliação clínica, Z-escore do anel tricúspide (AT), avaliação subjetiva da dilatação de câmaras direitas, relação entre fluxos sistêmico e pulmonar (QP/QS) à ecocardiografia e estudada sua associação com medidas CIA/septo e MI/CIA. Um valor de p &lt; 0,05 foi considerado estatisticamente significante.</p>
				</sec>
				<sec>
					<title>Resultados</title>
					<p> Trinta e cinco participantes, média de idade 6,3 anos, 69% feminino, média da CIA 13,5 mm. Houve correlação entre MI/CIA com a classificação clínica da CIA (Pearson:-0,61; p &lt; 0,001), CIA/septo (Pearson:-0,80; p &lt; 0,001), QP/QS (-0,76; p &lt; 0,001). Houve correlação de CIA/septo com a classificação clínica da CIA (Pearson:0,56; p &lt; 0,001), QP/QS (0,63; p = 0,001), avaliação subjetiva de câmaras direitas (0,62; p &lt; 0,001) e fraca correlação com Z-escore do AT (0,35; p = 0,04). Pela curva de operação característica para variável estável de classificação da CIA, com base no tamanho subjetivo de câmaras direitas, revelou uma área de 0,85 para a razão CIA/septo (p = 0,001). O ponto de corte de 0,27 para CIA grande apresentou sensibilidade de 85%, especificidade de 86,7%, valor preditivo positivo (VPP) de 86%, negativo de 85,2%, razão de verossimilhança positiva de 6,39.</p>
				</sec>
				<sec>
					<title>Conclusões</title>
					<p> CIA/septo associou-se à repercussão hemodinâmica da CIA e mostrou-se útil na detecção de CIA grande.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="pt">
				<kwd>Comunicação Interatrial</kwd>
				<kwd>Ecocardiografia</kwd>
				<kwd>Valva Tricúspide</kwd>
				<kwd>Septo Interatrial</kwd>
			</kwd-group>
		</front-stub>
		<body>
			<p>
					<fig id="f01002">
						<label>Figura Central:</label>
						<caption>
							<title>Classificação do Tamanho da Comunicação Interatrial Segundo Parâmetros Ecocardiográficos e Sua Associação com o Quadro Clínico Em Pediatria</title>
							<p>CIA: Comunicação Interatrial; VPP: valor preditivo positivo; ROC:curva de operação característica; RVS: razão de verossimilhança; VM: valva mitral; VPN: valor preditivo negativo</p>
						</caption>
						<graphic xlink:href="2675-312x-abcimg-38-2-e20240089-gf01-pt.tif"/>
					</fig>
				</p>
			<sec sec-type="intro">
				<title>Introdução</title>
				<p>A Comunicação Interatrial (CIA) é uma alteração estrutural do coração congênita que permite a mistura de sangue entre os átrios através da falha no Septo Atrial ou em estruturas adjacentes. A CIA isolada é a terceira malformação cardíaca mais frequente, correspondendo a cerca de 15% do total de cardiopatias congênitas.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> A prevalência da CIA é duas vezes maior entre os indivíduos do sexo feminino se comparado aos do sexo masculino.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> O exame ecocardiográfico transtorácico é o método mais utilizado para diagnóstico e avaliação da CIA na população pediátrica, sendo suficiente para definição adequada da lesão e suas repercussões hemodinâmicas na maioria das vezes. Para a descrição dos defeitos em relação ao tamanho, são utilizadas comumente a medida linear do defeito, sua relação com o tamanho do Septo Atrial (CIA/septo), a repercussão em câmaras direitas (sinais de sobrecarga volumétrica) e a medida da relação fluxo pulmonar/fluxo sistêmico (QP/QS). A medida CIA/septo tem sido utilizada informalmente na prática clínica, sem sistematização por meio de estudo e sem pontos de corte confiáveis para classificação de tamanho. A medida do QP/QS ao exame ecocardiográfico encerra grande limitação representada pela baixa reprodutibilidade<sup><xref ref-type="bibr" rid="B3">3</xref></sup> e execução laboriosa.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Os objetivos do estudo foram investigar, por meio da avaliação clínica e ecocardiográfica, a relação entre a repercussão hemodinâmica da CIA e as medidas da relação entre o diâmetro do Anel Mitral e o diâmetro da CIA (MI/CIA) e (CIA/septo) e descrever os pontos de corte dessas relações que permitissem a classificação do defeito quanto a sua magnitude.</p>
			</sec>
			<sec sec-type="methods">
				<title>Métodos</title>
				<p>Tratou-se de um estudo observacional, prospectivo e transversal. A população foi constituída por 35 participantes, de CIA isolada com orifício único ao exame ecocardiográfico, de ambos sexos, com idades entre 1 mês e 18 anos. Tanto o projeto de pesquisa quanto os Termos de Consentimento e Assentimento Livre e Esclarecido (TCLE e TALE) foram aprovados pelo Comitê de Ética e Pesquisa do hospital universitário, no qual foi feita a pesquisa. Após o aceite e assinatura dos termos, os participantes foram submetidos a exame ecocardiográfico e avaliação clínica. Foram excluídos aqueles com cardiopatias congênitas significativas (excluindo-se forame oval permeável, regurgitações mitral, tricúspide e aórtica discretas, valva aórtica bicúspide sem estenose), cardiomiopatia (primária ou secundária), anemia crônica e hipertensão pulmonar não atribuída à presença da CIA. A amostragem foi por conveniência.</p>
				<p>O exame ecocardiográfico foi realizado com um aparelho TOSHIBA APLIO 400, com transdutores pediátrico e adulto de 2,5 MHz e 5,0 MHz de frequência, respectivamente, por ecocardiografista pediátrico, e a avaliação clínica por um cardiologista pediátrico, ambos integrantes da equipe, e de forma cega com relação à avaliação clínica e vice-versa. A avaliação clínica foi realizada no mesmo dia da avaliação ecocardiográfica, imediatamente após esta. A avaliação do grau de repercussão em câmaras direitas foi realizada de forma subjetiva, comparando-se as áreas do Átrio Direito (AD) com o Átrio Esquerdo (AE) e áreas do Ventrículo Direito (VD) com o Ventrículo Esquerdo (VE), ao modo bidimensional, no corte apical quatro câmaras,<sup><xref ref-type="bibr" rid="B5">5</xref></sup> uma vez que medidas lineares e de área de AD e VD não foram consistentemente padronizadas para a população pediátrica.<sup><xref ref-type="bibr" rid="B6">6</xref>-<xref ref-type="bibr" rid="B8">8</xref></sup> Comparativamente, se as câmaras direitas apresentavam área menor, igual ou maior que as câmaras esquerdas, o aumento foi considerado ausente ou leve, moderado ou importante, respectivamente. As medidas do septo interatrial e do diâmetro da CIA foram realizadas ao modo bidimensional, no corte subcostal do Septo Atrial, com auxílio do Color Doppler para identificação das bordas do defeito.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> Para a medida do Septo Atrial, foi padronizada a distância vertical entre as desembocaduras das cavas. A medida da CIA foi realizada na região de maior distância entre as bordas ao longo do ciclo cardíaco. Foi calculada a relação CIA/septo a fim de comparar tal medida com a repercussão hemodinâmica. A magnitude do <bold>shunt</bold> através da CIA foi estimada pelo cálculo da relação fluxo sistêmico/fluxo pulmonar (QP/QS).<sup><xref ref-type="bibr" rid="B6">6</xref></sup> As medidas de diâmetros dos Anéis Mitral e Tricúspide foram realizadas ao modo bidimensional, na protodiástole. Foram utilizados o corte paraesternal em longitudinal eixo longo de VE e via de entrada de VD para medidas dos diâmetros anteroposteriores (mitral e tricúspide, respectivamente), além do corte apical de quatro câmaras para medidas dos diâmetros laterolaterais<sup><xref ref-type="bibr" rid="B7">7</xref></sup> (<xref ref-type="fig" rid="f02002">Figura 1</xref>). Os diâmetros foram indexados na forma de Z-escore utilizando-se a referência de Boston.<sup><xref ref-type="bibr" rid="B9">9</xref>-<xref ref-type="bibr" rid="B11">11</xref></sup> Os valores de Z escore de Anel Tricúspide (AT) também foram utilizados para classificação do grau de repercussão da CIA em câmaras direitas. Foi calculada a relação MI/CIA a fim de compará-la com a repercussão hemodinâmica. A classificação do tamanho da CIA pelos critérios ecocardiográficos foi realizada por análise subjetiva e Z-escore: CIA pequena: área das câmaras direitas menor que a área das câmaras esquerdas e Z-escore do AT de +2 a +2,5; CIA média: área das câmaras direitas igual à área das câmaras esquerdas e Z escore do AT de +2,5 a +3; CIA grande: área das câmaras direitas maior que a área das câmaras esquerdas e Z-score do AT &gt; +3.</p>
				<p>
					<fig id="f02002">
						<label>Figura 1</label>
						<caption>
							<title>– Medida do septo interatrial, da CIA e anéis mitral e tricúspide ao exame ecocardiográfico. AD: átrio direito; AE: átrio esquerdo; VE: ventrículo esquerdo; VD: ventrículo direito; CIA: Comunicação Interatrial. VM: valva mitral; VT: valva tricúspide; VCS: veia cava superior; VCI: veia cava inferior.</title>
						</caption>
						<graphic xlink:href="2675-312x-abcimg-38-2-e20240089-gf02-pt.tif"/>
					</fig>
				</p>
				<p>A avaliação clínica consistiu em exame do sistema cardiovascular orientado quanto aos critérios que permitissem inferir sobre o tamanho da CIA.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> A classificação quanto ao tamanho da CIA pela avaliação clínica foi feita conforme a <xref ref-type="table" rid="t1002">Tabela 1</xref> e foi considerada a presença de pelo menos três dos quatro achados para cada coluna.</p>
				<p>
					<table-wrap id="t1002">
						<label>Tabela 1</label>
						<caption>
							<title>– Classificação do tamanho da CIA conforme critérios clínicos</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th align="left" style="font-weight:normal"> </th>
									<th align="left" colspan="3">Classificação do tamanho</th>
								</tr>
								<tr>
									<th align="left">Parâmetro Clínico</th>
									<th align="left">Pequena</th>
									<th align="left">Média</th>
									<th align="left">Grande</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td>Impulsão em BEEI e região subxifóide</td>
									<td>Ausente</td>
									<td>Presente</td>
									<td>Presente</td>
								</tr>
								<tr>
									<td>Desdobramento de segunda bulha</td>
									<td>Fisiológico</td>
									<td>Fixo</td>
									<td>Fixo</td>
								</tr>
								<tr>
									<td>Sopro sistólico ejetivo em foco pulmonar</td>
									<td>Ausente ou grau I/VI</td>
									<td>Grau II/VI</td>
									<td>Grau &gt; III/VI</td>
								</tr>
								<tr>
									<td>Sopro diastólico em foco tricúspide</td>
									<td>Ausente</td>
									<td>Ausente</td>
									<td>Presente</td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN1002">
								<p>BEEI: borda esternal esquerda inferior.</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
				<p>Análise estatística: A análise estatística foi feita utilizando-se o software <bold>Statistical Package for Social Science</bold> (SPSS) versão 16.0. Os resultados foram expressos em números e proporções para variáveis categóricas e médias ± desvio-padrão para variáveis contínuas. A confirmação de distribuição normal das variáveis foi verificada pelo teste Shapiro-Wilk. As proporções foram comparadas por meio do teste de Qui-quadrado ou do teste de Fisher quando apropriado. Para dados contínuos, foi utilizado o teste T de Student não pareado, para duas variáveis ou o teste de ANOVA One-Way, para comparar três ou mais variáveis. O coeficiente de Pearson foi usado para verificar a correlação entre variáveis. A correlação por meio do coeficiente foi considerada muito fraca (0,00–0,20), fraca (0,21–0,40), moderada (0,41–0,60), forte (0,61–0,80) e muito forte (0,81–1,00), seja positiva ou inversa. Foi aplicada a curva de operação característica para avaliar sensibilidade, especificidade, VPP, Valor Preditivo Negativo (VPN) e razão de verossimilhança positiva da relação CIA/septo, considerando-se a magnitude do defeito septal. Um valor-p &lt; 0,05 foi considerado estatisticamente significante.</p>
			</sec>
			<sec sec-type="results">
				<title>Resultados</title>
				<p>Entre os 35 participantes, 24 (69%) eram do sexo feminino. A média de idade foi de 6,3± 3,9 anos, variando de 0,4 a 17,2 anos. As médias de peso, altura e superfície corporal foram de 21,2 kg, 112 cm e 0,8 m<sup><xref ref-type="bibr" rid="B2">2</xref></sup>, respectivamente. Comorbidades estavam presentes em 14% dos participantes (n = 5), sendo elas: asma (3), síndrome genética em investigação (1) e atraso do desenvolvimento neuropsicomotor em propedêutica (1).</p>
				<p>Quanto aos achados ao exame físico, 14 participantes (40%) apresentavam desdobramento fixo de segunda bulha e 5 (14%) sopro diastólico em foco tricúspide. Sopro sistólico em foco pulmonar não foi detectado em 6 participantes, foi de grau II em 16 (46%) e de grau III ≥ em 13 (37%). Quanto à impulsão de VD, não foi detectada em 19 (54%) participantes.</p>
				<p>Ao exame ecocardiográfico, todos os participantes apresentavam CIA tipo <bold>ostium secundum</bold>. Os dados coletados estão sumarizados na <xref ref-type="table" rid="t2002">Tabela 2</xref>.</p>
				<p>
					<table-wrap id="t2002">
						<label>Tabela 2</label>
						<caption>
							<title>– Medidas e cálculo de relação entre medidas ecocardiográficas</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
								<col/>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th align="left">Variáveis</th>
									<th align="left">Média</th>
									<th align="left">Mínimo</th>
									<th align="left">Máximo</th>
									<th align="left">Desvio-padrão</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td>Diâmetro CIA (mm)</td>
									<td>13,46</td>
									<td>2,70</td>
									<td>37,70</td>
									<td>8,33</td>
								</tr>
								<tr>
									<td>MI / CIA - LL</td>
									<td>2,04</td>
									<td>0,62</td>
									<td>6,30</td>
									<td>1,49</td>
								</tr>
								<tr>
									<td>MI/CIA - AP</td>
									<td>2,00</td>
									<td>0,52</td>
									<td>6,80</td>
									<td>1,48</td>
								</tr>
								<tr>
									<td>CIA/septo</td>
									<td>0,30</td>
									<td>0,06</td>
									<td>0,65</td>
									<td>0,15</td>
								</tr>
								<tr>
									<td>QP/QS</td>
									<td>2,56</td>
									<td>1,10</td>
									<td>4,48</td>
									<td>0,99</td>
								</tr>
								<tr>
									<td>Diâmetro AT - LL (mm)</td>
									<td>23,38</td>
									<td>14,40</td>
									<td>38,60</td>
									<td>5,14</td>
								</tr>
								<tr>
									<td>Z-escore AT - LL</td>
									<td>+1,40</td>
									<td>-1,63</td>
									<td>+5,28</td>
									<td>1,74</td>
								</tr>
								<tr>
									<td>Diâmetro AT - AP (mm)</td>
									<td>22,48</td>
									<td>10,90</td>
									<td>37,40</td>
									<td>5,77</td>
								</tr>
								<tr>
									<td>Z-escore AT - AP</td>
									<td>+1,11</td>
									<td>-2,34</td>
									<td>+3,76</td>
									<td>1,28</td>
								</tr>
								<tr>
									<td>Diâmetro AM - LL (mm)</td>
									<td>18,18</td>
									<td>11,40</td>
									<td>25,80</td>
									<td>3,41</td>
								</tr>
								<tr>
									<td>Z-escore AM - LL</td>
									<td>-0,39</td>
									<td>-2,34</td>
									<td>+2,09</td>
									<td>1,15</td>
								</tr>
								<tr>
									<td>Diâmetro AM - AP (mm)</td>
									<td>17,87</td>
									<td>9,80</td>
									<td>25,40</td>
									<td>3,25</td>
								</tr>
								<tr>
									<td>Z-escore AM - AP</td>
									<td>-0,07</td>
									<td>-1,89</td>
									<td>+1,93</td>
									<td>0,91</td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN2002">
								<p>CIA: comunicação interatrial; mm: milímetros; MI/CIA: diâmetro anel mitral/diâmetro comunicação interatrial; LL: laterolateral; AP: anteroposterior; CIA/septo: diâmetro comunicação interatrial/diâmetro septo interatrial; QP/QS: fluxo pulmonar/ fluxo sistêmico; AT: anel tricúspide; AM: anel mitral.</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
				<sec>
					<title>Associação e correlação entre variáveis</title>
					<p>Na <xref ref-type="table" rid="t3002">Tabela 3</xref> estão dispostas as comparações entre sinais clínicos e medidas ecocardiográficas. Não houve associação entre sexo e quaisquer variáveis estudadas, sejam clínicas ou ecocardiográficas.</p>
					<p>
						<table-wrap id="t3002">
							<label>Tabela 3</label>
							<caption>
								<title>– Comparação entre parâmetros clínicos e ecocardiográficos</title>
							</caption>
							<table frame="hsides" rules="groups">
								<colgroup>
									<col/>
									<col/>
									<col/>
									<col/>
									<col/>
									<col/>
									<col/>
								</colgroup>
								<thead>
									<tr>
										<th align="left" style="font-weight:normal"> </th>
										<th align="left" colspan="6">Valor-p</th>
									</tr>
									<tr>
										<th align="left">Parâmetro Clínico</th>
										<th align="left">MI/CIA – AP</th>
										<th align="left">MI/CIA-LL</th>
										<th align="left">CIA/septo</th>
										<th align="left">QP/QS</th>
										<th align="left">TAMANHO CIA ASCD*</th>
										<th align="left">Z-escore AT</th>
									</tr>
								</thead>
								<tbody>
									<tr>
										<td>Impulsões de VD</td>
										<td>0,028</td>
										<td>0,018</td>
										<td>0,15</td>
										<td>0,35</td>
										<td>0,025</td>
										<td>0,56</td>
									</tr>
									<tr>
										<td>Desdobramento de B2</td>
										<td>&lt; 0,001</td>
										<td>&lt; 0,001</td>
										<td>&lt; 0,001</td>
										<td>0,006</td>
										<td>&lt; 0,001</td>
										<td>0,12</td>
									</tr>
									<tr>
										<td>Sopro sistólico pulmonar</td>
										<td>0,015</td>
										<td>0,006</td>
										<td>0,022</td>
										<td>0,037</td>
										<td>0,002</td>
										<td>0,41</td>
									</tr>
									<tr>
										<td>Sopro diastólico tricúspide</td>
										<td>0,055</td>
										<td>0,045</td>
										<td>0,015</td>
										<td>0,016</td>
										<td>0,29</td>
										<td>0,019</td>
									</tr>
								</tbody>
							</table>
							<table-wrap-foot>
								<fn id="TFN3002">
									<p>* teste de Fisher, demais variáveis com análise pelo teste T de Student não pareado. MI/CIA: diâmetro anel mitral /diâmetro comunicação interatrial; AP: anteroposterior; LL: laterolateral; CIA/septo: diâmetro comunicação interatrial/diâmetro septo interatral; QP/QS: fluxo pulmonar/ fluxo sistêmico; ASCD: avaliação subjetiva de câmaras direitas; AT: anel tricúspide; VD: ventrículo direito; B2: segunda bulha.</p>
								</fn>
							</table-wrap-foot>
						</table-wrap>
					</p>
					<p>Com relação à classificação clínica da CIA, 12 foram consideras como pequenas, 18 médias e 5 grandes. A correlação entre a magnitude da CIA pela classificação clínica e os achados ecocardiográficos está sumarizada na <xref ref-type="table" rid="t4002">Tabela 4</xref>.</p>
					<p>
						<table-wrap id="t4002">
							<label>Tabela 4</label>
							<caption>
								<title>– Correlação entre tamanho da CIA pela classificação clínica e variáveis ecocardiográficas</title>
							</caption>
							<table frame="hsides" rules="groups">
								<colgroup>
									<col/>
									<col/>
									<col/>
								</colgroup>
								<thead>
									<tr>
										<th align="left">Variáveis ecocardiográficas</th>
										<th align="left">Coeficiente de Pearson</th>
										<th align="left">Valor-p</th>
									</tr>
								</thead>
								<tbody>
									<tr>
										<td>Tamanho CIA: avaliação subjetiva de câmaras direitas</td>
										<td>0,52</td>
										<td>0,001</td>
									</tr>
									<tr>
										<td>Tamanho CIA: avaliação Z-escore AT</td>
										<td>0,26</td>
										<td>0,13</td>
									</tr>
									<tr>
										<td>Z-escore AT anteroposterior</td>
										<td>0,34</td>
										<td>0,045</td>
									</tr>
									<tr>
										<td>Z-escore AT laterolateral</td>
										<td>0,34</td>
										<td>0,048</td>
									</tr>
									<tr>
										<td>CIA/septo</td>
										<td>0,56</td>
										<td>&lt;0,001</td>
									</tr>
									<tr>
										<td>QP/QS</td>
										<td>0,62</td>
										<td>0,002</td>
									</tr>
									<tr>
										<td>MI/CIA anteroposterior</td>
										<td>-0,58</td>
										<td>&lt;0,001</td>
									</tr>
									<tr>
										<td>MI/CIA laterolateral</td>
										<td>-0,61</td>
										<td>&lt;0,001</td>
									</tr>
								</tbody>
							</table>
							<table-wrap-foot>
								<fn id="TFN4002">
									<p>CIA: comunicação interatrial; AT: anel tricúspide; CIA/septo: diâmetro comunicação interatrial/diâmetro septo interatrial; QP/QS: fluxo pulmonar/fluxo sistêmico; MI/CIA: diâmetro anel mitral /diâmetro comunicação interatrial.</p>
								</fn>
							</table-wrap-foot>
						</table-wrap>
					</p>
					<p>As relações de diâmetros MI/CIA apresentaram forte correlação inversa com a medida CIA/septo. O coeficiente de Pearson com as medidas anteroposterior e laterolateral foram de -0,80 (p &lt; 0,001). Houve forte correlação inversa também com a medida QP/QS, com coeficiente de Pearson de -0,71 (p &lt; 0,001) para a medida anteroposterior e de -0,76 (p &lt; 0,001) para a medida laterolateral.</p>
					<p>A relação entre os diâmetros CIA/septo apresentou forte correlação com a relação QP/QS com coeficiente de Pearson de 0,63 (p = 0,001).</p>
					<p>Com relação ao tamanho do VD à avaliação subjetiva, 17 participantes apresentaram VD maior que VE, 10 apresentaram tamanho menor e 8 apresentaram câmaras de tamanhos equivalentes. À avaliação do AD, 20 participantes apresentaram AD maior que AE, 8 apresentaram tamanho menor e 7 apresentaram câmaras de tamanhos equivalentes. A comparação e a correlação entre o grau de dilatação de câmaras direitas e as variáveis ecocardiográficas estão demonstradas nas <xref ref-type="table" rid="t5002">Tabela 5</xref> e <xref ref-type="table" rid="t6002">6</xref>.</p>
					<p>
						<table-wrap id="t5002">
							<label>Tabela 5</label>
							<caption>
								<title>– Comparação entre grau de dilatação de câmaras direitas segundo avaliação subjetiva e variáveis ecocardiográficas</title>
							</caption>
							<table frame="hsides" rules="groups">
								<colgroup>
									<col/>
									<col/>
									<col/>
									<col/>
									<col/>
									<col/>
									<col/>
									<col/>
								</colgroup>
								<thead>
									<tr>
										<th align="left" style="font-weight:normal"> </th>
										<th align="left" colspan="6">Grau de dilatação de câmaras direitas</th>
										<th align="left" style="font-weight:normal"> </th>
									</tr>
									<tr>
										<th align="left">Variáveis</th>
										<th align="left">Leve</th>
										<th align="left">Desvio-padrão</th>
										<th align="left">Moderada</th>
										<th align="left">Desvio-padrão</th>
										<th align="left">Importante</th>
										<th align="left">Desvio-padrão</th>
										<th align="left">Valor-p (ANOVA)</th>
									</tr>
								</thead>
								<tbody>
									<tr>
										<td>Diâmetro CIA (mm)</td>
										<td>5,15</td>
										<td>2,27</td>
										<td>11,8</td>
										<td>6,12</td>
										<td>17,37</td>
										<td>8,01</td>
										<td>0,001</td>
									</tr>
									<tr>
										<td>MI/CIA-AP</td>
										<td>4,07</td>
										<td>1,69</td>
										<td>1,78</td>
										<td>0,84</td>
										<td>1,24</td>
										<td>0,48</td>
										<td>&lt; 0,001</td>
									</tr>
									<tr>
										<td>MI/CIA-LL</td>
										<td>4,15</td>
										<td>1,58</td>
										<td>1,86</td>
										<td>0,85</td>
										<td>1,25</td>
										<td>0,52</td>
										<td>&lt; 0,001</td>
									</tr>
									<tr>
										<td>CIA/septo</td>
										<td>0,13</td>
										<td>0,06</td>
										<td>0,29</td>
										<td>0,14</td>
										<td>0,36</td>
										<td>0,13</td>
										<td>&lt; 0,001</td>
									</tr>
									<tr>
										<td>QP/QS</td>
										<td>1,19</td>
										<td>0,10</td>
										<td>2,45</td>
										<td>0,93</td>
										<td>3,05</td>
										<td>0,84</td>
										<td>0,007</td>
									</tr>
									<tr>
										<td>Z-escore AT-AP</td>
										<td>-0,17</td>
										<td>0,00</td>
										<td>+1,00</td>
										<td>1,28</td>
										<td>+1,66</td>
										<td>1,04</td>
										<td>0,001</td>
									</tr>
									<tr>
										<td>Z-escore AT-LL</td>
										<td>-0,04</td>
										<td>1,30</td>
										<td>+1,17</td>
										<td>0,75</td>
										<td>+2,06</td>
										<td>1,81</td>
										<td>0,01</td>
									</tr>
								</tbody>
							</table>
							<table-wrap-foot>
								<fn id="TFN5002">
									<p>CIA: comunicação interatrial; mm: milímetros; AD: átrio direito; VD: ventrículo direito; MI/CIA: diâmetro anel mitral /diâmetro comunicação interatrial; AP: anteroposterior; LL: laterolateral; CIA/septo: diâmetro comunicação interatrial/diâmetro septo interatrial; QP/QS: fluxo pulmonar/ fluxo sistêmico; AT: anel tricúspide.</p>
								</fn>
							</table-wrap-foot>
						</table-wrap>
					</p>
					<p>
						<table-wrap id="t6002">
							<label>Tabela 6</label>
							<caption>
								<title>– Correlação entre grau de dilatação de câmaras direitas segundo avaliação subjetiva e variáveis ecocardiográficas</title>
							</caption>
							<table frame="hsides" rules="groups">
								<colgroup>
									<col/>
									<col/>
									<col/>
								</colgroup>
								<thead>
									<tr>
										<th align="left">Variáveis</th>
										<th align="left">Coeficiente de Pearson</th>
										<th align="left">Valor-p</th>
									</tr>
								</thead>
								<tbody>
									<tr>
										<td>Diâmetro CIA (mm)</td>
										<td>0,61/0,66 AD/VD</td>
										<td>&lt;0,001 AD/VD</td>
									</tr>
									<tr>
										<td>MI/CIA-AP</td>
										<td>-0,75</td>
										<td>&lt;0,001</td>
									</tr>
									<tr>
										<td>MI/CIA-LL</td>
										<td>-0,77</td>
										<td>&lt;0,001</td>
									</tr>
									<tr>
										<td>CIA/septo</td>
										<td>0,62</td>
										<td>&lt;0,001</td>
									</tr>
									<tr>
										<td>QP/QS</td>
										<td>0,61</td>
										<td>0,002</td>
									</tr>
									<tr>
										<td>Z-escore AT-AP</td>
										<td>0,58</td>
										<td>&lt;0,001</td>
									</tr>
									<tr>
										<td>Z-escore AT-LL</td>
										<td>0,50</td>
										<td>0,002</td>
									</tr>
								</tbody>
							</table>
							<table-wrap-foot>
								<fn id="TFN6002">
									<p>CIA: comunicação interatrial; mm: milímetros; AD: átrio direito; VD: ventrículo direito; MI/CIA: diâmetro anel mitral /diâmetro comunicação interatrial; AP: anteroposterior; LL: laterolateral; CIA/septo: diâmetro comunicação interatrial/diâmetro septo interatrial; QP/QS: fluxo pulmonar/ fluxo sistêmico; AT: anel tricúspide.</p>
								</fn>
							</table-wrap-foot>
						</table-wrap>
					</p>
					<p>Considerando-se o Z-escore do AT para classificação do tamanho das CIAs, foram encontradas 25 pequenas, 5 médias e 5 grandes. Tal classificação não apresentou associação com a classificação clínica da CIA nem com a classificação ecocardiográfica, baseada na avaliação subjetiva das câmaras direitas.</p>
				</sec>
				<sec>
					<title>Curva de operação característica</title>
					<p>Aplicando-se a curva de operação característica, considerando-se a variável estável classificação do Defeito do Septo Atrial segundo tamanho subjetivo de câmaras direitas, foi obtida a área abaixo da curva de 0,85 para a relação CIA/septo. A curva e os dados com o valor-p e os intervalos de confiança de 95% estão demonstrados na <xref ref-type="fig" rid="f03002">Figura 2</xref>. O melhor ponto de corte foi de 0,27, com sensibilidade de 85% e especificidade de 86,7% para diagnóstico de CIA grande. O VPP foi de 76% e o VPN foi de 85,2%. A razão de verossimilhança positiva foi de 6,39.</p>
					<p>
						<fig id="f03002">
							<label>Figura 2</label>
							<caption>
								<title>– Curva de operação característica para a relação CIA/septo considerando-se a variável estável classificação do defeito do septo atrial segundo tamanho subjetivo de câmaras direitas. ROC: curva de operação característica.</title>
							</caption>
							<graphic xlink:href="2675-312x-abcimg-38-2-e20240089-gf03-pt.tif"/>
						</fig>
					</p>
					<p>Quanto à variável classificação da CIA segundo tamanho subjetivo de câmaras direitas, foi obtida a área abaixo da curva de 0,14 para a relação MI/CIA.</p>
				</sec>
			</sec>
			<sec sec-type="discussion">
				<title>Discussão</title>
				<p>Os principais achados deste estudo foram a forte correlação inversa entre a relação MI/CIA e a classificação clínica da CIA, e a probabilidade de 6,39 de diagnóstico de CIA grande por meio da relação CIA/septo superior a 0,27, segundo o tamanho subjetivo de câmaras direitas conforme sumarizado na <xref ref-type="fig" rid="f01002">figura central</xref>.</p>
				<p>A forma universal usada por cardiologistas para classificar o tamanho da CIA é baseada em vários fatores subjetivos clínico-ecocardiográficos. São avaliados a presença de sintomas, as alterações ao exame físico e os achados do exame ecocardiográfico. Considerando-se que na faixa etária pediátrica há grande variabilidade de valores de superfície corporal, a medida de diâmetro isolada da CIA não é um parâmetro adequado para quantificar a magnitude da lesão. Para essa avaliação, são levados em consideração outros parâmetros, como a relação QP/QS,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> a relação de diâmetros CIA/septo interatrial e avaliação do grau de dilatação de câmaras direitas.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup></p>
				<p>Na época do estudo, existia apenas um trabalho<sup><xref ref-type="bibr" rid="B13">13</xref></sup> que apresentava valores de normalidade para as medidas lineares e de área de AD e VD, conforme indicadas pela diretriz de medidas de ecocardiograma<sup><xref ref-type="bibr" rid="B7">7</xref></sup> para a população pediátrica. Tal estudo teve como limitações ter sido unicêntrico, realizado apenas com população caucasiana, com idades de 0 a 3 anos. Dessa forma, o estudo não pôde ser incorporado à prática clínica pois não abrangeu todas as faixas etárias pediátricas. Desde então, surgiram duas novas publicações<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B15">15</xref></sup> de valores referências em pediatria. Rajagopal et al.<bold>,</bold> descreveram medidas de área de AD, porém tratou-se de estudo unicêntrico e retrospectivo, cujos resultados ainda não foram incorporados à prática clínica.<sup><xref ref-type="bibr" rid="B14">14</xref></sup>Gokhroo et al<bold>.,</bold> apresentaram valores de referência para medidas, conforme recomendado pela diretriz, porém o estudo se limitou à faixa etária de 5 a 15 anos.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> Sendo assim, a avaliação de dilatação de câmaras direitas é feita rotineiramente de forma subjetiva, comparando-se visualmente ao modo bidimensional a área das câmaras direitas com a das câmaras esquerdas no corte apical quatro câmaras. A relação QP/QS apesar de ser uma medida objetiva, é muito passível de erros e de execução laboriosa.<sup><xref ref-type="bibr" rid="B16">16</xref></sup></p>
				<p>Rao et al<bold>.,</bold> apresentaram o método de classificação da magnitude do <bold>shunt</bold> residual pela CIA após fechamento percutâneo levando em consideração os parâmetros de diâmetro do fluxo maior que 2 mm e medidas de VD com percentil &gt; 95% mas não propuseram classificação da magnitude da lesão em si.<sup><xref ref-type="bibr" rid="B17">17</xref></sup></p>
				<p>Não existem na literatura trabalhos que avaliem a relação CIA/septo para classificação da magnitude da CIA. Lin et al<bold>.,</bold> utilizaram as medidas do Septo Interatrial e da CIA ao modo bidimensional e ao Color com o uso da inteligência artificial em população com idade média de 3 anos, e demonstrou boa acurácia em detectar os defeitos e os casos passíveis de fechamento percutâneo da lesão pelas medidas das bordas livres do septo, entretanto esse estudo não avaliou o grau da repercussão hemodinâmica, classificação do tamanho da lesão nem a necessidade de tratamento.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> As medidas escolhidas no presente estudo foram as relações MI/CIA e CIA/septo como forma de indexar a medida da CIA a uma estrutura cardíaca e que apresentasse medida de fácil execução. A medida da CIA foi realizada utilizando-se o maior diâmetro linear.</p>
				<p>Considerando-se que as lesões podem ser assimétricas, as medidas de diâmetro realizadas podem não refletir necessariamente o maior diâmetro da lesão. A medida mais fidedigna seria o cálculo de área da CIA, que é pelos exames ecocardiográfico 3D e ressonância magnética, porém são exames pouco disponíveis na prática clínica.<sup><xref ref-type="bibr" rid="B19">19</xref>,<xref ref-type="bibr" rid="B20">20</xref></sup> Dessa maneira, para evitar maiores vieses, as medidas do diâmetro foram realizadas em imagens com boa qualidade técnica, utilizando o mesmo corte subcostal em todos os participantes, sendo este muito parecido com o corte esôfago médio bicaval do exame ecocardiográfico transesofágico, o qual é usado para guiar o fechamento percutâneo da CIA com prótese.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> Boon et al<bold>.,</bold> demonstraram que o exame ecocardiográfico 2D é um método confiável para a medida do diâmetro da CIA, especialmente nos casos em que o septo é firme, correspondendo a 85% dos casos de CIA <bold>ostium secundum.</bold><sup><xref ref-type="bibr" rid="B21">21</xref></sup></p>
				<p>A medida MI/CIA apresentou forte correlação inversa com a classificação clínica da CIA e com a classificação pela avaliação subjetiva de câmaras direitas. Apesar disso, não foi possível delimitar pontos de corte dessa variável para classificação do tamanho do defeito. Embora seja intuitivo imaginar que quanto menor a relação, maior o déficit de enchimento do VE e de desenvolvimento do anel mitral, pode-se especular que tal relação não seja tão linear com o tamanho da CIA a ponto de permitir qualificação assertiva de tamanho.</p>
				<p>A medida CIA/septo apresentou moderada correlação com a classificação clínica da CIA e forte correlação com a classificação pela avaliação subjetiva de câmaras direitas. Não foi possível delimitar pontos de corte para classificação da magnitude da CIA considerando-se a sua classificação clínica. Tal achado talvez possa ser explicado pelo pequeno número de CIAs grandes classificadas pelo método clínico. Foi encontrado ponto de corte para a relação CIA/septo de 0,27 para identificação das CIAs grandes em comparação com a avaliação subjetiva do tamanho das câmaras direitas. O mesmo não foi possível para a CIAs médias, talvez também pelo pequeno número de participantes com CIA média segundo a classificação pela avaliação subjetiva de câmaras direitas.</p>
				<p>No que se refere à relação QP/QS, é um dos parâmetros utilizados nas diretrizes para indicação de fechamento da CIA na população adulta.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> Apresentou forte correlação com as medidas MI/CIA, CIA/septo e com a classificação clínica e ecocardiográfica da CIA pela avaliação subjetiva de câmaras direitas. Pode apresentar grande variabilidade<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup>devido ao próprio modo de cálculo da relação, pois são necessárias quatro medidas para sua realização, sendo elas o raio e a integral velocidade-tempo de via de saída de VD e VE. O erro em qualquer uma das quatro medidas pode alterar o valor final da relação. Além disso, a medida do raio é elevada ao quadrado, o que faz com que um erro na medida do raio se eleve ao quadrado no cálculo.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> Faherty et al., correlacionaram os valores de cálculo de QP/QS ao ecocardiograma com aqueles obtidos pela oximetria ao cateterismo em pacientes com CIA <bold>ostium secundum</bold> hemodinamicamente significativos e encontraram fraca correlação entre os métodos, sendo que o método ecocardiográfico tende a superestimar os valores obtidos à oximetria.<sup><xref ref-type="bibr" rid="B23">23</xref></sup></p>
				<p>Na prática clínica, é comum a repetição da medida quando o ecocardiografista encontra valor que julgue não ser compatível com os demais achados. Sendo assim, o modo de fazer tal medida apresenta um viés subjetivo. No protocolo de coleta dos dados do estudo, não foi limitado o número de repetições de medidas para o cálculo da relação QP/QS, ficando a critério do ecocardiografista escolher o valor do cálculo que julgasse ser mais fidedigno. Esse viés de subjetividade pode ter contribuído para o achado de uma forte correlação dessa medida com as demais variáveis estudadas.</p>
				<p>A medida de Z-escore de AT apresentou fraca correlação com a classificação clínica da CIA e moderada correlação com a classificação baseada na avaliação subjetiva de câmaras direitas. Uma explicação para tais achados pode ser a falta de normalização dos valores de referência de Z-escore para medidas de AT na literatura. Apesar da padronização do modo de medida dos estudos mais recentes e de seu maior número amostral se comparados com estudos mais antigos,<sup><xref ref-type="bibr" rid="B24">24</xref>-<xref ref-type="bibr" rid="B26">26</xref></sup> ainda existem diferenças entre os nomogramas, que resultam em Z-escores muito discordantes entre si. Os estudos apresentam diferenças entre si como fórmula de superfície corporal utilizada, diferenciação ou não entre os sexos, faixa de idade utilizada, variabilidade intraobservador e interobservador.<sup><xref ref-type="bibr" rid="B27">27</xref></sup> Snyder et al., demonstraram não haver uma relação linear forte entre o volume de VD à ressonância magnética cardíaca e o Z-escore da valva tricúspide ao exame ecocardiográfico em pacientes em pós-operatório tardio de Tetralogia de Fallot. Entre os pacientes com dilatação de VD à ressonância, a medida de Z-escore do AT ao exame ecocardiográfico apresentou uma sensibilidade de 45% para identificar dilatação, com Z-escore &gt; +2.<sup><xref ref-type="bibr" rid="B28">28</xref></sup> No presente estudo, foi observado Z-escore de diâmetro de valva tricúspide na faixa de normalidade apesar de VD dilatado à avaliação bidimensional em comparação ao VE em alguns participantes.</p>
				<p>A classificação da magnitude da CIA pelo valor de Z-escore do AT conforme descrita na metodologia não se associou a nenhum dos parâmetros pesquisados ao exame físico e consequentemente à classificação clínica da CIA, bem como não se associou à classificação da CIA segundo avaliação subjetiva de câmaras direitas. Além da variabilidade de valores de normalidade de Z-escore na população pediátrica já citada, deve-se considerar a escolha da faixa de Z-escore utilizada para a classificação. No estudo, não foram comparadas diferentes faixas de Z-escore e avaliada a associação de cada uma delas aos outros métodos de classificação da magnitude da CIA.</p>
				<p>Muitos dos resultados encontrados no estudo estão de acordo com os dados de literatura. Dentre eles, a frequência dos achados ao exame físico e proporção entre os sexos.</p>
				<p>A frequência foi maior no sexo feminino, numa proporção de 2,2:1, muito próxima da descrita na literatura de 2:1.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Os percentuais encontrados de desdobramento amplo e fixo de B2, sopro sistólico em foco pulmonar e sopro diastólico em foco tricúspide foram 66%, 83% e 15%, respectivamente, similares aos valores descritos na literatura de 66%, 90% e 12%, respectivamente.<sup><xref ref-type="bibr" rid="B29">29</xref></sup> Com relação a impulsões de VD, a presença e intensidade de tal achado depende muito do biotipo do paciente.</p>
				<p>O tipo de CIA mais frequentemente encontrado é o <bold>ostium secundum</bold>, responsável por cerca de 85% dos casos.<sup><xref ref-type="bibr" rid="B30">30</xref></sup> No estudo, foi o único tipo encontrado, achado esse que pode ser explicado pelo pequeno tamanho da amostra.</p>
				<p>Dentre os parâmetros pesquisados pelo exame físico, todos se associaram à classificação subjetiva de câmaras direitas, exceto o sopro diastólico em foco tricúspide. Tal fato pode ser explicado pela baixa sensibilidade desse parâmetro para o diagnóstico da CIA.<sup><xref ref-type="bibr" rid="B29">29</xref></sup></p>
				<sec>
					<title>Limitações</title>
					<p>Este estudo apresenta algumas limitações por ser unicêntrico, transversal, com pequeno tamanho amostral e grande desvio-padrão de idade. Além disso, as variabilidades intraobservador e interobservador referentes ao método clínico e ao exame ecocardiográfico não puderam ser avaliadas, porém houve treinamento prévio da equipe com relação ao protocolo de medidas. Não foi utilizado teste post hoc para se verificar as diferenças significativas entre as medidas dos parâmetros ecocardiográficos e a avaliação subjetiva da dilatação das câmaras direitas.</p>
				</sec>
			</sec>
			<sec sec-type="conclusions">
				<title>Conclusões</title>
				<p>As medidas MI/CIA e CIA/septo apresentaram associação com a classificação da CIA quanto a sua magnitude com relação aos parâmetros clínicos e avaliação subjetiva do tamanho de câmaras direitas ao ecocardiograma. A medida da relação CIA/septo acima de 0,27 mostrou ser útil na identificação de CIA grande com base na dilatação subjetiva de câmaras direitas, o que não foi encontrado nas CIAs pequena e média. Não foi possível delimitar pontos de corte da medida MI/CIA para classificar a CIA quanto a sua magnitude. A medida de Z-escore do AT não foi bom parâmetro para classificar a magnitude da CIA.</p>
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					<label>Vinculação Acadêmica:</label>
					<p> Este artigo é parte de dissertação de Mestrado de Lívia de Castro Ribeiro pela Universidade Federal de Minas Gerais.</p>
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					<label>Aprovação Ética e Consentimento Informado:</label>
					<p> Este estudo foi aprovado pelo Comitê de Ética da UFMG sob o número de protocolo 53353116.3.0000.5149. 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>
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				<fn fn-type="financial-disclosure">
					<label>Fontes de Financiamento:</label>
					<p>O presente estudo não teve fontes de financiamento externas.</p>
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