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<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "https://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<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.20240093i</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Original Article</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Impact of Valvular Event Time Assessment Methods on Myocardial Work Calculation by Echocardiography</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-7900-6506</contrib-id>
					<name>
						<surname>Pereira</surname>
						<given-names>Marcio Mendes</given-names>
					</name>
					<role>Conception and design of the research</role>
					<role>writing of the manuscript</role>
					<role>acquisition of data and statistical analysis</role>
					<role>analysis and interpretation of the data</role>
					<role>critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="corresp" rid="c1"/>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0003-3799-8057</contrib-id>
					<name>
						<surname>Monteiro</surname>
						<given-names>Francisco das Chagas</given-names>
						<suffix>Júnior</suffix>
					</name>
					<role>Conception and design of the research</role>
					<role>writing of the manuscript</role>
					<role>critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0004-4443-0552</contrib-id>
					<name>
						<surname>Yamamura</surname>
						<given-names>Sayuri</given-names>
					</name>
					<role>Conception and design of the research</role>
					<role>writing of the manuscript</role>
					<role>analysis and interpretation of the data</role>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<aff id="aff1">
					<label>1</label>
					<institution content-type="orgname">UDI Hospital</institution>
					<addr-line>
						<named-content content-type="city">São Luis</named-content>
						<named-content content-type="state">MA</named-content>
					</addr-line>
					<country country="BR">Brazil</country>
					<institution content-type="original">UDI Hospital, São Luis, MA – Brazil</institution>
				</aff>
				<aff id="aff2">
					<label>2</label>
					<institution content-type="orgname">Universidade Federal do Maranhão</institution>
					<addr-line>
						<named-content content-type="city">São Luis</named-content>
						<named-content content-type="state">MA</named-content>
					</addr-line>
					<country country="BR">Brazil</country>
					<institution content-type="original">Universidade Federal do Maranhão, São Luis, MA – Brazil</institution>
				</aff>
			</contrib-group>
			<author-notes>
				<corresp id="c1">
					<label>Mailing Address:</label><bold>Marcio Mendes Pereira</bold> • UDI Hospital. Av. Prof. Carlos Cunha, 2000. Postal code: <postal-code>65076-820</postal-code>. Jaracati, São Luis, MA – Brazil E-mail: <email>marciomp50@hotmail.com</email>
				</corresp>
				<fn fn-type="conflict">
					<label>Potential Conflict of Interest</label>
					<p>No potential conflict of interest relevant to this article was reported.</p>
				</fn>
				<fn fn-type="edited-by">
					<label>Editor responsible for the review:</label>
					<p>Marcelo Tavares</p>
				</fn>
			</author-notes>
			<pub-date date-type="pub" publication-format="electronic">
				<day>05</day>
				<month>12</month>
				<year>2024</year>
			</pub-date>
			<pub-date date-type="collection" publication-format="electronic">
				<year>2024</year>
			</pub-date>
			<volume>37</volume>
			<issue>4</issue>
			<elocation-id>e20240093</elocation-id>
			<history>
				<date date-type="received">
					<day>07</day>
					<month>10</month>
					<year>2024</year>
				</date>
				<date date-type="rev-recd">
					<day>09</day>
					<month>10</month>
					<year>2024</year>
				</date>
				<date date-type="accepted">
					<day>10</day>
					<month>10</month>
					<year>2024</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>Left ventricular ejection fraction (LVEF) is the traditional parameter for assessing cardiac function, but it has limitations in the early detection of dysfunction. Global Longitudinal Strain (GLS) and myocardial work (MW) are promising alternatives, the latter being less influenced by load conditions. The calculation of MW depends on valvular event times (VET), obtained by methods that may generate divergent results.</p>
				</sec>
				<sec>
					<title>Objectives:</title>
					<p>To compare the impact of different methods of VET measurement – visual analysis (VA), tissue Doppler imaging (TDI) and pulsed Doppler (PD) – on global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE).</p>
				</sec>
				<sec>
					<title>Method:</title>
					<p>Cross-sectional clinical study with 35 healthy patients who underwent echocardiography between October 2022 and March 2023. MW was assessed using the EchoPAC software, with VET measurement by VA, TDI and DP. The results were analyzed by ANOVA and Friedman tests, followed by post-hoc analyses with a significance level of 5%.</p>
				</sec>
				<sec>
					<title>Results:</title>
					<p>GWI showed significant variation between the VET measurement methods, being lower by AV compared to TDI and DP (p&lt;0.001). The GCW, GWW and GWE indexes did not demonstrate statistically significant differences between the methods.</p>
				</sec>
				<sec>
					<title>Conclusions:</title>
					<p>The VET measurement method significantly impacts the GWI, but does not affect the other MW indexes.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="en">
				<title>Keywords</title>
				<kwd>Echocardiography</kwd>
				<kwd>Left Ventricular Dysfunction</kwd>
				<kwd>Ventricular Function</kwd>
			</kwd-group>
			<counts>
				<fig-count count="10"/>
				<table-count count="8"/>
				<equation-count count="0"/>
				<ref-count count="9"/>
			</counts>
		</article-meta>
	</front>
	<body>
		<sec sec-type="intro">
			<title>Introduction</title>
			<p>Left ventricular ejection fraction (LVEF) has been widely used in the assessment of systolic function in several clinical conditions, especially cardiac diseases. However, studies have demonstrated that LVEF has limitations, particularly in the early detection of cardiac dysfunction in patients with preserved ejection fraction but with subclinical impairment. In this context, new echocardiographic techniques, like the global longitudinal strain (GLS) have gained importance, providing a more sensitive assessment of myocardial deformation.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup></p>
			<p>More recently, the introduction of the concept of myocardial work (MW) has enabled a more comprehensive evaluation of cardiac function, considering the interaction between myocardial strain and afterload during cardiac cycle. In contrast to GLS, MW is less influenced by preload and afterload conditions, which may provide a more robust estimate of myocardial function.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup></p>
			<p>For MW calculation, it is essential to precisely estimate valvular event times (VETs), particularly events related to the aortic valve opening and closure. The times may be obtained using different methods, including visual analysis (VA), tissue doppler imaging (TDI) and pulsed Doppler (PD) ultrasound. However, there is no consensus on the most accurate method, and implications on MW indexes – global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) – are still little explored.<sup><xref ref-type="bibr" rid="B5">5</xref>-<xref ref-type="bibr" rid="B8">8</xref></sup></p>
			<p>The aim of the present study was to compare the methods used for VET estimation for differences in determining MW.</p>
		</sec>
		<sec sec-type="methods">
			<title>Methods</title>
			<p>This was a cross-sectional study with 35 patients, conducted in a private hospital in Sao Luis, state of Maranhão, Brazil, between October 2022 and March 2023. Patients aged 18 years or older, without comorbidities underwent echocardiography. The echocardiographic studies were conducted following the American Society of Echocardiography (ASE) recommendations, with two-dimensional images recorded during three cardiac cycles, synchronized with the QRS complex, for offline analysis using the EchoPAC software (version 202, GE Vingmed Ultrasound). LVEF was determined by the Simpson method.</p>
			<fig id="f9">
				<caption>
					<title>Calculation of MW. Estimation of VET by VA, pulsed wave Doppler of mitral inflow and LV outflow and tissue doppler of the mitral annulus tissue. Using automated function imaging, the GLS is generated through the apical 2, 3 and 4-chamber views. GWI, calculated using the event markers obtained by VA is lower than GWI values obtained by tissue Doppler and PD. LVP: left ventricular pressure; GWI: global work index</title>
				</caption>
				<graphic xlink:href="2675-312X-abcimg-37-04-e20240093-gf01.tif"/>
			</fig>
			<p>The GWI was estimated by calculating the segmental shortening rate by differentiation of the strain tracing and multiplying by instantaneous left ventricular (LV) pressure. This instantaneous measure was integrated over time to measure MW as a function of time during systole (time interval from mitral valve closure to mitral valve opening). During LV ejection, segments were analyzed for GWW and/or GCW, with global values determined as means of all segmental values and displayed on the LV pressure-strain loop diagram.</p>
			<p>The main parameters calculated were the following: GWI (mmHg%), area within the LV pressure curve; GCW (mmHg%), estimated work performed by the LV segments; GWW (mmHg%), estimated negative work done by the LV segments; GWE (mmHg%) (defined as the ratio between GCW and the sum of GCW and GWW.</p>
			<p>Categorical variables were expressed as absolute and relative frequencies, and continuous variables as mean and standard deviations, depending on data distribution. Normality of data distribution was assessed by the Shapiro-Wilk test (p&lt;0.05).</p>
			<p>Sample size was calculated to detect a difference of 123 mmHg% in GWI between the methods, with a power of 90% and level of significance of 5%. Comparisons of means were made by ANOVA for parametric data and the Friedman test for nonparametric data. Post-hoc tests, like pairwise comparisons of the marginal linear predictions and the Bonferroni test were applied to detect significant differences. The statistical analysis was performed using the Stata® Intercooled test, version 18.0.</p>
			<p>The study was approved by the ethics committee of Sao Domingos hospital and maternity hospital (CAAE 71514222.1.0000.5085).</p>
		</sec>
		<sec sec-type="results">
			<title>Results</title>
			<p>Mean age of patients was 39.9 years (18-60 years), and most of them were men (57.1%). Clinical and echocardiographic parameters of participants are summarized in <xref ref-type="table" rid="t1">Table 1</xref>. Averages of echocardiographic measurements were within normal range.</p>
			<table-wrap id="t1">
				<label>Table 1</label>
				<caption>
					<title>General and echocardiographic characteristics of the study patients</title>
				</caption>
				<table frame="hsides" rules="none">
					<colgroup width="49%">
						<col width="1%"/>
						<col/>
						<col/>
					</colgroup>
					<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
						<tr style="background-color:#C58874">
							<th align="left" colspan="2" valign="middle">Variables</th>
							<th align="center" valign="middle">TOTAL (n = 35)</th>
						</tr>
					</thead>
					<tbody style="border-bottom: thin solid; border-color: #000000">
						<tr style="background-color:#E7CCBF">
							<td align="left" colspan="2" valign="middle"><bold>Clinical profile</bold></td>
							<td align="center" valign="middle"/>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" colspan="2" valign="middle">Age</td>
							<td align="center" valign="middle">38.88 (18; 60)</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" colspan="2" valign="middle">Sex (%)</td>
							<td align="center" valign="middle"/>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle"/>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">57.14</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle"/>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">42.86</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" colspan="2" valign="middle">Body surface (cm²)</td>
							<td align="center" valign="middle">1.87 ± 0.21</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" colspan="2" valign="middle">Height (m)</td>
							<td align="center" valign="middle">1.68 (1.50; 1.88)</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" colspan="2" valign="middle">Weight (kg):</td>
							<td align="center" valign="middle">77 (51; 124)</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" colspan="2" valign="middle">Systolic blood pressure (mmHg)</td>
							<td align="center" valign="middle">114 ± 9</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" colspan="2" valign="middle">Diastolic blood pressure (mmHg)</td>
							<td align="center" valign="middle">72 ± 7</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" colspan="2" valign="middle">Heart rate (bpm)</td>
							<td align="center" valign="middle">67 (47; 94)</td>
						</tr>
						<tr>
							<td align="left" colspan="2" valign="middle"><bold>Echocardiographic data</bold></td>
							<td align="center" valign="middle"/>
						</tr>
						<tr>
							<td align="left" colspan="2" valign="middle">End-diastolic diameter (mm)</td>
							<td align="center" valign="middle">4.84 ± 0.44</td>
						</tr>
						<tr>
							<td align="left" colspan="2" valign="middle">End-systolic diameter (mm)</td>
							<td align="center" valign="middle">2.98 ± 0.35</td>
						</tr>
						<tr>
							<td align="left" colspan="2" valign="middle">Septal thickness (mm):</td>
							<td align="center" valign="middle">0.82 ± 0.08</td>
						</tr>
						<tr>
							<td align="left" colspan="2" valign="middle">End-diastolic volume (mmHg):</td>
							<td align="center" valign="middle">90 ± 25</td>
						</tr>
						<tr>
							<td align="left" colspan="2" valign="middle">End-systolic volume (mmHg)</td>
							<td align="center" valign="middle">32 ± 12</td>
						</tr>
						<tr>
							<td align="left" colspan="2" valign="middle">Left atrial volume (mmHg)</td>
							<td align="center" valign="middle">24 ± 4</td>
						</tr>
						<tr>
							<td align="left" colspan="2" valign="middle">Ejection fraction (mmHg)</td>
							<td align="center" valign="middle">65 ± 3</td>
						</tr>
						<tr>
							<td align="left" colspan="2" valign="middle">LV mass index, (g/m²)</td>
							<td align="center" valign="middle">71 (48; 95.9)</td>
						</tr>
						<tr>
							<td align="left" colspan="2" valign="middle">Frame rate, (frames/s)</td>
							<td align="center" valign="middle">73 ± 52</td>
						</tr>
						<tr>
							<td align="left" colspan="2" valign="middle">GLS (%)</td>
							<td align="center" valign="middle">19 ± 1.8</td>
						</tr>
					</tbody>
				</table>
				<table-wrap-foot>
					<fn id="TFN1">
						<p>GLS: Global Longitudinal Strain</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
			<p>
				<xref ref-type="table" rid="t2">Table 2</xref> describes the comparisons between MW indexes by the method used for VET estimation. The values obtained by VA were significantly different (p&lt;0.001) than the Doppler (TDI and PD)-derived measurements. For example, mean GWI by VA was significantly lower than GWI estimated by TDI or PD. However, no significant differences were observed between the other myocardial indexes (<xref ref-type="table" rid="t2">Tables 2</xref> and <xref ref-type="table" rid="t3">3</xref>). These results were displayed in a Bland-Altman plot for a visual representation of the degree of agreement between the values obtained by different VET estimation methods. <xref ref-type="fig" rid="f1">Figure 1</xref> shows a more scattered distribution of points is observed in the plots A and B, indicating a lower degree of agreement between the values. <xref ref-type="fig" rid="f2">Figures 2</xref>, <xref ref-type="fig" rid="f3">3</xref> and <xref ref-type="fig" rid="f4">4</xref> corroborate the lack of statistical differences between the MW indexes calculated by different methods.</p>
			<table-wrap id="t2">
				<label>Table 2</label>
				<caption>
					<title>Comparison of the MW indexes according to the method applied for valvular event time estimation</title>
				</caption>
				<table frame="hsides" rules="none">
					<colgroup width="20%">
						<col/>
						<col/>
						<col/>
						<col/>
						<col/>
					</colgroup>
					<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
						<tr style="background-color:#C58874">
							<th align="left" valign="top">Myocardial indexes</th>
							<th align="center" valign="middle">VA</th>
							<th align="center" valign="middle">TDI</th>
							<th align="center" valign="middle">Pulsed-Doppler</th>
							<th align="center" valign="middle">p</th>
						</tr>
					</thead>
					<tbody style="border-bottom: thin solid; border-color: #000000">
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle">GWI, mmHg%</td>
							<td align="center" valign="middle">1748 ± 258</td>
							<td align="center" valign="middle">1910 ± 264</td>
							<td align="center" valign="middle">2098 ± 279</td>
							<td align="center" valign="middle">&lt;0,001<xref ref-type="table-fn" rid="TFN2">*</xref>
							</td>
						</tr>
						<tr>
							<td align="left" valign="middle">TMCG, mmHg%</td>
							<td align="center" valign="middle">2072 ± 242</td>
							<td align="center" valign="middle">2098 ± 279</td>
							<td align="center" valign="middle">2087 ± 264</td>
							<td align="center" valign="middle">0,296<xref ref-type="table-fn" rid="TFN2">*</xref>
							</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle">TMDG, mmHg%</td>
							<td align="center" valign="middle">103 (38; 529)</td>
							<td align="center" valign="middle">79 (39;455)</td>
							<td align="center" valign="middle">75 (39; 375)</td>
							<td align="center" valign="middle">0,092<xref ref-type="table-fn" rid="TFN3">†</xref>
							</td>
						</tr>
						<tr>
							<td align="left" valign="middle">ETMG, %</td>
							<td align="center" valign="middle">94 (80; 98)</td>
							<td align="center" valign="middle">96 (82; 98)</td>
							<td align="center" valign="middle">96 (84;98)</td>
							<td align="center" valign="middle">0,208<xref ref-type="table-fn" rid="TFN3">†</xref>
							</td>
						</tr>
					</tbody>
				</table>
				<table-wrap-foot>
					<fn id="TFN2">
						<label>*</label>
						<p>ANOVA.</p>
					</fn>
					<fn id="TFN3">
						<label>†</label>
						<p>Friedman's analysis of variance;</p>
					</fn>
					<fn id="TFN4">
						<p>TDI: tissue Doppler imaging; GWI: Global Work Index; GCW: Global Constructive Work; GWW: Global Wasted Work; GWE: Global Work Efficiency; VA: visual analysis</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
			<table-wrap id="t3">
				<label>Tabela 3</label>
				<caption>
					<title>Comparação das diferenças das médias entre os índices de TM de acordo com as formas diferentes de aferição dos eventos valvares, análise post-hoc</title>
				</caption>
				<table frame="hsides" rules="none">
					<colgroup width="33%">
						<col/>
						<col/>
						<col/>
					</colgroup>
					<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
						<tr style="background-color:#C58874">
							<th align="left" valign="top"/>
							<th align="center" valign="top">Visual</th>
							<th align="center" valign="middle">TDI</th>
						</tr>
					</thead>
					<tbody style="border-bottom: thin solid; border-color: #000000">
						<tr>
							<td align="left" valign="middle"><bold>GWI</bold></td>
							<td align="center" valign="middle"/>
							<td align="center" valign="middle"/>
						</tr>
						<tr>
							<td align="left" valign="middle">TDI</td>
							<td align="center" valign="middle">162 (p&lt;0.001<xref ref-type="table-fn" rid="TFN5">*</xref>)</td>
							<td align="center" valign="middle">----------------------------</td>
						</tr>
						<tr>
							<td align="left" valign="middle">PD</td>
							<td align="center" valign="middle">350 (p&lt;0.001<xref ref-type="table-fn" rid="TFN5">*</xref>)</td>
							<td align="center" valign="middle">168 (p=0.216<xref ref-type="table-fn" rid="TFN5">*</xref>)</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle"><bold>GCW</bold></td>
							<td align="center" valign="middle"/>
							<td align="center" valign="middle"/>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle">TDI</td>
							<td align="center" valign="middle">26 (p=0.121<xref ref-type="table-fn" rid="TFN5">*</xref>)</td>
							<td align="center" valign="middle">----------------------------</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle">PD</td>
							<td align="center" valign="middle">15 (p=0.383<xref ref-type="table-fn" rid="TFN5">*</xref>)</td>
							<td align="center" valign="middle">-11 (p=0.492<xref ref-type="table-fn" rid="TFN5">*</xref>)</td>
						</tr>
						<tr>
							<td align="left" valign="middle"><bold>GWW</bold></td>
							<td align="center" valign="middle"/>
							<td align="center" valign="middle"/>
						</tr>
						<tr>
							<td align="left" valign="middle">TDI</td>
							<td align="center" valign="middle">-24 (p=0.202<xref ref-type="table-fn" rid="TFN6">†</xref>)</td>
							<td align="center" valign="middle">----------------------------</td>
						</tr>
						<tr>
							<td align="left" valign="middle">PD</td>
							<td align="center" valign="middle">-28 (p=0.051<xref ref-type="table-fn" rid="TFN6">†</xref>)</td>
							<td align="center" valign="middle">-4 (p=0.793<xref ref-type="table-fn" rid="TFN6">†</xref>)</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle"><bold>GWE</bold></td>
							<td align="center" valign="middle"/>
							<td align="center" valign="middle"/>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle">TDI</td>
							<td align="center" valign="middle">2 (p=0.359<xref ref-type="table-fn" rid="TFN6">†</xref>)</td>
							<td align="center" valign="middle">----------------------------</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle">PD</td>
							<td align="center" valign="middle">2 (p=0.123<xref ref-type="table-fn" rid="TFN6">†</xref>)</td>
							<td align="center" valign="middle">0 (p=0.862<xref ref-type="table-fn" rid="TFN6">†</xref>)</td>
						</tr>
					</tbody>
				</table>
				<table-wrap-foot>
					<fn id="TFN5">
						<label>*</label>
						<p>Pairwise comparison test of marginal linear predictions.</p>
					</fn>
					<fn id="TFN6">
						<label>†</label>
						<p>Bonferroni test.</p>
					</fn>
					<fn id="TFN7">
						<p>TDI: tissue Doppler imaging; GWI: Global Work Index; GCW: Global Constructive Work; GWW: Global Wasted Work; GWE: Global Work Efficiency; PD: pulsed Doppler</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
			<fig id="f1">
				<label>Figure 1</label>
				<caption>
					<title>General agreement for GWI; Bland-Altman plots showing the agreement of GWI with PD versus VA (A), TDI versus VA (B) and TDI versus PD</title>
				</caption>
				<graphic xlink:href="2675-312X-abcimg-37-04-e20240093-gf02.tif"/>
			</fig>
			<fig id="f2">
				<label>Figure 2</label>
				<caption>
					<title>General agreement for GCW; Bland-Altman plots showing the agreement of GCW with PD versus VA (A), TDI versus VA (B) and TDI versus PD.</title>
				</caption>
				<graphic xlink:href="2675-312X-abcimg-37-04-e20240093-gf03.tif"/>
			</fig>
			<fig id="f3">
				<label>Figure 3</label>
				<caption>
					<title>General agreement for GWW; Bland-Altman plots showing the agreement of GWW with PD versus VA (A), TDI versus VA (B) and TDI versus PD</title>
				</caption>
				<graphic xlink:href="2675-312X-abcimg-37-04-e20240093-gf04.tif"/>
			</fig>
			<fig id="f4">
				<label>Figure 4</label>
				<caption>
					<title>General agreement for GWE; Bland-Altman plots showing the agreement of GWE with PD versus VA (A), TDI versus VA (B) and TDI versus PD</title>
				</caption>
				<graphic xlink:href="2675-312X-abcimg-37-04-e20240093-gf05.tif"/>
			</fig>
			<p>
				<xref ref-type="table" rid="t4">Table 4</xref> describes relationships between the results, demonstrating a significant difference in the times of mitral valve closing and aortic opening between the three methods for VET estimation. According to both TDI and PD, mitral valve closing occurred at a later stage, whereas aortic valve opening at an earlier stage as compared with VA.</p>
			<table-wrap id="t4">
				<label>Table 4</label>
				<caption>
					<title>Comparison of VET according to the method applied to estimate VET</title>
				</caption>
				<table frame="hsides" rules="none">
					<colgroup width="20%">
						<col/>
						<col/>
						<col/>
						<col/>
						<col/>
					</colgroup>
					<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
						<tr style="background-color:#C58874">
							<th align="left" valign="top">VET (ms)</th>
							<th align="center" valign="middle">VA</th>
							<th align="center" valign="middle">TDI</th>
							<th align="center" valign="middle">PD</th>
							<th align="center" valign="middle">p</th>
						</tr>
					</thead>
					<tbody style="border-bottom: thin solid; border-color: #000000">
						<tr>
							<td align="left" valign="middle">Mitral valve opening</td>
							<td align="center" valign="middle">462 (363;529)</td>
							<td align="center" valign="middle">416 (326;537)</td>
							<td align="center" valign="middle">434 (358;492)</td>
							<td align="center" valign="middle">0.979<xref ref-type="table-fn" rid="TFN8">*</xref>
							</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle">Mitral valve closing</td>
							<td align="center" valign="middle">3 (0;33)</td>
							<td align="center" valign="middle">20 (1;45)</td>
							<td align="center" valign="middle">15 (0;43)</td>
							<td align="center" valign="middle">0.021<xref ref-type="table-fn" rid="TFN8">*</xref>
							</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Aortic valve opening</td>
							<td align="center" valign="middle">93 (36;128)</td>
							<td align="center" valign="middle">48 (11;98)</td>
							<td align="center" valign="middle">53 (13;358)</td>
							<td align="center" valign="middle">&lt;0.001<xref ref-type="table-fn" rid="TFN8">*</xref>
							</td>
						</tr>
						<tr style="background-color:#E7CCBF">
							<td align="left" valign="middle">Aortic valve closing</td>
							<td align="center" valign="middle">370 (274;449)</td>
							<td align="center" valign="middle">347 (277;402)</td>
							<td align="center" valign="middle">342 (65;389)</td>
							<td align="center" valign="middle">0.989<xref ref-type="table-fn" rid="TFN8">*</xref>
							</td>
						</tr>
					</tbody>
				</table>
				<table-wrap-foot>
					<fn id="TFN8">
						<label>*</label>
						<p>Friedman's analysis of variance.</p>
					</fn>
					<fn id="TFN9">
						<p>TDI: tissue Doppler imaging. VET: valvular event times; VA: visual analysis; PD: pulsed Doppler; TDI: tissue Doppler imaging</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
		</sec>
		<sec sec-type="discussion">
			<title>Discussion</title>
			<p>The present study evaluated the impact of different methods of VET estimation on MW indexes. The results indicated that GWI was influenced by the method, with lower values obtained by VA as compared with TDI and PD, which demonstrated similar results. The <xref ref-type="fig" rid="f9">Central Figure</xref> shows an example of GWI calculation using the three methods, reinforcing the significant difference observed with VA. However, no significant differences between the methods were found for estimation of other indexes such as GCW, GWW, or GWE, suggesting a lower sensitivity of these indexes to the method used.</p>
			<p>These differences may be explained by the higher susceptibility of VA to errors, due to observer's subjectivity and lower temporal resolution, in contrast to the objective accuracy of TDI and PD, resulting in differences in VET values and ultimately in MW estimates. Changes in valvular times, such as in aortic valve opening time, may have influenced the GWI values obtained by VA, by reducing the time of ejection as compared with other methods. Since all other factors related to pressure-strain loop were maintained constant and the GLS was the same in all groups, differences in GWI obtained by the three methods may be attributed to differences in VETs. In the study by Russell et a.,<sup><xref ref-type="bibr" rid="B7">7</xref></sup> changes in aortic valve opening and closing times did not affect the GWI values, differently from our findings and those reported by Olsen et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
			<p>The study by Olsen et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> was the only similar publication that included four subtypes of subjects – healthy subjects, subjects with atherosclerosis, subjects with atrial fibrillation during the echocardiographic examination, and subjects with reduced ejection fraction. The methods for VET estimation were VA, PD and TDI M-mode. Our results are in accordance with the results reported by these authors,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> showing that GWI, when estimated by VA, was lower when compared with Doppler-based methods. These findings were similar in all subgroups of subjects evaluated, including the sample of healthy individuals.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
			<p>An important study on normal ranges for MW demonstrated an intra-observer and inter-observer variability for GWI of 42.2mmHg% and 34.6mmHg%, respectively.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> In our study, GWI yielded by VA was significantly different from that estimated by both TDI and PD, with differences of 162mmHg% (9.2%) and 350mmHg% (20%), respectively. These differences were much higher than the intra-observer variation reported by Manganaro et al.,<sup><xref ref-type="bibr" rid="B9">9</xref></sup> which may be considered high enough to impact the clinical assessment of heart disease patients.<sup><xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup> These findings highlight the importance of standardizing a single method, ideally a Doppler-based methods, due to its higher temporal resolution.</p>
			<p>Among the main limitations of the study, the fact that it has been conducted in a single center and by one investigator may cause selection bias, since the studied population may not be representative of other regions or health systems. In addition, the study included only patients without comorbidities, which restricts the extrapolation of the results to individuals with more complex cardiac diseases, like heart failure, hypertension and ischemic diseases. All measurements were made by one observer, which limits the evaluation of inter-observer variability, which is an important parameter to validate the reproducibility of the results.</p>
			<p>Due to scarcity of data in the literature, further studies are needed to confirm or not our results, making it possible to standardize and to validate the best method to estimate VET, and strengthen the use of MW.</p>
		</sec>
		<sec sec-type="conclusions">
			<title>Conclusion</title>
			<p>This study demonstrated that GWI is sensitive to VET estimates, with significant differences between VA, TGI and PD. VA resulted in underestimation of GWI as compared to Doppler-based methods, which showed higher agreement for VET estimation. However, other myocardial indexes (GCW, GWW and GWE) were not influenced by the methodology applied. The standardization of the methods used for VET estimation, preferably Doppler-based methods, is recommended to improve the accuracy of MW calculation, especially in studies that involve healthy populations and heart disease patients. Future studies are needed to confirm these findings and establish the most appropriate method.</p>
		</sec>
	</body>
	<back>
		<fn-group>
			<fn fn-type="financial-disclosure" id="fn1">
				<label>Sources of Funding</label>
				<p>There were no external funding sources for this study.</p>
			</fn>
			<fn fn-type="other" id="fn2">
				<label>Study Association</label>
				<p>This study is not associated with any thesis or dissertation work.</p>
			</fn>
			<fn fn-type="other" id="fn3">
				<label>Ethics Approval and Consent to Participate</label>
				<p>This study was approved by the Ethics Committee of the São Domingos under the protocol number 6.777.966. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
			</fn>
		</fn-group>
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					<pub-id pub-id-type="doi">10.1016/j.echo.2021.04.013</pub-id>
				</element-citation>
				<mixed-citation>8 Roemer S, Jaglan A, Santos D, Umland M, Jain R, Tajik AJ, et al. The Utility of Myocardial Work in Clinical Practice. J Am Soc Echocardiogr. 2021;34(8):807-18. doi: 10.1016/j.echo.2021.04.013.</mixed-citation>
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						</name>
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							<surname>Dulgheru</surname>
							<given-names>R</given-names>
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						<name>
							<surname>Ilardi</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Sugimoto</surname>
							<given-names>T</given-names>
						</name>
						<name>
							<surname>Robinet</surname>
							<given-names>S</given-names>
						</name>
						<etal/>
					</person-group>
					<article-title>Echocardiographic Reference Ranges for Normal Non-Invasive Myocardial Work Indices: Results from the EACVI NORRE Study</article-title>
					<source>Eur Heart J Cardiovasc Imaging</source>
					<year>2019</year>
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				<mixed-citation>9 Manganaro R, Marchetta S, Dulgheru R, Ilardi F, Sugimoto T, Robinet S, et al. Echocardiographic Reference Ranges for Normal Non-Invasive Myocardial Work Indices: Results from the EACVI NORRE Study. Eur Heart J Cardiovasc Imaging. 2019;20(5):582-90. doi: 10.1093/ehjci/jey188.</mixed-citation>
			</ref>
		</ref-list>
	</back>
	<sub-article article-type="translation" id="S1" xml:lang="pt">
		<front-stub>
			<article-id pub-id-type="doi">10.36660/abcimg.20240093</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Artigo Original</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Impacto dos Métodos de Avaliação dos Tempos de Eventos Valvares no Cálculo do Trabalho Miocárdico pela Ecocardiografia</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-7900-6506</contrib-id>
					<name>
						<surname>Pereira</surname>
						<given-names>Marcio Mendes</given-names>
					</name>
					<role>Concepção e desenho da pesquisa</role>
					<role>redação do manuscrito</role>
					<role>obtenção de dados e análise estatística</role>
					<role>análise e interpretação dos dados</role>
					<role>revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
					<xref ref-type="corresp" rid="c2"/>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0003-3799-8057</contrib-id>
					<name>
						<surname>Monteiro</surname>
						<given-names>Francisco das Chagas</given-names>
						<suffix>Júnior</suffix>
					</name>
					<role>Concepção e desenho da pesquisa</role>
					<role>redação do manuscrito</role>
					<role>revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0004-4443-0552</contrib-id>
					<name>
						<surname>Yamamura</surname>
						<given-names>Sayuri</given-names>
					</name>
					<role>Concepção e desenho da pesquisa</role>
					<role>redação do manuscrito</role>
					<role>análise e interpretação dos dados</role>
					<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
				</contrib>
				<aff id="aff3">
					<label>1</label>
					<addr-line>
						<named-content content-type="city">São Luis</named-content>
						<named-content content-type="state">MA</named-content>
					</addr-line>
					<country country="BR">Brasil</country>
					<institution content-type="original">UDI Hospital, São Luis, MA – Brasil</institution>
				</aff>
				<aff id="aff4">
					<label>2</label>
					<addr-line>
						<named-content content-type="city">São Luis</named-content>
						<named-content content-type="state">MA</named-content>
					</addr-line>
					<country country="BR">Brasil</country>
					<institution content-type="original">Universidade Federal do Maranhão, São Luis, MA – Brasil</institution>
				</aff>
			</contrib-group>
			<author-notes>
				<corresp id="c2">
					<label>Correspondência:</label><bold>Marcio Mendes Pereira</bold> • UDI Hospital. Av. Prof. Carlos Cunha, 2000. CEP: <postal-code>65076-820</postal-code>. Jaracati, São Luis, MA – Brasil E-mail: <email>marciomp50@hotmail.com</email>
				</corresp>
				<fn fn-type="conflict">
					<label>Potencial Conflito de Interesse</label>
					<p>Declaro não haver conflito de interesses pertinentes</p>
				</fn>
				<fn fn-type="edited-by">
					<label>Editor responsável pela revisão:</label>
					<p>Marcelo Tavares</p>
				</fn>
			</author-notes>
			<abstract>
				<title>Resumo</title>
				<sec>
					<title>Fundamento:</title>
					<p>A fração de ejeção do ventrículo esquerdo (FEVE) é o parâmetro tradicional na avaliação da função cardíaca, porém apresenta limitações na detecção precoce de disfunção. O <italic>Strain</italic> Longitudinal Global (SLG) e o Trabalho Miocárdico (TM) são alternativas promissoras, sendo este último menos influenciado pelas condições de carga. O cálculo do TM depende dos tempos dos eventos valvares (TEV), obtidos por métodos que podem gerar resultados divergentes.</p>
				</sec>
				<sec>
					<title>Objetivos:</title>
					<p>Comparar o impacto das diferentes formas de aferição dos TEV, sendo elas: análise visual (AV), Doppler tecidual (TDI) e Doppler pulsátil (DP) nos Índice de Trabalho Miocárdico Global (ITMG), Trabalho Miocárdico Construtivo Global (TMCG), Trabalho Miocárdico Desperdiçado Global (TMDG) e Eficiência do Trabalho Miocárdico Global (ETMG).</p>
				</sec>
				<sec>
					<title>Método:</title>
					<p>Estudo clínico transversal com 35 pacientes saudáveis, que foram submetidos a ecocardiografia entre outubro de 2022 e março de 2023. O TM foi avaliado por meio do software EchoPAC, com aferição dos TEV por AV, TDI e DP. Os resultados foram analisados por testes de ANOVA e Friedman, seguidos de análises post-hoc com nível de significância de 5%.</p>
				</sec>
				<sec>
					<title>Resultados:</title>
					<p>O ITMG apresentou variação significativa entre os métodos de aferição dos TEV, sendo menor pela AV em comparação ao TDI e DP (p&lt;0,001). Os índices TMCG, TMDG e ETMG não demonstraram diferença estatisticamente significativa entre os métodos.</p>
				</sec>
				<sec>
					<title>Conclusões:</title>
					<p>O método de aferição dos TEV implica em diferença estatisticamente significativa no ITMG, mas não afeta os demais índices de TM.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="pt">
				<title>Palavras-chave:</title>
				<kwd>Ecocardiografia</kwd>
				<kwd>Disfunção Ventricular Esquerda</kwd>
				<kwd>Função Ventricular</kwd>
			</kwd-group>
		</front-stub>
		<body>
			<sec sec-type="intro">
				<title>Introdução</title>
				<p>A Fração de Ejeção do Ventrículo Esquerdo (FEVE) tem sido amplamente utilizada na avaliação da função sistólica em diversas condições clínicas, especialmente nas doenças cardíacas. No entanto, estudos demonstram que a FEVE apresenta limitações, especialmente na detecção precoce de disfunção cardíaca em pacientes com fração de ejeção preservada, mas com comprometimento funcional subclínico. Diante disso, novas técnicas ecocardiográficas, como o <italic>Strain</italic> Longitudinal Global (SLG), vêm ganhando espaço, proporcionando uma avaliação mais sensível da deformação miocárdica.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup></p>
				<fig id="f10">
					<caption>
						<title>Determinação do TM. Obtenção dos tempos eventos valvares pela AV, DP do fluxo mitral e da via de saída do VE e TDI do anel mitral. Usando a imagem de função automatizada, o SLG do VE é gerado pelas janelas apical 2, 3 e 4 câmaras. O ITMG usando os marcadores de eventos pela AV é menor que os obtidos pelo TDI e pulsátil. PVE: Pressão Ventricular Esquerda; ITMG: Índice de Trabalho Miocárdico Global.</title>
					</caption>
					<graphic xlink:href="2675-312X-abcimg-37-04-e20240093-gf01-pt.tif"/>
				</fig>
				<p>Mais recentemente, a introdução do conceito de Trabalho Miocárdico (TM) trouxe um avanço na capacidade de avaliar a função cardíaca de maneira mais completa, considerando a interação entre a deformação e a pós-carga que o miocárdio enfrenta durante o ciclo cardíaco. Ao contrário do SLG, o TM é menos influenciado pelas condições de pré e pós-carga, o que pode fornecer uma estimativa mais robusta da função miocárdica.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup></p>
				<p>Para calcular o TM, é essencial a identificação precisa dos tempos dos eventos valvares (TEV), especialmente os relacionados à abertura e fechamento da valva aórtica. Esses tempos podem ser obtidos por diferentes métodos, incluindo análise visual (AV), Doppler Tecidual (TDI, do inglês <italic>tissue doppler imaging</italic>) e Doppler pulsado (DP). No entanto, não há consenso sobre qual método é mais acurado e quais as implicações nos índices de TM, sendo eles Índice de Trabalho Miocárdico Global (ITMG), Trabalho Miocárdico Construtivo Global (TMCG), Trabalho Miocárdico Desperdiçado Global (TMDG) e Eficiência do Trabalho Miocárdico Global (ETMG) permanecem pouco exploradas.<sup><xref ref-type="bibr" rid="B5">5</xref>-<xref ref-type="bibr" rid="B8">8</xref></sup></p>
				<p>O objetivo do presente estudo foi comparar avaliar se há diferença significativa entre as distintas formas de medição dos TEV na determinação do TM.</p>
			</sec>
			<sec sec-type="methods">
				<title>Metodologia</title>
				<p>Foi realizado um estudo clínico transversal com 35 pacientes em um hospital privado de São Luís, no Estado do Maranhão, entre outubro de 2022 e março de 2023. Os pacientes, maiores de 18 anos e sem comorbidades, foram submetidos a exames de ecocardiografia. As avaliações ecocardiográficas seguiram as recomendações da <italic>American Society of Echocardiography</italic> (ASE), com imagens bidimensionais gravadas em três ciclos, sincronizadas pelo complexo QRS, para análise offline no software EchoPAC (versão 202, GE Vingmed Ultrasound). A FEVE foi determinada pelo método de Simpson.</p>
				<p>O ITMG foi quantificado calculando a taxa de encurtamento regional por diferenciação do traçado do <italic>strain</italic> longitudinal e multiplicando pela pressão instantânea do Ventrículo Esquerdo (VE). Essa medida instantânea foi integrada ao longo do tempo, para medir o TM em função do tempo durante a sístole (intervalo de tempo desde o fechamento da valva mitral até a abertura da valva mitral). Durante a ejeção do VE, os segmentos foram analisados para TMD e/ou TMC, com valores globais determinados como as médias de todos os valores segmentares e exibidos no diagrama de circuito pressão-deformação do VE.</p>
				<p>Os principais parâmetros calculados foram: ITMG (mmHg%), área da curva de pressão do VE; TMCG (mmHg%), estimativa do trabalho dos segmentos do VE; TMDG (mmHg%), estimativa do trabalho negativo dos segmentos do VE; e ETMG (mmHg%), definida pela razão entre TMCG e a soma de TMCG e TMDG.</p>
				<p>As variáveis categóricas foram expressas como frequências absolutas e relativas, e as contínuas como médias e desvio-padrão, ou medianas, dependendo da distribuição. O teste de Shapiro-Wilk foi aplicado para verificar a normalidade dos dados (p&lt;0,05).</p>
				<p>O tamanho amostral foi calculado para detectar uma diferença de 123mmHg% no ITMG entre os métodos, com poder de 90% e nível de significância de 5%. As comparações de médias foram realizadas com ANOVA para dados paramétricos e o teste de Friedman para dados não paramétricos. Testes post-hoc, como comparações de pares de predições lineares marginais e o teste de Bonferroni, foram aplicados para identificar diferenças significativas. A análise estatística foi realizada no Stata® Intercooled versão 18.0.</p>
				<p>O estudo foi aprovado pelo Comitê de Ética do Hospital e Maternidade São Domingos (CAAE 71514222.1.0000.5085).</p>
			</sec>
			<sec sec-type="results">
				<title>Resultados</title>
				<p>A média de idade foi de 38,9 anos (variação de 18 a 60 anos), com predominância masculina (57,1%). Os parâmetros clínicos e ecocardiográficos estão resumidos na <xref ref-type="table" rid="t5">Tabela 1</xref>. As médias das medidas ecocardiográficas estavam dentro dos limites de normalidade, refletindo o perfil saudável dos participantes de escolha da amostragem.</p>
				<table-wrap id="t5">
					<label>Tabela 1</label>
					<caption>
						<title>Características gerais e ecocardiográficas dos pacientes avaliados</title>
					</caption>
					<table frame="hsides" rules="none">
						<colgroup width="49%">
							<col width="1%"/>
							<col/>
							<col/>
						</colgroup>
						<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
							<tr style="background-color:#C58874">
								<th align="left" colspan="2" valign="top">Variáveis</th>
								<th align="center" valign="middle">TOTAL (n = 35)</th>
							</tr>
						</thead>
						<tbody style="border-bottom: thin solid; border-color: #000000">
							<tr style="background-color:#E7CCBF">
								<td align="left" colspan="2" valign="middle"><bold>Perfil clínico</bold></td>
								<td align="center" valign="middle"/>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" colspan="2" valign="middle">Idade</td>
								<td align="center" valign="middle">38,88 (18; 60)</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" colspan="2" valign="middle">Sexo (%)</td>
								<td align="center" valign="middle"/>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle"/>
								<td align="left" valign="middle">Homens</td>
								<td align="center" valign="middle">57,14</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle"/>
								<td align="left" valign="middle">Mulheres</td>
								<td align="center" valign="middle">42,86</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" colspan="2" valign="middle">Superfície corpórea (cm²)</td>
								<td align="center" valign="middle">1,87 ± 0,21</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" colspan="2" valign="middle">Altura (m)</td>
								<td align="center" valign="middle">1,68 (1,50; 1,88)</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" colspan="2" valign="middle">Peso (Kg)</td>
								<td align="center" valign="middle">77 (51; 124)</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" colspan="2" valign="middle">Pressão arterial sistólica (mmHg)</td>
								<td align="center" valign="middle">114 ± 9</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" colspan="2" valign="middle">Pressão arterial diastólica (mmHg)</td>
								<td align="center" valign="middle">72 ± 7</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" colspan="2" valign="middle">Frequência cardíaca (bpm)</td>
								<td align="center" valign="middle">67 (47; 94)</td>
							</tr>
							<tr>
								<td align="left" colspan="2" valign="middle"><bold>Dados ecocardiográficos</bold></td>
								<td align="center" valign="middle"/>
							</tr>
							<tr>
								<td align="left" colspan="2" valign="middle">Diâmetro diastólico final (mm)</td>
								<td align="center" valign="middle">4,84 ± 0,44</td>
							</tr>
							<tr>
								<td align="left" colspan="2" valign="middle">Diâmetro sistólico final (mm)</td>
								<td align="center" valign="middle">2,98 ± 0,35</td>
							</tr>
							<tr>
								<td align="left" colspan="2" valign="middle">Espessura do septo (mm):</td>
								<td align="center" valign="middle">0,82 ± 0,08</td>
							</tr>
							<tr>
								<td align="left" colspan="2" valign="middle">Volume Diastólico Final (mmHg):</td>
								<td align="center" valign="middle">90 ± 25</td>
							</tr>
							<tr>
								<td align="left" colspan="2" valign="middle">Volume Sistólico Final (mmHg)</td>
								<td align="center" valign="middle">32 ± 12</td>
							</tr>
							<tr>
								<td align="left" colspan="2" valign="middle">Volume do AE (mmHg)</td>
								<td align="center" valign="middle">24 ± 4</td>
							</tr>
							<tr>
								<td align="left" colspan="2" valign="middle">Fração de Ejeção (mmHg)</td>
								<td align="center" valign="middle">65 ± 3</td>
							</tr>
							<tr>
								<td align="left" colspan="2" valign="middle">Índice de Massa de VE, (g/m²)</td>
								<td align="center" valign="middle">71 (48; 95,9)</td>
							</tr>
							<tr>
								<td align="left" colspan="2" valign="middle">Taxa de quadros, (quadros/s)</td>
								<td align="center" valign="middle">73 ± 52</td>
							</tr>
							<tr>
								<td align="left" colspan="2" valign="middle">SLG (%)</td>
								<td align="center" valign="middle">19 ± 1,8</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN10">
							<p>SLG: Strain Longitudinal Global; AE: átrio esquerdo; VE: ventrículo esquerdo.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
				<p>A <xref ref-type="table" rid="t6">Tabela 2</xref> apresenta a comparação entre os índices de TM conforme o método utilizado para estimativa dos TEV. Observou-se que os valores obtidos pelo método de AV foram significativamente diferentes (p&lt;0,001) que os obtidos pelos dois métodos derivados do Doppler (TDI e DP). Especificamente, a média dos valores de ITMG foi menor com a AV, quando comparada ao TDI e DP. Entretanto, os outros índices miocárdicos não apresentaram variação significativa entre si, conforme demonstrado nas <xref ref-type="table" rid="t6">Tabelas 2</xref> e <xref ref-type="table" rid="t7">3</xref>. Esses resultados foram distribuídos no gráfico de Bland-Altman para demonstração visual do grau de concordância entre os valores pelos diferentes métodos de TEV. Na <xref ref-type="fig" rid="f5">Figura 1</xref>, é possível observar uma maior dispersão de pontos nos quadros A e B, o que significa que há menor grau de concordância entre os valores coletados. As <xref ref-type="fig" rid="f6">Figuras 2</xref>, <xref ref-type="fig" rid="f7">3</xref> e <xref ref-type="fig" rid="f8">4</xref> corroboram a ausência de diferença estatística nos índices de TM obtidos por diferentes métodos.</p>
				<table-wrap id="t6">
					<label>Tabela 2</label>
					<caption>
						<title>Comparação dos índices de TM de acordo com as formas diferentes de aferição dos TEV</title>
					</caption>
					<table frame="hsides" rules="none">
						<colgroup width="20%">
							<col/>
							<col/>
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
							<tr style="background-color:#C58874">
								<th align="left" valign="top">Índices miocárdicos</th>
								<th align="center" valign="middle">Avaliação visual</th>
								<th align="center" valign="middle">TDI</th>
								<th align="center" valign="middle">DP</th>
								<th align="center" valign="middle">p</th>
							</tr>
						</thead>
						<tbody style="border-bottom: thin solid; border-color: #000000">
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle">ITMG, mmHg%</td>
								<td align="center" valign="middle">1748 ± 258</td>
								<td align="center" valign="middle">1910 ± 264</td>
								<td align="center" valign="middle">2098 ± 279</td>
								<td align="center" valign="middle">&lt;0,001<xref ref-type="table-fn" rid="TFN11">*</xref>
								</td>
							</tr>
							<tr>
								<td align="left" valign="middle">TMCG, mmHg%</td>
								<td align="center" valign="middle">2072 ± 242</td>
								<td align="center" valign="middle">2098 ± 279</td>
								<td align="center" valign="middle">2087 ± 264</td>
								<td align="center" valign="middle">0,296<xref ref-type="table-fn" rid="TFN11">*</xref>
								</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle">TMDG, mmHg%</td>
								<td align="center" valign="middle">103 (38; 529)</td>
								<td align="center" valign="middle">79 (39;455)</td>
								<td align="center" valign="middle">75 (39; 375)</td>
								<td align="center" valign="middle">0,092<xref ref-type="table-fn" rid="TFN12">†</xref>
								</td>
							</tr>
							<tr>
								<td align="left" valign="middle">ETMG, %</td>
								<td align="center" valign="middle">94 (80; 98)</td>
								<td align="center" valign="middle">96 (82; 98)</td>
								<td align="center" valign="middle">96 (84;98)</td>
								<td align="center" valign="middle">0,208<xref ref-type="table-fn" rid="TFN12">†</xref>
								</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN11">
							<label>*</label>
							<p>Teste de ANOVA.</p>
						</fn>
						<fn id="TFN12">
							<label>†</label>
							<p>Teste de análise de variância de Friedman</p>
						</fn>
						<fn id="TFN13">
							<p>ITMG: Índice de Trabalho Miocárdico Global; TMCG: Trabalho Miocárdico Construtivo Global; TMDG: Trabalho Miocárdico Desperdiçado Global; ETMG: Eficiência do Trabalho Miocárdico Global; TDI: Doppler tecidual; DP: Doppler pulsado; ITMG: Índice de Trabalho Miocárdico Global; TMCG: Trabalho Miocárdico Construtivo Global; TMDG: Trabalho Miocárdico Desperdiçado Global; ETMG: Eficiência do Trabalho Miocárdico Global.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
				<table-wrap id="t7">
					<label>Tabela 3</label>
					<caption>
						<title>Comparação das diferenças das médias entre os índices de TM de acordo com as formas diferentes de aferição dos eventos valvares, análise post-hoc</title>
					</caption>
					<table frame="hsides" rules="none">
						<colgroup width="33%">
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
							<tr style="background-color:#C58874">
								<th align="left" valign="top"/>
								<th align="center" valign="top">Visual</th>
								<th align="center" valign="middle">TDI</th>
							</tr>
						</thead>
						<tbody style="border-bottom: thin solid; border-color: #000000">
							<tr>
								<td align="left" valign="middle"><bold>GWI</bold></td>
								<td align="center" valign="middle"/>
								<td align="center" valign="middle"/>
							</tr>
							<tr>
								<td align="left" valign="middle">TDI</td>
								<td align="center" valign="middle">162 (p&lt;0.001<xref ref-type="table-fn" rid="TFN14">*</xref>)</td>
								<td align="center" valign="middle">----------------------------</td>
							</tr>
							<tr>
								<td align="left" valign="middle">PD</td>
								<td align="center" valign="middle">350 (p&lt;0.001<xref ref-type="table-fn" rid="TFN14">*</xref>)</td>
								<td align="center" valign="middle">168 (p=0.216<xref ref-type="table-fn" rid="TFN14">*</xref>)</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle"><bold>GCW</bold></td>
								<td align="center" valign="middle"/>
								<td align="center" valign="middle"/>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle">TDI</td>
								<td align="center" valign="middle">26 (p=0.121<xref ref-type="table-fn" rid="TFN14">*</xref>)</td>
								<td align="center" valign="middle">----------------------------</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle">PD</td>
								<td align="center" valign="middle">15 (p=0.383<xref ref-type="table-fn" rid="TFN14">*</xref>)</td>
								<td align="center" valign="middle">-11 (p=0.492<xref ref-type="table-fn" rid="TFN14">*</xref>)</td>
							</tr>
							<tr>
								<td align="left" valign="middle"><bold>GWW</bold></td>
								<td align="center" valign="middle"/>
								<td align="center" valign="middle"/>
							</tr>
							<tr>
								<td align="left" valign="middle">TDI</td>
								<td align="center" valign="middle">-24 (p=0.202<xref ref-type="table-fn" rid="TFN15">†</xref>)</td>
								<td align="center" valign="middle">----------------------------</td>
							</tr>
							<tr>
								<td align="left" valign="middle">PD</td>
								<td align="center" valign="middle">-28 (p=0.051<xref ref-type="table-fn" rid="TFN15">†</xref>)</td>
								<td align="center" valign="middle">-4 (p=0.793<xref ref-type="table-fn" rid="TFN15">†</xref>)</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle"><bold>GWE</bold></td>
								<td align="center" valign="middle"/>
								<td align="center" valign="middle"/>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle">TDI</td>
								<td align="center" valign="middle">2 (p=0.359<xref ref-type="table-fn" rid="TFN15">†</xref>)</td>
								<td align="center" valign="middle">----------------------------</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle">PD</td>
								<td align="center" valign="middle">2 (p=0.123<xref ref-type="table-fn" rid="TFN15">†</xref>)</td>
								<td align="center" valign="middle">0 (p=0.862<xref ref-type="table-fn" rid="TFN15">†</xref>)</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN14">
							<label>*</label>
							<p>Pairwise comparison test of marginal linear predictions.</p>
						</fn>
						<fn id="TFN15">
							<label>†</label>
							<p>Bonferroni test.</p>
						</fn>
						<fn id="TFN16">
							<p>TDI: tissue Doppler imaging; GWI: Global Work Index; GCW: Global Constructive Work; GWW: Global Wasted Work; GWE: Global Work Efficiency; PD: pulsed Doppler</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
				<fig id="f5">
					<label>Figura 1</label>
					<caption>
						<title>Concordância geral para o ITMG. Gráficos de Bland-Altman mostrando a concordância do ITMG para as modalidades de DP versus avaliação visual (A), TDI versus avaliação visual (B) e TDI versus DP (C)</title>
					</caption>
					<graphic xlink:href="2675-312X-abcimg-37-04-e20240093-gf02-pt.tif"/>
				</fig>
				<fig id="f6">
					<label>Figura 2</label>
					<caption>
						<title>Concordância geral para o índice de TMCG. Gráficos de Bland– Altman mostrando a concordância do TMCG para DP versus avaliação visual (A), TDI versus avaliação visual (B) e TDI versus DP (C)</title>
					</caption>
					<graphic xlink:href="2675-312X-abcimg-37-04-e20240093-gf03-pt.tif"/>
				</fig>
				<fig id="f7">
					<label>Figura 3</label>
					<caption>
						<title>Concordância geral para o trabalho miocárdico global desperdiçado. Gráficos de Bland–Altman mostrando a concordância do TMDG para DP versus avaliação visual (A), TDI versus avaliação visual (B) e TDI versus DP (C)</title>
					</caption>
					<graphic xlink:href="2675-312X-abcimg-37-04-e20240093-gf04-pt.tif"/>
				</fig>
				<fig id="f8">
					<label>Figura 4</label>
					<caption>
						<title>Concordância geral para a eficiência do TM. Gráficos de Bland– Altman mostrando a concordância da eficiência do TM para DP versus avaliação visual (A), TDI versus avaliação visual (B) e TDI versus DP (C)</title>
					</caption>
					<graphic xlink:href="2675-312X-abcimg-37-04-e20240093-gf05-pt.tif"/>
				</fig>
				<p>Na <xref ref-type="table" rid="t8">Tabela 4</xref>, foram relacionados os resultados encontrados no estudo, evidenciando uma diferença estatística significativa nos tempos de fechamento mitral e abertura aórtica entre os três métodos de aferição do TEV. O TDI e o DP detectaram o fechamento mitral de forma mais tardia e a abertura aórtica de forma mais precoce, em comparação à AV.</p>
				<table-wrap id="t8">
					<label>Tabela 4</label>
					<caption>
						<title>Comparação dos TEV de acordo com as formas diferentes de aferição dos TEV.</title>
					</caption>
					<table frame="hsides" rules="none">
						<colgroup width="20%">
							<col/>
							<col/>
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
							<tr style="background-color:#C58874">
								<th align="left" valign="top">Tempo dos eventos valvares (ms)</th>
								<th align="center" valign="middle">Visual</th>
								<th align="center" valign="middle">TDI</th>
								<th align="center" valign="middle">Doppler</th>
								<th align="center" valign="middle">p</th>
							</tr>
						</thead>
						<tbody style="border-bottom: thin solid; border-color: #000000">
							<tr>
								<td align="left" valign="middle">Abertura mitral</td>
								<td align="center" valign="middle">462 (363;529)</td>
								<td align="center" valign="middle">416 (326;537)</td>
								<td align="center" valign="middle">434 (358;492)</td>
								<td align="center" valign="middle">0,979<xref ref-type="table-fn" rid="TFN17">*</xref>
								</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle">Fechamento mitral</td>
								<td align="center" valign="middle">3 (0;33)</td>
								<td align="center" valign="middle">20 (1;45)</td>
								<td align="center" valign="middle">15 (0;43)</td>
								<td align="center" valign="middle">0,021<xref ref-type="table-fn" rid="TFN17">*</xref>
								</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Abertura aórtica</td>
								<td align="center" valign="middle">93 (36;128)</td>
								<td align="center" valign="middle">48 (11;98)</td>
								<td align="center" valign="middle">53 (13;358)</td>
								<td align="center" valign="middle">&lt;0,001<xref ref-type="table-fn" rid="TFN17">*</xref>
								</td>
							</tr>
							<tr style="background-color:#E7CCBF">
								<td align="left" valign="middle">Fechamento aórtico</td>
								<td align="center" valign="middle">370 (274;449)</td>
								<td align="center" valign="middle">347 (277;402)</td>
								<td align="center" valign="middle">342 (65;389)</td>
								<td align="center" valign="middle">0,989<xref ref-type="table-fn" rid="TFN17">*</xref>
								</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN17">
							<label>*</label>
							<p>Teste de análise de variância de Friedman. TDI: Doppler tecidual.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
			</sec>
			<sec sec-type="discussion">
				<title>Discussão</title>
				<p>Este estudo avaliou o impacto dos diferentes métodos de obtenção dos TEV nos índices de TM. Os resultados indicaram que o ITMG foi influenciado pela forma de aferição dos TEV, com valores menores obtidos pelo método da AV em comparação ao TDI e ao DP, que mostraram concordância entre si. Na <xref ref-type="fig" rid="f10">Figura Central</xref>, é demonstrado um exemplo em que o ITMG foi calculado utilizando os três métodos, reforçando a variação significativa observada quando a AV foi utilizada. No entanto, para os demais índices, como o TMCG, TMDG e a ETMG, não foram identificadas diferenças significativas entre os métodos de obtenção dos TEV, sugerindo menor sensibilidade desses índices à variabilidade metodológica aplicada.</p>
				<p>As diferenças observadas podem ser explicadas pela maior suscetibilidade da AV a erros, devido à subjetividade do avaliador e menor resolução temporal, em contraste com a precisão objetiva do TDI e DP, resultando em diferenças nas medidas dos TEV e, consequentemente, na estimativa do TM. Alterações nos tempos valvares, como o tempo de abertura da valva aórtica, podem ter influenciado o ITMG com a AV, reduzindo o tempo de ejeção em comparação aos outros métodos. Uma vez que todos os outros fatores relacionados com a curva de pressão-strain foram mantidos constantes e que o SLG foi o mesmo em todos os grupos, as diferenças nos valores de ITMG obtidos pelos três métodos podem ser atribuídas aos diferentes TEV. Russell et al.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> observaram que mudanças nos tempos de abertura e fechamento da válvula aórtica não alteraram os resultados do ITMG, diferentemente do que foi observado no nosso estudo e no estudo de Olsen et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
				<p>O estudo de Olsen et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> foi a única publicação semelhante que incluiu na avaliação quatro subtipos de pacientes, sendo eles: saudáveis, com aterosclerose, com fibrilação atrial no momento da ecocardiografia e com FE reduzida. As diferentes metodologias abordadas no estudo foram a AV, DP e TDI modo M. Os resultados obtidos em nosso estudo foram consistentes com os descritos pelos autores, verificando que o ITMG obtido pela AV foi, em média, mais baixo que o estimado pelos outros métodos, que são baseados em Doppler. Esses resultados foram semelhantes em todos os subgrupos de indivíduos analisados, inclusive na amostra de indivíduos saudáveis.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
				<p>Um importante estudo sobre valores de normalidade de índices de TM demonstrou uma variação intra e inter-observador para o ITMG de respectivamente 42,2mmHg% e 34,6mmHg%.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> No nosso estudo, ao utilizar a AV para o cálculo do ITMG, houve uma diferença estatisticamente significativa de 162mmHg% (9,2%) em relação ao TDI, e de 350mmHg% (20%) em relação DP. Essas diferenças foram bem maiores do que a variação intra-observador relatada por Manganaro et al.,<sup><xref ref-type="bibr" rid="B9">9</xref></sup> que pode ser considerada grande o suficiente para impactar na interpretação clínica de pacientes com uma cardiopatia.<sup><xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup> Por isso, ressalta-se a importância de padronizar um único método, de preferência os derivados do Doppler, devido a sua melhor resolução temporal.</p>
				<p>As principais limitações deste estudo foram: o fato de haver sido realizado em um único centro e por um único observador pode introduzir viés de seleção, pois a população estudada pode não ser representativa de outras regiões ou sistemas de saúde; o estudo foi realizado exclusivamente com pacientes sem comorbidades, o que restringe a aplicabilidade dos resultados para indivíduos com condições cardiológicas mais complexas, como insuficiência cardíaca, hipertensão ou doenças isquêmicas; todas as medições foram realizadas por um único observador, o que limita a avaliação da variabilidade inter-observador, um parâmetro importante para validar a reprodutibilidade dos resultados.</p>
				<p>Devido à escassez de dados na literatura, estudos futuros serão necessários para confirmar ou não os resultados, possibilitando a padronização e a validação do melhor modo de realizar a medida dos TEV, potencializando o uso do TM.</p>
			</sec>
			<sec sec-type="conclusions">
				<title>Conclusão</title>
				<p>Este estudo demonstrou que o ITMG é sensível à forma de aferição dos TEV, com diferenças significativas entre os AV, TDI e DP. A AV resultou em uma subestimação do ITMG em relação aos métodos baseados em Doppler, que apresentaram maior concordância. No entanto, os outros índices miocárdicos (TMCG, TMDG e ETMG) não foram afetados pelos diferentes métodos de aferição. A padronização dos métodos de obtenção dos TEV, preferencialmente aqueles baseados em Doppler, é recomendada para melhorar a precisão do cálculo do TM, principalmente em estudos que envolvem populações saudáveis e cardiopatas. Estudos futuros serão necessários para confirmar esses achados e estabelecer uma a metodologia mais adequada.</p>
			</sec>
		</body>
		<back>
			<fn-group>
				<fn fn-type="financial-disclosure" id="fn4">
					<label>Fontes de Financiamento</label>
					<p>O presente estudo não teve fontes de financiamento externas.</p>
				</fn>
				<fn fn-type="other" id="fn5">
					<label>Vinculação Acadêmica</label>
					<p>Não há vinculação deste estudo a programas de pósgraduação.</p>
				</fn>
				<fn fn-type="other" id="fn6">
					<label>Aprovação Ética e Consentimento Informado</label>
					<p>Este estudo foi aprovado pelo Comitê de Ética do Hospital São Domingos sob o número de protocolo 6.777.966. Todos os procedimentos envolvidos nesse estudo estão de acordo com a Declaração de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes incluídos no estudo.</p>
				</fn>
			</fn-group>
		</back>
	</sub-article>
</article>