<?xml version="1.0" encoding="UTF-8"?>
<!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">dic</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="publisher-id">2675-312X/20223501eabc242</article-id>
			<article-id pub-id-type="doi">10.47593/2675-312X/20223501eabc242</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Artigo Original</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Right Ventricular Outflow Tract Acceleration Time: Correlation with Left Ventricular Diastolic Function, Sex, And Age</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<name>
						<surname>Coimbra</surname>
						<given-names>Renan Macedo</given-names>
					</name>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="corresp" rid="c1"/>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Camarozano</surname>
						<given-names>Ana Cristina</given-names>
					</name>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Sá</surname>
						<given-names>Cintia Rocha Fortes de</given-names>
					</name>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Carmo</surname>
						<given-names>Daniela de Castro</given-names>
					</name>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Fortunato</surname>
						<given-names>Jerônimo Antonio</given-names>
					</name>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Darwich</surname>
						<given-names>Rubens Zenóbio</given-names>
					</name>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Baroncini</surname>
						<given-names>Liz Andréa Villela</given-names>
					</name>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<aff id="aff1">
					<label>1</label>
					<institution content-type="orgname">Brazilian Red Cross</institution>
					<institution content-type="orgdiv1">Red Cross Hospital</institution>
					<addr-line>
						<named-content content-type="city">Curitiba</named-content>
						<named-content content-type="state">Paraná</named-content>
					</addr-line>
					<country country="BR">Brazil</country>
					<institution content-type="original">Red Cross Hospital – Brazilian Red Cross, Curitiba, Paraná, Brazil.</institution>
				</aff>
			</contrib-group>
			<author-notes>
				<corresp id="c1"><bold>Mailing Address: Renan Macedo Coimbra •</bold> E-mail: <email>renancoimbra@hotmail.com</email>
				</corresp>
				<fn fn-type="con">
					<p><bold>Authors’ contributions</bold></p>
					<p>Data collection: Coimbra RM, Baroncini LAV, Camarozano AC, Carmo DC, Sá CRF, Fortunato JA, Darwich RZ; Data analysis: Coimbra RM, Baroncini LAV, Camarozano AC, Carmo DC; Data design: Coimbra RM, Baroncini LAV, Camarozano AC; Manuscript writing: Coimbra RM, Baroncini LAV, Camarozano AC, Carmo DC, Sá CRF, Fortunato JA, Darwich RZ; Critical review of the manuscript for important intellectual content: Coimbra RM, Baroncini LAV, Camarozano AC.</p>
				</fn>
				<fn fn-type="conflict">
					<p><bold>Conflict of interest</bold></p>
					<p>The authors have declared that they have no conflict of interest.</p>
				</fn>
			</author-notes>
			<pub-date date-type="pub" publication-format="electronic">
				<day>30</day>
				<month>03</month>
				<year>2022</year>
			</pub-date>
			<pub-date date-type="collection" publication-format="electronic">
				<year>2022</year>
			</pub-date>
			<volume>35</volume>
			<issue>1</issue>
			<elocation-id>eabc242</elocation-id>
			<history>
				<date date-type="received">
					<day>22</day>
					<month>08</month>
					<year>2021</year>
				</date>
				<date date-type="rev-recd">
					<day>09</day>
					<month>11</month>
					<year>2021</year>
				</date>
				<date date-type="accepted">
					<day>22</day>
					<month>02</month>
					<year>2022</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>Pulmonary artery acceleration time (PAAT) can be used as a parameter in the evaluation of pulmonary hypertension and aids left ventricular diastolic function (LVDF) analyses.</p>
				</sec>
				<sec>
					<title>Objective:</title>
					<p>To assess whether there is a correlation between PAAT and LVDF parameters in individuals with a preserved left ventricular systolic function and by sex, age, and cardiovascular risk factors.</p>
				</sec>
				<sec>
					<title>Methods:</title>
					<p>Observational cross-sectional study. One hundred nineteen patients were selected (59 women [49.6%]). The subjects underwent transthoracic echocardiography including measurements of PAAT, E and A waves and E/A ratio, e’ septal and e’ lateral waves and E/e’ ratio, pulmonary artery systolic pressure (PASP), and left atrial volume.</p>
				</sec>
				<sec>
					<title>Results:</title>
					<p>In female patients, a positive correlation (Spearman’s correlation coefficient – Spearman correlation coefficient [SCC]) was found between the PAAT value and the lateral e’ (SCC, 0.47; p = 0.002), with the E/A ratio (SCC, 0.32; p = 0.04), and with septal e’ (SCC, 0.36; p = 0.023), and a negative correlation between PAAT and PASP (SCC, -0.43; p = 0.034). In men, no correlation was found between PAAT and any parameters. Lower PAAT values were found in women with systemic arterial hypertension (hypertension) than in women without hypertension (0.13 ± 0.03 s versus 0.16 ± 0.03 s; p = 0.015).</p>
				</sec>
				<sec>
					<title>Conclusion:</title>
					<p>The present study showed a significant correlation between PAAT and some LVDF parameters in female patients only. Hypertension was correlated with lower PAAT values in women.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="en">
				<title>Keywords:</title>
				<kwd>Cardiac function</kwd>
				<kwd>Cardiovascular disease</kwd>
				<kwd>COVID-19</kwd>
				<kwd>Echocardiography</kwd>
				<kwd>SARS-CoV-2</kwd>
			</kwd-group>
			<counts>
				<fig-count count="8"/>
				<table-count count="6"/>
				<equation-count count="0"/>
				<ref-count count="24"/>
			</counts>
		</article-meta>
	</front>
	<body>
		<sec sec-type="intro">
			<title>Introduction</title>
			<p>Transthoracic echocardiography (TTE) is an important tool in the investigation of several pathologies affecting the heart that analyzes the interdependence between various cardiac structures with noninvasive precision, particularly the correlation between the systolic function of the left (LV) and right ventricles (RV).<sup><xref ref-type="bibr" rid="B1">1</xref></sup> However, the blood flow to the lungs and its correlation with the parameters that determine LV diastolic function (LVDF) have been poorly investigated.</p>
			<p>The RV outflow tract acceleration time, also called pulmonary artery acceleration time (PAAT), corresponds to the time the flow through the pulmonary valve takes to reach its maximum peak velocity estimated by spectral pulsed-wave Doppler in the RV outflow tract. This value is considered normal when &gt;120 ms and abnormal when &lt;105 ms,<sup><xref ref-type="bibr" rid="B2">2</xref> - <xref ref-type="bibr" rid="B4">4</xref></sup> suggesting the presence but not severity of pulmonary hypertension (PH). Although it is not as reliable as tricuspid regurgitation velocity, which more accurately estimates pulmonary artery systolic pressure (PASP), PAAT can also be used in this assessment.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
			<p>Assessing left ventricular diastolic dysfunction is a complex task based on several echocardiographic measurements and parameters, including PASP. This value cannot be estimated without adequate tricuspid regurgitation.<sup><xref ref-type="bibr" rid="B6">6</xref> - <xref ref-type="bibr" rid="B7">7</xref></sup> Therefore, the present study aimed to assess whether there is a correlation between PAAT and LVDF parameters in subjects with preserved LV systolic function in the absence of advanced LV diastolic dysfunction and by sex, age, and cardiovascular risk factors.</p>
		</sec>
		<sec sec-type="methods">
			<title>Methods</title>
			<sec>
				<title>Study population</title>
				<p>This was an observational cross-sectional study. A total of 119 patients aged over 18 years, including 59 women (49.6%), were selected regardless of ethnicity from the cardiology outpatient clinic of the Red Cross Hospital of Curitiba after being referred for TTE by the assistant physician for any clinical indication.</p>
				<p>The patients were selected by convenience, without statistical criteria, according to their availability to participate in the research. A protocol form with clinical and echocardiographic parameters was completed for each patient. The clinical data collected were age, sex, weight, height, body mass index (BMI), and presence of systemic arterial hypertension (SAH), diabetes mellitus (DM), coronary artery disease (CAD), smoking (current or previous), and dyslipidemia. SAH, DM, dyslipidemia, and smoking were listed in the patients’ medical records and/or reported by them. CAD was confirmed by the medical record review and the patient through a reported history of non-fatal myocardial infarction and surgical or percutaneous myocardial revascularization. Regularly used medications were also recorded.</p>
				<p>The exclusion criteria were a) significant valvular disease (moderate or severe); b) valve prostheses; c) segmental LV contraction changes due to ischemic heart disease or other cardiomyopathies; d) pulmonary emphysema or chronic obstructive pulmonary disease; e) moderate to severe pulmonary arterial hypertension (PASP &gt; 50 mmHg); f) left ventricular contractile dysfunction (ejection fraction &lt; 52% for men and &lt; 54% for women); g) infiltrative and pericardial diseases; h) congenital heart disease with increased pulmonary blood flow with or without surgical correction; i) pacemaker; j) atrial fibrillation; and k) advanced (II and III) LV diastolic dysfunction.</p>
				<p>The patients underwent complete two-dimensional TTE using Phillips IE 33, Envisor or General Electric Vivid E echocardiography equipment. All acoustic windows and all standard echocardiographic measurements and analyses were performed for each patient. Sonographic measurements were performed by two experienced echocardiographers qualified in echocardiography by the Department of Cardiovascular Imaging of the Brazilian Society of Cardiology.</p>
				<p>All patients signed an informed consent form. The study was approved by the institution’s research ethics committee.</p>
			</sec>
			<sec>
				<title>Main echocardiographic parameters analyzed in this study</title>
				<p>The following parameters were examined: E and A waves and E/A ratio on spectral pulsed-wave Doppler of the mitral inflow; Septal and lateral e’ waves and E/e’ ratio (E wave/average between septal and lateral e’ velocities) on pulsed tissue Doppler of the mitral annulus; PASP (mmHg) through the maximum tricuspid regurgitation velocity (m/s), when present, on continuous spectral wave Doppler of tricuspid regurgitation, and inferior vena cava diameter (mm); PAAT measured immediately above the pulmonary valve leaflets on spectral pulsed-wave Doppler of the RV outflow tract ( <xref ref-type="fig" rid="f1">Figures 1</xref> and <xref ref-type="fig" rid="f2">2</xref> ); Indexed left atrial volume (normal up to 34 mL/m² for women and men) measured using the modified biplane Simpson’s method in four- and two-chamber orthogonal projections.</p>
				<fig id="f1">
					<label>Figure 1</label>
					<caption>
						<title>Parasternal cross-sectional view at the level of the base vessels. The figure shows the pulsed-wave Doppler cursor positioned on the right ventricular outflow tract used to obtain the PAAT.</title>
					</caption>
					<graphic xlink:href="0102-762X-dic-35-1-eabc242-gf01.tif"/>
				</fig>
				<fig id="f2">
					<label>Figure 2</label>
					<caption>
						<title>Pulsed-wave Doppler PAAT scan.</title>
					</caption>
					<graphic xlink:href="0102-762X-dic-35-1-eabc242-gf02.tif"/>
				</fig>
				<p>All quantifications and values considered in the present study were based on American Society of Echocardiography and European Society of Cardiovascular Imaging guidelines.<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B10">10</xref></sup></p>
			</sec>
			<sec>
				<title>Statistical analysis</title>
				<p>The women and men were analyzed separately. The study results are described as mean, median, minimum and maximum value, and standard deviation for quantitative variables or as frequency and percentage for categorical variables. The association between two quantitative variables was estimated by the Pearson or Spearman correlation coefficient (PCC and SCC, respectively). Quantitative variables were compared using Student’s t-test for independent samples or the non-parametric Mann-Whitney test. More than two groups were compared using one-way analysis of variance and the least significant difference test for multiple comparisons or the non-parametric Kruskal-Wallis test. The normality of the variables was evaluated by the Kolmogorov-Smirnov test. P values &lt; 0.05 were considered statistically significant.</p>
				<p>The data were analyzed using SPSS Statistics software v.20.0 (IBM Corp., Armonk, NY, USA).</p>
			</sec>
		</sec>
		<sec sec-type="results">
			<title>Results</title>
			<p>The final analysis included 119 subjects, 59 (49.6%) women (62.6 ± 16.5 years) and 60 (50.4%) men (65.1 ± 11.2 years). The clinical and epidemiological characteristics of the studied population are shown in <xref ref-type="table" rid="t1">Table 1</xref> . The baseline echocardiographic parameters of the studied population agreed with the literature.<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B10">10</xref></sup><xref ref-type="table" rid="t2"/>
			</p>
			<table-wrap id="t1">
				<label>Table 1</label>
				<caption>
					<title>Basic characteristics of the study population.</title>
				</caption>
				<table frame="hsides" rules="groups">
					<colgroup width="20%">
						<col/>
						<col/>
						<col/>
						<col/>
						<col/>
					</colgroup>
					<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
						<tr>
							<th align="center" valign="middle">Variable</th>
							<th align="center" valign="middle">n</th>
							<th align="center" valign="middle">Women</th>
							<th align="center" valign="middle">n</th>
							<th align="center" valign="middle">Men</th>
						</tr>
					</thead>
					<tbody style="border-bottom: thin solid; border-color: #000000">
						<tr>
							<td align="left" valign="middle">Age, years</td>
							<td align="center" valign="middle">59</td>
							<td align="center" valign="middle">62.6 ± 16.5</td>
							<td align="center" valign="middle">60</td>
							<td align="center" valign="middle">65.1 ± 11.2</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>BMI</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">&lt;30</td>
							<td align="center" valign="middle">41</td>
							<td align="center" valign="middle">72</td>
							<td align="center" valign="middle">41</td>
							<td align="center" valign="middle">68</td>
						</tr>
						<tr>
							<td align="left" valign="middle">≥30</td>
							<td align="center" valign="middle">16</td>
							<td align="center" valign="middle">28</td>
							<td align="center" valign="middle">19</td>
							<td align="center" valign="middle">32</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>SAH</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Yes</td>
							<td align="center" valign="middle">37</td>
							<td align="center" valign="middle">68</td>
							<td align="center" valign="middle">39</td>
							<td align="center" valign="middle">70</td>
						</tr>
						<tr>
							<td align="left" valign="middle">No</td>
							<td align="center" valign="middle">17</td>
							<td align="center" valign="middle">32</td>
							<td align="center" valign="middle">17</td>
							<td align="center" valign="middle">30</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>Dyslipidemia</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Yes</td>
							<td align="center" valign="middle">24</td>
							<td align="center" valign="middle">44</td>
							<td align="center" valign="middle">15</td>
							<td align="center" valign="middle">27</td>
						</tr>
						<tr>
							<td align="left" valign="middle">No</td>
							<td align="center" valign="middle">30</td>
							<td align="center" valign="middle">56</td>
							<td align="center" valign="middle">41</td>
							<td align="center" valign="middle">73</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>DM</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Yes</td>
							<td align="center" valign="middle">20</td>
							<td align="center" valign="middle">37</td>
							<td align="center" valign="middle">16</td>
							<td align="center" valign="middle">29</td>
						</tr>
						<tr>
							<td align="left" valign="middle">No</td>
							<td align="center" valign="middle">34</td>
							<td align="center" valign="middle">63</td>
							<td align="center" valign="middle">40</td>
							<td align="center" valign="middle">71</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>CAD</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Yes</td>
							<td align="center" valign="middle">11</td>
							<td align="center" valign="middle">20</td>
							<td align="center" valign="middle">21</td>
							<td align="center" valign="middle">37</td>
						</tr>
						<tr>
							<td align="left" valign="middle">No</td>
							<td align="center" valign="middle">43</td>
							<td align="center" valign="middle">80</td>
							<td align="center" valign="middle">35</td>
							<td align="center" valign="middle">62</td>
						</tr>
					</tbody>
				</table>
				<table-wrap-foot>
					<fn id="TFN1">
						<p>BMI, body mass index; CAD, coronary artery disease; DM, diabetes mellitus; SAH, systemic arterial hypertension; SD, standard deviation.</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
			<table-wrap id="t2">
				<label>Table 2</label>
				<caption>
					<title>Echocardiographic and hemodynamic parameters of the study population.</title>
				</caption>
				<table frame="hsides" rules="groups">
					<colgroup width="20%">
						<col/>
						<col/>
						<col/>
						<col/>
						<col/>
					</colgroup>
					<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
						<tr>
							<th align="left" valign="middle">Variable</th>
							<th align="center" valign="middle">n</th>
							<th align="center" valign="middle">Mean</th>
							<th align="center" valign="middle">SD</th>
							<th align="center" valign="middle">p <xref ref-type="table-fn" rid="TFN2">*</xref>
							</th>
						</tr>
					</thead>
					<tbody style="border-bottom: thin solid; border-color: #000000">
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>E wave</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">45</td>
							<td align="center" valign="middle">0.75</td>
							<td align="center" valign="middle">0.27</td>
							<td align="center" rowspan="2" valign="middle">0.070</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">43</td>
							<td align="center" valign="middle">0.65</td>
							<td align="center" valign="middle">0.27</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>A wave</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">41</td>
							<td align="center" valign="middle">0.80</td>
							<td align="center" valign="middle">0.20</td>
							<td align="center" rowspan="2" valign="middle">0.484</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">39</td>
							<td align="center" valign="middle">0.77</td>
							<td align="center" valign="middle">0.24</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>E/A ratio</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">41</td>
							<td align="center" valign="middle">0.97</td>
							<td align="center" valign="middle">0.44</td>
							<td align="center" rowspan="2" valign="middle">0.234</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">39</td>
							<td align="center" valign="middle">0.92</td>
							<td align="center" valign="middle">0.65</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>Lateral e′ wave</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">43</td>
							<td align="center" valign="middle">0.10</td>
							<td align="center" valign="middle">0.04</td>
							<td align="center" rowspan="2" valign="middle">0.835</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">42</td>
							<td align="center" valign="middle">0.09</td>
							<td align="center" valign="middle">0.03</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>Septal e′ wave</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">43</td>
							<td align="center" valign="middle">0.08</td>
							<td align="center" valign="middle">0.03</td>
							<td align="center" rowspan="2" valign="middle">0.509</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">42</td>
							<td align="center" valign="middle">0.07</td>
							<td align="center" valign="middle">0.03</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>E/e′ ratio</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">43</td>
							<td align="center" valign="middle">10.0</td>
							<td align="center" valign="middle">4.7</td>
							<td align="center" rowspan="2" valign="middle">0.150</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">41</td>
							<td align="center" valign="middle">8.6</td>
							<td align="center" valign="middle">2.7</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>PASP</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">31</td>
							<td align="center" valign="middle">28.8</td>
							<td align="center" valign="middle">11.7</td>
							<td align="center" rowspan="2" valign="middle">0.346</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">29</td>
							<td align="center" valign="middle">29.7</td>
							<td align="center" valign="middle">9.0</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>AE volume</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">35</td>
							<td align="center" valign="middle">36.7</td>
							<td align="center" valign="middle">19.3</td>
							<td align="center" rowspan="2" valign="middle">0.772</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">42</td>
							<td align="center" valign="middle">35.1</td>
							<td align="center" valign="middle">14.0</td>
						</tr>
						<tr>
							<td align="left" colspan="5" valign="middle"><bold>PAAT</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">45</td>
							<td align="center" valign="middle">0.15</td>
							<td align="center" valign="middle">0.04</td>
							<td align="center" rowspan="2" valign="middle">0.404</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">37</td>
							<td align="center" valign="middle">0,14</td>
							<td align="center" valign="middle">0,03</td>
						</tr>
					</tbody>
				</table>
				<table-wrap-foot>
					<fn id="TFN2">
						<label>*</label>
						<p>Student’s t-test for independent samples or non-parametric Mann-Whitney test, p &lt; 0.05. LA, left atrium; PAAT, pulmonary artery acceleration time; PASP, pulmonary artery systolic pressure; SD, standard deviation.</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
			<p>Women showed a positive and significant correlation between PAAT and lateral e’ (SCC, 0.47; p = 0.002), E/A ratio (SCC, 0.32; p = 0.04), and septal e’ (SCC, 0.36; p = 0.023); and a negative correlation between PAAT and PASP (SCC -0.43; p = 0.034), ( <xref ref-type="fig" rid="f3">Figures 3</xref> and <xref ref-type="fig" rid="f4">4</xref> ). The other variables were not correlated with PAAT, and the male participants showed no significant correlation with the analyzed parameters ( <xref ref-type="table" rid="t3">Table 3</xref> ).</p>
			<fig id="f3">
				<label>Figure 3</label>
				<caption>
					<title>Correlation between pulmonary artery acceleration time (PAAT) and lateral E′ and medial e′ waves in women.</title>
				</caption>
				<graphic xlink:href="0102-762X-dic-35-1-eabc242-gf03.tif"/>
			</fig>
			<fig id="f4">
				<label>Figure 4</label>
				<caption>
					<title>Correlation between pulmonary artery acceleration time (PAAT), E/A ratio, and pulmonary artery systolic pressure (PASP).</title>
				</caption>
				<graphic xlink:href="0102-762X-dic-35-1-eabc242-gf04.tif"/>
			</fig>
			<table-wrap id="t3">
				<label>Table 3</label>
				<caption>
					<title>Correlation between PAAT and diastolic function parameters.</title>
				</caption>
				<table frame="hsides" rules="groups">
					<colgroup width="25%">
						<col/>
						<col/>
						<col/>
						<col/>
					</colgroup>
					<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
						<tr>
							<th align="center" valign="middle">Variable</th>
							<th align="center" valign="middle">n</th>
							<th align="center" valign="middle">r</th>
							<th align="center" valign="middle">p</th>
						</tr>
					</thead>
					<tbody style="border-bottom: thin solid; border-color: #000000">
						<tr>
							<td align="left" colspan="4" valign="middle"><bold>PAAT × E/A ratio</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">41</td>
							<td align="center" valign="middle">0.32</td>
							<td align="center" valign="middle">0.040</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">35</td>
							<td align="center" valign="middle">0.32</td>
							<td align="center" valign="middle">0.061</td>
						</tr>
						<tr>
							<td align="left" colspan="4" valign="middle"><bold>PAAT × septal e′ wave</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">40</td>
							<td align="center" valign="middle">0.36</td>
							<td align="center" valign="middle">0.023</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">35</td>
							<td align="center" valign="middle">0.30</td>
							<td align="center" valign="middle">0.081</td>
						</tr>
						<tr>
							<td align="left" colspan="4" valign="middle"><bold>PAAT × E/e′ ratio</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">40</td>
							<td align="center" valign="middle">-0.13</td>
							<td align="center" valign="middle">0.436</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">35</td>
							<td align="center" valign="middle">-0.04</td>
							<td align="center" valign="middle">0.822</td>
						</tr>
						<tr>
							<td align="left" colspan="4" valign="middle"><bold>PAAT × PASP</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">25</td>
							<td align="center" valign="middle">-0.43</td>
							<td align="center" valign="middle">0.034</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">19</td>
							<td align="center" valign="middle">-0.21</td>
							<td align="center" valign="middle">0.380</td>
						</tr>
						<tr>
							<td align="left" colspan="4" valign="middle"><bold>PAAT × LAV</bold></td>
						</tr>
						<tr>
							<td align="left" valign="middle">Female</td>
							<td align="center" valign="middle">28</td>
							<td align="center" valign="middle">-0.08</td>
							<td align="center" valign="middle">0.701</td>
						</tr>
						<tr>
							<td align="left" valign="middle">Male</td>
							<td align="center" valign="middle">29</td>
							<td align="center" valign="middle">-0.11</td>
							<td align="center" valign="middle">0.577</td>
						</tr>
					</tbody>
				</table>
				<table-wrap-foot>
					<fn id="TFN3">
						<p>LAV, left atrial volume; PAAT, pulmonary artery acceleration time; PASP, pulmonary artery systolic pressure; r, Spearman correlation coefficient.</p>
					</fn>
				</table-wrap-foot>
			</table-wrap>
			<p>PAAT was not influenced by sex, BMI, DM, dyslipidemia, CAD, or smoking (data not shown). However, lower PAAT values were found in women with versus without SAH (0.13 ± 0.03 versus 0.16 ± 0.03 s, respectively; p = 0.015).</p>
			<p> Age was not significantly correlated with PAAT in either sex (SCC, -0.27, p = 0.068 for women; SCC, -0.31, p = 0.065 for men).</p>
		</sec>
		<sec sec-type="discussion">
			<title>Discussion</title>
			<p>The present study found a significant positive correlation between PAAT and LVDF parameters (septal and lateral e’ waves and E/A ratio) in women only, in whom the presence of SAH was associated with a lower PAAT. However, the general analysis of the studied population showed no significant PAAT differences in sex, age, or BMI.</p>
			<p>PASP is currently the most commonly used PH data in LVDF assessments. PH degree is usually assessed by PASP estimated by tricuspid valve regurgitation. PAAT has a negative correlation with PASP (data also found in the present study). According to Granstam et al.,<sup><xref ref-type="bibr" rid="B11">11</xref></sup> tricuspid regurgitation may not be present or be unreliable for the correct estimation of PASP during TTE examinations. Considering this, they estimated pulmonary vascular resistance invasively, correlating it with PAAT values as a possible alternative for identifying PH. Therefore, considering those findings, it is important to have more than one method available to estimate PH in an LVDF study, especially when it is not possible to reliably estimate tricuspid regurgitation or in early cases of diastolic dysfunction that lack a significantly increased pulmonary pressure. In cases of preserved LV systolic function, the differentiation between normal and abnormal diastolic function becomes complicated due to overlapped indices obtained by Doppler. Although age structurally changes the heart and the vessels, the analysis of healthy older people by Doppler showed similar values to those of younger age groups (40–60 years of age).<sup><xref ref-type="bibr" rid="B12">12</xref></sup> Considering the mean age of the studied population (relatively young subjects) and that all had preserved LV systolic function, no significant differences were expected in the parameters evaluated by Doppler. However, we expected that the inclusion of PAAT values could differentiate between early stages of diastolic dysfunction when PASP is not extremely high.</p>
			<p>A study by Baroncini et al.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> of 87 participants also showed a negative correlation between PAAT and age and a positive correlation between PAAT and E/A ratio with no significance between other variables or the sexes. This study demonstrated that PAAT values &lt; 0.135 s were associated with grade I diastolic dysfunction, while those &gt; 0.135 s were associated with normal diastole. These studies suggest that PAAT correlates with parameters used to assess LVDF, even in the early stages when there are no signs of significant pulmonary arterial hypertension. At this stage, the E/e’ ratio is still low and the PAAT values are within the normal range (&gt;120 ms).<sup><xref ref-type="bibr" rid="B14">14</xref> , <xref ref-type="bibr" rid="B15">15</xref></sup></p>
			<p>In a study of a larger number of participants, Marra et al.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> analyzed 1,029 healthy subjects and reported no differences in PAAT values between men and women. However, they noticed a small reduction in this parameter with advancing age, increasing BMI, and higher systolic and diastolic systemic blood pressure. Similar to our findings, they also found a positive correlation between PAAT and E/A ratio; however, they did not discuss this last finding, suggesting the need for further studies in the area.</p>
			<p>A study by Zabalgoitia et al.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> prospectively analyzed LV mass, relative wall thickness, and systolic and diastolic interaction in 508 hypertensive patients aged 50–80 years according to age and sex. In men, most measures were similarly distributed. Nevertheless, women aged 65 years and older presented smaller LV systolic dimensions, greater ventricular thicknesses, greater fractional shortening, and less end-systolic wall stress, i.e., structural and functional changes were more pronounced in women.</p>
			<p>In the present study, statistically significant findings, particularly in women, correlated with the findings by Zabalgoitia et al.,<sup><xref ref-type="bibr" rid="B17">17</xref></sup> indicating the importance of further studies on systolic ventricular function, diastolic function, possible hormonal influence, and SAH behavior in the female heart. Previous studies already reported hormonal influence in pre- and postmenopausal women and a higher incidence of heart failure with preserved ejection fraction in women.<sup><xref ref-type="bibr" rid="B18">18</xref> , <xref ref-type="bibr" rid="B19">19</xref></sup> Likewise, SAH causes different structural changes in ventricular geometric patterns in men and women, with possible deleterious effects that are more pronounced in women.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
			<p>A study by Alecrin et al.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> with postmenopausal hypertensive women showed that hormone replacement therapy with oral estradiol for 12 weeks significantly improved LVDF on TTE. Mohamed et al.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> correlated diastolic dysfunction with age and arterial hypertension and concluded that arterial hypertension duration, systolic and diastolic arterial hypertension level, and age are important prognostic indicators for predicting the development of diastolic dysfunction in hypertensive patients. A better understanding of these particularities may improve the treatment of hypertension and congestive heart failure.</p>
			<p>Liebson et al.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> evaluated a large population of men (n=511) and women (n=333) with mild primary hypertension and found a substantial percentage of participants with left ventricular hypertrophy diagnosed on echocardiography. In that study, left ventricular mass indices were positively correlated with systolic blood pressure, BMI, urinary sodium excretion, and smoking, with no significant difference between the sexes. Also, similar to findings presented here, they found a positive correlation between the PAAT and E/A ratio, without, however, discussing the later finding, suggesting further studies in this area.</p>
			<p>The main limitation of the present study is the small number of participants (N=119), especially compared to other studies, thus increasing the chances of outliers that may have influenced the final results presented here. Another relevant factor was the exclusion of patients with more advanced degrees of diastolic dysfunction (DD), hindering the assessment of PAAT behavior in these situations. However, the main objective was to evaluate PAAT behavior in the initial stages of left ventricular DD. Echocardiographic measurement intra- and inter-observer variability is also possible,<sup><xref ref-type="bibr" rid="B24">24</xref></sup> but this analysis was not performed in the parameters evaluated here. However, none of the studies cited in the discussion presented this PAAT analysis. Likewise, heart rate and blood pressure were also not measured concomitantly. According to Marra et al.,<sup><xref ref-type="bibr" rid="B16">16</xref></sup> who analyzed eight previous studies with 1,029 healthy subjects, PAAT values were weakly influenced by both heart rate and blood pressure.</p>
		</sec>
		<sec sec-type="conclusions">
			<title>Conclusions</title>
			<p>The present study correlated PAAT with signs of early left ventricular DD in women only. Among the cardiovascular risk factors, the presence of SAH influenced PAAT in women only.</p>
		</sec>
	</body>
	<back>
		<ref-list>
			<title>References</title>
			<ref id="B1">
				<label>1</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Bruhl</surname>
							<given-names>SR</given-names>
						</name>
						<name>
							<surname>Chahal</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Khouri</surname>
							<given-names>SJ</given-names>
						</name>
					</person-group>
					<article-title>A novel approach to standard techniques in the assessment and quantification of the interventricular systolic relationship</article-title>
					<source>Cardiovasc Ultrasound</source>
					<year>2011</year>
					<volume>9</volume>
					<fpage>42</fpage>
					<lpage>42</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1186/1476-7120-9-42">https://doi.org/10.1186/1476-7120-9-42</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>1 Bruhl SR, Chahal M, Khouri SJ. A novel approach to standard techniques in the assessment and quantification of the interventricular systolic relationship. Cardiovasc Ultrasound. 2011;9:42. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1186/1476-7120-9-42">https://doi.org/10.1186/1476-7120-9-42</ext-link>.</mixed-citation>
			</ref>
			<ref id="B2">
				<label>2</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Yared</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>Noseworthy</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Weyman</surname>
							<given-names>AE</given-names>
						</name>
						<name>
							<surname>McCabe</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Picard</surname>
							<given-names>MH</given-names>
						</name>
						<name>
							<surname>Baggish</surname>
							<given-names>AL</given-names>
						</name>
					</person-group>
					<article-title>Pulmonary artery acceleration time provides an accurate estimate of systolic pulmonary arterial pressure during transthoracic echocardiography</article-title>
					<source>J Am Soc Echocardiogr</source>
					<year>2011</year>
					<volume>24</volume>
					<issue>6</issue>
					<fpage>687</fpage>
					<lpage>692</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.echo.2011.03.008">https://doi.org/10.1016/j.echo.2011.03.008</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>2 Yared K, Noseworthy P, Weyman AE, McCabe E, Picard MH, Baggish AL. Pulmonary artery acceleration time provides an accurate estimate of systolic pulmonary arterial pressure during transthoracic echocardiography. J Am Soc Echocardiogr. 2011;24(6):687-92. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.echo.2011.03.008">https://doi.org/10.1016/j.echo.2011.03.008</ext-link>.</mixed-citation>
			</ref>
			<ref id="B3">
				<label>3</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lopez-Candales</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Eleswarapu</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Shaver</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Edelman</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>Gulyasy</surname>
							<given-names>B</given-names>
						</name>
						<etal/>
					</person-group>
					<article-title>Right ventricular outflow tract spectral signal: a useful marker of right ventricular systolic performance and pulmonary hypertension severity</article-title>
					<source>Eur J Echocardiogr</source>
					<year>2010</year>
					<month>07</month>
					<volume>11</volume>
					<issue>6</issue>
					<fpage>509</fpage>
					<lpage>515</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1093/ejechocard/jeq009">https://doi.org/1010.1093/ejechocard/jeq009</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>3 Lopez-Candales A, Eleswarapu A, Shaver J, Edelman K, Gulyasy B, et al. Right ventricular outflow tract spectral signal: a useful marker of right ventricular systolic performance and pulmonary hypertension severity. Eur J Echocardiogr. 2010 Jul;11(6):509-15. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1093/ejechocard/jeq009">https://doi.org/1010.1093/ejechocard/jeq009</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B4">
				<label>4</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Grapsa</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Tzemos</surname>
							<given-names>N</given-names>
						</name>
					</person-group>
					<article-title>Echocardiography in pulmonar hypertension: current evidence and future perspectives</article-title>
					<source>Continuing Cardiology Education</source>
					<year>2018</year>
					<volume>3</volume>
					<fpage>4</fpage>
					<lpage>4</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1002/cce2.67">https://doi.org/10.1002/cce2.67</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>4 Grapsa J, Tzemos N. Echocardiography in pulmonar hypertension: current evidence and future perspectives. Continuing Cardiology Education. 2018;3:4. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1002/cce2.67">https://doi.org/10.1002/cce2.67</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B5">
				<label>5</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Sbano</surname>
							<given-names>JC</given-names>
						</name>
						<name>
							<surname>Tsutsui</surname>
							<given-names>JM</given-names>
						</name>
						<name>
							<surname>Terra</surname>
							<given-names>M</given-names>
							<suffix>Filho</suffix>
						</name>
						<name>
							<surname>Mathias</surname>
							<given-names>W</given-names>
							<suffix>Junior</suffix>
						</name>
					</person-group>
					<article-title>Papel da ecodopplercardiografia na avaliação da hipertensão arterial pulmonar</article-title>
					<source>J Bras Pneumol</source>
					<year>2004</year>
					<volume>30</volume>
					<issue>1</issue>
					<fpage>78</fpage>
					<lpage>86</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1590/S1806-37132004000100014">https://doi.org/10.1590/S1806-37132004000100014</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>5 Sbano JC, Tsutsui JM, Terra-Filho M, Mathias Junior W. Papel da ecodopplercardiografia na avaliação da hipertensão arterial pulmonar. J Bras Pneumol. 2004;30(1):78-86. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1590/S1806-37132004000100014">https://doi.org/10.1590/S1806-37132004000100014</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B6">
				<label>6</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Little</surname>
							<given-names>WC</given-names>
						</name>
						<name>
							<surname>Downes</surname>
							<given-names>TR</given-names>
						</name>
					</person-group>
					<article-title>Clinical evaluation of left ventricular diastolic performance</article-title>
					<source>Prog Cardiovasc Dis</source>
					<year>1990</year>
					<volume>32</volume>
					<issue>4</issue>
					<fpage>273</fpage>
					<lpage>290</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/0033-0620(90)90017-v">https://doi.org/1010.1016/0033-0620(90)90017-v</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>6 Little WC, Downes TR. Clinical evaluation of left ventricular diastolic performance. Prog Cardiovasc Dis. 1990;32(4):273-90. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/0033-0620(90)90017-v">https://doi.org/1010.1016/0033-0620(90)90017-v</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B7">
				<label>7</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Mirsky</surname>
							<given-names>I</given-names>
						</name>
						<name>
							<surname>Pasipoularides</surname>
							<given-names>A</given-names>
						</name>
					</person-group>
					<article-title>Clinical assessment of diastolic function</article-title>
					<source>Prog Cardiovasc Dis</source>
					<year>1990</year>
					<volume>32</volume>
					<issue>4</issue>
					<fpage>291</fpage>
					<lpage>318</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/0033-0620(90)90018-w">https://doi.org/1010.1016/0033-0620(90)90018-w</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>7 Mirsky I, Pasipoularides A. Clinical assessment of diastolic function. Prog Cardiovasc Dis. 1990;32(4):291-318. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/0033-0620(90)90018-w">https://doi.org/1010.1016/0033-0620(90)90018-w</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B8">
				<label>8</label>
				<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/>
					</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.e14</fpage>
					<lpage>39.e14</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.echo.2014.10.003">https://doi.org/1010.1016/j.echo.2014.10.003</ext-link>
					</comment>
				</element-citation>
				<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: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.echo.2014.10.003">https://doi.org/1010.1016/j.echo.2014.10.003</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B9">
				<label>9</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>DiLorenzo</surname>
							<given-names>MP</given-names>
						</name>
						<name>
							<surname>Bhatt</surname>
							<given-names>SM</given-names>
						</name>
						<name>
							<surname>Mercer-Rosa</surname>
							<given-names>L</given-names>
						</name>
					</person-group>
					<article-title>How best to assess right ventricular function by echocardiography</article-title>
					<source>Cardiol Young</source>
					<year>2015</year>
					<volume>25</volume>
					<issue>8</issue>
					<fpage>1473</fpage>
					<lpage>1481</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1017/S1047951115002255">https://doi.org/1010.1017/S1047951115002255</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>9 DiLorenzo MP, Bhatt SM, Mercer-Rosa L. How best to assess right ventricular function by echocardiography. Cardiol Young. 2015;25(8):1473-81. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1017/S1047951115002255">https://doi.org/1010.1017/S1047951115002255</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B10">
				<label>10</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Rudski</surname>
							<given-names>LG</given-names>
						</name>
						<name>
							<surname>Lai</surname>
							<given-names>WW</given-names>
						</name>
						<name>
							<surname>Afilalo</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Hua</surname>
							<given-names>L</given-names>
						</name>
						<name>
							<surname>Handschumacher</surname>
							<given-names>MD</given-names>
						</name>
						<name>
							<surname>Chandrasekaran</surname>
							<given-names>K</given-names>
						</name>
						<etal/>
					</person-group>
					<article-title>Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography</article-title>
					<source>J Am Soc Echocardiogr</source>
					<year>2010</year>
					<volume>23</volume>
					<issue>7</issue>
					<fpage>685</fpage>
					<lpage>713</lpage>
					<comment>quiz 786-8</comment>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.echo.2010.05.010">https://doi.org/1010.1016/j.echo.2010.05.010</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>10 Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685-713; quiz 786-8. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.echo.2010.05.010">https://doi.org/1010.1016/j.echo.2010.05.010</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B11">
				<label>11</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Granstam</surname>
							<given-names>SO</given-names>
						</name>
						<name>
							<surname>Björklund</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Wikström</surname>
							<given-names>G</given-names>
						</name>
						<name>
							<surname>Roos</surname>
							<given-names>MW</given-names>
						</name>
					</person-group>
					<article-title>Use of echocardiographic pulmonary acceleration time and estimated vascular resistance for the evaluation of possible pulmonary hypertension</article-title>
					<source>Cardiovasc Ultrasound</source>
					<year>2013</year>
					<volume>11</volume>
					<fpage>7</fpage>
					<lpage>7</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1186/1476-7120-11-7">https://doi.org/1010.1186/1476-7120-11-7</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>11 Granstam SO, Björklund E, Wikström G, Roos MW. Use of echocardiographic pulmonary acceleration time and estimated vascular resistance for the evaluation of possible pulmonary hypertension. Cardiovasc Ultrasound. 2013;11:7. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1186/1476-7120-11-7">https://doi.org/1010.1186/1476-7120-11-7</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B12">
				<label>12</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Nagueh</surname>
							<given-names>SF</given-names>
						</name>
						<name>
							<surname>Smiseth</surname>
							<given-names>OA</given-names>
						</name>
						<name>
							<surname>Appleton</surname>
							<given-names>CP</given-names>
						</name>
						<name>
							<surname>Byrd</surname>
							<given-names>BF</given-names>
							<suffix>3rd</suffix>
						</name>
						<name>
							<surname>Dokainish</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Edvardsen</surname>
							<given-names>T</given-names>
						</name>
						<etal/>
					</person-group>
					<article-title>Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging</article-title>
					<source>J Am Soc Echocardiogr</source>
					<year>2016</year>
					<volume>29</volume>
					<issue>4</issue>
					<fpage>277</fpage>
					<lpage>314</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.echo.2016.01.011">https://doi.org/1010.1016/j.echo.2016.01.011</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>12 Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29(4):277-314. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.echo.2016.01.011">https://doi.org/1010.1016/j.echo.2016.01.011</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B13">
				<label>13</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Baroncini</surname>
							<given-names>LA</given-names>
						</name>
						<name>
							<surname>Urnau</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>Camarozano</surname>
							<given-names>AC</given-names>
						</name>
						<name>
							<surname>Carmo</surname>
							<given-names>DC</given-names>
						</name>
						<name>
							<surname>Fortunato</surname>
							<given-names>JA</given-names>
						</name>
						<name>
							<surname>Darwich</surname>
							<given-names>RZ</given-names>
						</name>
					</person-group>
					<article-title>Rigth ventricle Outflow Tract Acceleration Time: Correlation with Left Ventricular Diastolic Function</article-title>
					<source>J Clinical Imaging and Intervencional Radiology</source>
					<year>2020</year>
					<volume>2</volume>
					<issue>1</issue>
					<fpage>1</fpage>
					<lpage>5</lpage>
				</element-citation>
				<mixed-citation>13 Baroncini LA, Urnau K, Camarozano AC, Carmo DC, Fortunato JA, Darwich RZ. Rigth ventricle Outflow Tract Acceleration Time: Correlation with Left Ventricular Diastolic Function. J Clinical Imaging and Intervencional Radiology. 2020;2(1):1-5.</mixed-citation>
			</ref>
			<ref id="B14">
				<label>14</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Kadappu</surname>
							<given-names>KK</given-names>
						</name>
						<name>
							<surname>Thomas</surname>
							<given-names>L</given-names>
						</name>
					</person-group>
					<article-title>Tissue Doppler imaging in echocardiography: value and limitations</article-title>
					<source>Heart Lung Circ</source>
					<year>2015</year>
					<volume>24</volume>
					<issue>3</issue>
					<fpage>224</fpage>
					<lpage>233</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.hlc.2014.10.003">https://doi.org/1010.1016/j.hlc.2014.10.003</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>14 Kadappu KK, Thomas L. Tissue Doppler imaging in echocardiography: value and limitations. Heart Lung Circ. 2015;24(3):224-33. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.hlc.2014.10.003">https://doi.org/1010.1016/j.hlc.2014.10.003</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B15">
				<label>15</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Zhang</surname>
							<given-names>W</given-names>
						</name>
						<name>
							<surname>Kovács</surname>
							<given-names>SJ</given-names>
						</name>
					</person-group>
					<article-title>The age dependence of left ventricular filling efficiency</article-title>
					<source>Ultrasound Med Biol</source>
					<year>2009</year>
					<volume>35</volume>
					<issue>7</issue>
					<fpage>1076</fpage>
					<lpage>1085</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.ultrasmedbio.2009.01.009">https://doi.org/1010.1016/j.ultrasmedbio.2009.01.009</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>15 Zhang W, Kovács SJ. The age dependence of left ventricular filling efficiency. Ultrasound Med Biol. 2009;35(7):1076-85. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.ultrasmedbio.2009.01.009">https://doi.org/1010.1016/j.ultrasmedbio.2009.01.009</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B16">
				<label>16</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Marra</surname>
							<given-names>AM</given-names>
						</name>
						<name>
							<surname>Benjamin</surname>
							<given-names>N</given-names>
						</name>
						<name>
							<surname>Ferrara</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Vriz</surname>
							<given-names>O</given-names>
						</name>
						<name>
							<surname>D’Alto</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>D’Andrea</surname>
							<given-names>A</given-names>
						</name>
						<etal/>
					</person-group>
					<article-title>Reference ranges and determinants of right ventricle outflow tract acceleration time in healthy adults by two-dimensional echocardiography</article-title>
					<source>Int J Cardiovasc Imaging</source>
					<year>2017</year>
					<volume>33</volume>
					<issue>2</issue>
					<fpage>219</fpage>
					<lpage>226</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1007/s10554-016-0991-0">https://doi.org/1010.1007/s10554-016-0991-0</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>16 Marra AM, Benjamin N, Ferrara F, Vriz O, D’Alto M, D’Andrea A, et al. Reference ranges and determinants of right ventricle outflow tract acceleration time in healthy adults by two-dimensional echocardiography. Int J Cardiovasc Imaging. 2017;33(2):219-26. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1007/s10554-016-0991-0">https://doi.org/1010.1007/s10554-016-0991-0</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B17">
				<label>17</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Zabalgoitia</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Rahman</surname>
							<given-names>SN</given-names>
						</name>
						<name>
							<surname>Haley</surname>
							<given-names>WE</given-names>
						</name>
						<name>
							<surname>Mercado</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Yunis</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Lucas</surname>
							<given-names>C</given-names>
						</name>
						<etal/>
					</person-group>
					<article-title>Comparison in systemic hypertension of left ventricular mass and geometry with systolic and diastolic function in patients &lt;65 to &gt; or = 65 years of age</article-title>
					<source>Am J Cardiol</source>
					<year>1998</year>
					<volume>82</volume>
					<issue>5</issue>
					<fpage>604</fpage>
					<lpage>608</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/s0002-9149(98)00404-4">https://doi.org/1010.1016/s0002-9149(98)00404-4</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>17 Zabalgoitia M, Rahman SN, Haley WE, Mercado R, Yunis C, Lucas C, et al. Comparison in systemic hypertension of left ventricular mass and geometry with systolic and diastolic function in patients &lt;65 to &gt; or = 65 years of age. Am J Cardiol. 1998;82(5):604-8. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/s0002-9149(98)00404-4">https://doi.org/1010.1016/s0002-9149(98)00404-4</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B18">
				<label>18</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Hirokawa</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Daimon</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Lee</surname>
							<given-names>SL</given-names>
						</name>
						<name>
							<surname>Nakao</surname>
							<given-names>T</given-names>
						</name>
						<name>
							<surname>Kawata</surname>
							<given-names>T</given-names>
						</name>
						<name>
							<surname>Kimura</surname>
							<given-names>K</given-names>
						</name>
						<etal/>
					</person-group>
					<article-title>Early menopause does not influence left ventricular diastolic dysfunction: A clinical observational study in healthy subjects</article-title>
					<source>J Cardiol</source>
					<year>2016</year>
					<volume>68</volume>
					<issue>6</issue>
					<fpage>548</fpage>
					<lpage>553</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.jjcc.2015.11.014">https://doi.org/1010.1016/j.jjcc.2015.11.014</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>18 Hirokawa M, Daimon M, Lee SL, Nakao T, Kawata T, Kimura K, et al. Early menopause does not influence left ventricular diastolic dysfunction: A clinical observational study in healthy subjects. J Cardiol. 2016;68(6):548-553. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1016/j.jjcc.2015.11.014">https://doi.org/1010.1016/j.jjcc.2015.11.014</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B19">
				<label>19</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Zhao</surname>
							<given-names>Z</given-names>
						</name>
						<name>
							<surname>Wang</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Jessup</surname>
							<given-names>JA</given-names>
						</name>
						<name>
							<surname>Lindsey</surname>
							<given-names>SH</given-names>
						</name>
						<name>
							<surname>Chappell</surname>
							<given-names>MC</given-names>
						</name>
						<name>
							<surname>Groban</surname>
							<given-names>L</given-names>
						</name>
					</person-group>
					<article-title>Role of estrogen in diastolic dysfunction</article-title>
					<source>Am J Physiol Heart Circ Physiol</source>
					<year>2014</year>
					<volume>306</volume>
					<issue>5</issue>
					<fpage>H628</fpage>
					<lpage>H640</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1152/ajpheart.00859.2013">https://doi.org/1010.1152/ajpheart.00859.2013</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>19 Zhao Z, Wang H, Jessup JA, Lindsey SH, Chappell MC, Groban L. Role of estrogen in diastolic dysfunction. Am J Physiol Heart Circ Physiol. 2014;306(5):H628-40. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1152/ajpheart.00859.2013">https://doi.org/1010.1152/ajpheart.00859.2013</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B20">
				<label>20</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Argemiro</surname>
							<given-names>AJ</given-names>
						</name>
						<name>
							<surname>Camarozano</surname>
							<given-names>AC</given-names>
						</name>
						<name>
							<surname>Carmo</surname>
							<given-names>DC</given-names>
						</name>
						<name>
							<surname>Fortunato</surname>
							<given-names>JA</given-names>
						</name>
						<name>
							<surname>Darwich</surname>
							<given-names>RZ</given-names>
						</name>
						<name>
							<surname>Baroncini</surname>
							<given-names>LA</given-names>
						</name>
					</person-group>
					<article-title>Hipertensão arterial sistêmica e ventrículo direito: dados ecocardiográficos preliminares</article-title>
					<source>Arq Bras Cardiol: Imagem Cardiovasc</source>
					<year>2018</year>
					<volume>31</volume>
					<fpage>268</fpage>
					<lpage>276</lpage>
				</element-citation>
				<mixed-citation>20 Argemiro AJ, Camarozano AC, Carmo DC, Fortunato JA, Darwich RZ, Baroncini LA. Hipertensão arterial sistêmica e ventrículo direito: dados ecocardiográficos preliminares. Arq Bras Cardiol: Imagem Cardiovasc. 2018;31:268-76.</mixed-citation>
			</ref>
			<ref id="B21">
				<label>21</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Alecrin</surname>
							<given-names>IN</given-names>
						</name>
						<name>
							<surname>Aldrighi</surname>
							<given-names>JM</given-names>
						</name>
						<name>
							<surname>Caldas</surname>
							<given-names>MA</given-names>
						</name>
						<name>
							<surname>Gebara</surname>
							<given-names>OC</given-names>
						</name>
						<name>
							<surname>Lopes</surname>
							<given-names>NH</given-names>
						</name>
						<name>
							<surname>Ramires</surname>
							<given-names>JA</given-names>
						</name>
					</person-group>
					<article-title>Acute and chronic effects of oestradiol on left ventricular diastolic function in hypertensive postmenopausal women with left ventricular diastolic dysfunction</article-title>
					<source>Heart</source>
					<year>2004</year>
					<volume>90</volume>
					<issue>7</issue>
					<fpage>777</fpage>
					<lpage>781</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1136/hrt.2003.016493">https://doi.org/1010.1136/hrt.2003.016493</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>21 Alecrin IN, Aldrighi JM, Caldas MA, Gebara OC, Lopes NH, Ramires JA. Acute and chronic effects of oestradiol on left ventricular diastolic function in hypertensive postmenopausal women with left ventricular diastolic dysfunction. Heart. 2004;90(7):777-81. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1136/hrt.2003.016493">https://doi.org/1010.1136/hrt.2003.016493</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B22">
				<label>22</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Mohamed</surname>
							<given-names>AL</given-names>
						</name>
						<name>
							<surname>Yong</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Masiyati</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Lim</surname>
							<given-names>L</given-names>
						</name>
						<name>
							<surname>Tee</surname>
							<given-names>SC</given-names>
						</name>
					</person-group>
					<article-title>The prevalence of diastolic dysfunction in patients with hypertension referred for echocardiographic assessment of left ventricular function</article-title>
					<source>Malays J Med Sci</source>
					<year>2004</year>
					<volume>11</volume>
					<issue>1</issue>
					<fpage>66</fpage>
					<lpage>74</lpage>
				</element-citation>
				<mixed-citation>22 Mohamed AL, Yong J, Masiyati J, Lim L, Tee SC. The prevalence of diastolic dysfunction in patients with hypertension referred for echocardiographic assessment of left ventricular function. Malays J Med Sci. 2004;11(1):66-74.</mixed-citation>
			</ref>
			<ref id="B23">
				<label>23</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Liebson</surname>
							<given-names>PR</given-names>
						</name>
						<name>
							<surname>Grandits</surname>
							<given-names>G</given-names>
						</name>
						<name>
							<surname>Prineas</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Dianzumba</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Flack</surname>
							<given-names>JM</given-names>
						</name>
						<name>
							<surname>Cutler</surname>
							<given-names>JA</given-names>
						</name>
						<etal/>
					</person-group>
					<article-title>Echocardiographic correlates of left ventricular structure among 844 mildly hypertensive men and women in the Treatment of Mild Hypertension Study (TOMHS)</article-title>
					<source>Circulation</source>
					<year>1993</year>
					<volume>87</volume>
					<issue>2</issue>
					<fpage>476</fpage>
					<lpage>486</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1161/01.cir.87.2.476">https://doi.org/1010.1161/01.cir.87.2.476</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>23 Liebson PR, Grandits G, Prineas R, Dianzumba S, Flack JM, Cutler JA, et al. Echocardiographic correlates of left ventricular structure among 844 mildly hypertensive men and women in the Treatment of Mild Hypertension Study (TOMHS). Circulation. 1993;87(2):476-86. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1161/01.cir.87.2.476">https://doi.org/1010.1161/01.cir.87.2.476</ext-link>
				</mixed-citation>
			</ref>
			<ref id="B24">
				<label>24</label>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Ferrara</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Gargani</surname>
							<given-names>L</given-names>
						</name>
						<name>
							<surname>Contaldi</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Agoston</surname>
							<given-names>G</given-names>
						</name>
						<name>
							<surname>Argiento</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Armstrong</surname>
							<given-names>WF</given-names>
						</name>
						<etal/>
					</person-group>
					<article-title>RIGHT Heart International NETwork (RIGHT-NET) Investigators. A multicentric quality-control study of exercise Doppler echocardiography of the right heart and the pulmonary circulation. The RIGHT Heart International NETwork (RIGHT-NET)</article-title>
					<source>Cardiovasc Ultrasound</source>
					<year>2021</year>
					<volume>19</volume>
					<issue>1</issue>
					<fpage>9</fpage>
					<lpage>9</lpage>
					<comment>
						<ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1186/s12947-021-00238-1">https://doi.org/1010.1186/s12947-021-00238-1</ext-link>
					</comment>
				</element-citation>
				<mixed-citation>24 Ferrara F, Gargani L, Contaldi C, Agoston G, Argiento P, Armstrong WF, et al.; RIGHT Heart International NETwork (RIGHT-NET) Investigators. A multicentric quality-control study of exercise Doppler echocardiography of the right heart and the pulmonary circulation. The RIGHT Heart International NETwork (RIGHT-NET). Cardiovasc Ultrasound. 2021;19(1):9. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/1010.1186/s12947-021-00238-1">https://doi.org/1010.1186/s12947-021-00238-1</ext-link>
				</mixed-citation>
			</ref>
		</ref-list>
	</back>
	<sub-article article-type="translation" id="S01" xml:lang="pt">
		<front-stub>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Artigo Original</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Tempo de Aceleração na Via de Saída do Ventrículo Direito: Correlação com a Função Diastólica do Ventrículo Esquerdo, Sexo e Idade</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<name>
						<surname>Coimbra</surname>
						<given-names>Renan Macedo</given-names>
					</name>
					<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
					<xref ref-type="corresp" rid="c2"/>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Camarozano</surname>
						<given-names>Ana Cristina</given-names>
					</name>
					<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Sá</surname>
						<given-names>Cintia Rocha Fortes de</given-names>
					</name>
					<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Carmo</surname>
						<given-names>Daniela de Castro</given-names>
					</name>
					<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Fortunato</surname>
						<given-names>Jerônimo Antonio</given-names>
					</name>
					<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Darwich</surname>
						<given-names>Rubens Zenóbio</given-names>
					</name>
					<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Baroncini</surname>
						<given-names>Liz Andréa Villela</given-names>
					</name>
					<xref ref-type="aff" rid="aff2"><sup>1</sup></xref>
				</contrib>
				<aff id="aff2">
					<label>1</label>
					<addr-line>
						<named-content content-type="city">Curitiba</named-content>
						<named-content content-type="state">PR</named-content>
					</addr-line>
					<country country="BR">Brasil</country>
					<institution content-type="original">Hospital da Cruz Vermelha Brasileira, Curitiba, PR, Brasil.</institution>
				</aff>
			</contrib-group>
			<author-notes>
				<corresp id="c2"><bold>Correspondência: Renan Macedo Coimbra •</bold> E-mail: <email>renancoimbra@hotmail.com</email>
				</corresp>
				<fn fn-type="con">
					<p><bold>Contribuição dos autores</bold></p>
					<p>Obtenção de dados: Coimbra RM, Baroncini LAV, Camarozano AC, Carmo DC, Sá CRF, Fortunato JA e Darwich RZ; Análise dos dados: Coimbra RM, Baroncini LAV, Camarozano AC e Carmo DC; Concepção de dados: Coimbra RM, Baroncini LAV e Camarozano AC; Redação do manuscrito: Coimbra RM, Baroncini LAV, Camarozano AC, Carmo DC, Sá CRF, Fortunato JA e Darwich RZ; Revisão crítica do manuscrito quanto ao conteúdo intelectual importante: Coimbra RM, Baroncini LAV, e Camarozano AC.</p>
				</fn>
				<fn fn-type="conflict">
					<p><bold>Conflito de interesses</bold></p>
					<p>Os autores declaram não terem conflitos de interesse.</p>
				</fn>
			</author-notes>
			<abstract>
				<title>Resumo</title>
				<sec>
					<title>Fundamento:</title>
					<p>O tempo de aceleração na artéria pulmonar (TAP) pode ser utilizado para avaliação da hipertensão pulmonar na análise da função diastólica do ventrículo esquerdo.</p>
				</sec>
				<sec>
					<title>Objetivo:</title>
					<p>Avaliar se existe correlação entre o valor do tempo de aceleração na artéria pulmonar e parâmetros da função diastólica do ventrículo esquerdo em indivíduos com função sistólica do ventrículo esquerdo preservada e de acordo com sexo, idade e fatores de risco cardiovasculares.</p>
				</sec>
				<sec>
					<title>Métodos:</title>
					<p>Estudo observacional, transversal. Foram selecionados 119 pacientes (59 mulheres; 49,6%). Os indivíduos foram submetidos ao ecocardiograma transtorácico incluindo os valores de tempo de aceleração na artéria pulmonar; ondas E e A e relação E/A ao Doppler espectral do influxo mitral; ondas e’ septal, e’ lateral e relação E/e’ ao Doppler tecidual do anel mitral; pressão sistólica na artéria pulmonar e volume atrial esquerdo.</p>
				</sec>
				<sec>
					<title>Resultados:</title>
					<p>No sexo feminino, foi encontrada correlação positiva (coeficiente de correlação de Spearman) entre o valor do tempo de aceleração na artéria pulmonar e e’ lateral (coeficiente de correlação de Spearman de 0,47; p=0,002), relação E/A (coeficiente de correlação de Spearman de 0,32; p=0,04) e e’ septal (coeficiente de correlação de Spearman de 0,36; p=0,023) e uma correlação negativa entre o valor do tempo de aceleração na artéria pulmonar e pressão sistólica na artéria pulmonar (coeficiente de correlação de Spearman de -0,43; p=0,034). No sexo masculino, não foi encontrada correlação significativa. Foram encontrados menores valores de tempo de aceleração na artéria pulmonar em mulheres com hipertensão arterial sistêmica quando comparadas a mulheres sem hipertensão arterial sistêmica (0,13±0,03 segundos versus 0,16±0,03 segundos; p = 0,015).</p>
				</sec>
				<sec>
					<title>Conclusão:</title>
					<p>O presente estudo mostrou correlação significativa dos valores do TAP com alguns parâmetros da função diastólica do ventrículo esquerdo apenas no sexo feminino, sendo que mulheres hipertensas apresentaram menores valores de TAP.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="pt">
				<title>Palavras-chave:</title>
				<kwd>Artéria pulmonar</kwd>
				<kwd>Hipertensão pulmonar</kwd>
				<kwd>Ecocardiografia</kwd>
			</kwd-group>
		</front-stub>
		<body>
			<sec sec-type="intro">
				<title>Introdução</title>
				<p>O ecocardiograma transtorácico (ETT) é uma ferramenta nobre na investigação das diversas patologias que acometem o coração, capaz de analisar com precisão não invasiva a interdependência entre as diversas estruturas cardíacas, particularmente a correlação entre a função sistólica dos ventrículos esquerdo (VE) e direito (VD).<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Entretanto, o fluxo que adentra os pulmões e sua correlação com os parâmetros que determinam a função diastólica do VE (FDVE) são pouco investigados.</p>
				<p>O tempo de aceleração na via de saída do VD, também chamado tempo de aceleração na artéria pulmonar (TAP), corresponde ao tempo que leva para o fluxo através da valva pulmonar chegar em seu pico máximo de velocidade estimado por meio do Doppler espectral pulsado na via de saída do VD. Esse valor é tido como normal quando superior a 120 milissegundos e anormal quando abaixo de 105 milissegundos,<sup><xref ref-type="bibr" rid="B2">2</xref> - <xref ref-type="bibr" rid="B4">4</xref></sup> sugerindo a presença de hipertensão pulmonar, mas não sua gravidade. Apesar de não ser tão confiável quanto a velocidade de refluxo tricúspide, que permite estimar de maneira mais precisa a pressão sistólica na artéria pulmonar (PSAP), o TAP é uma ferramenta que também pode ser utilizada nessa avaliação.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
				<p>Avaliar a disfunção diastólica (DD) ventricular esquerda é uma tarefa complexa, que se baseia no uso de diversas medidas e parâmetros ecocardiográficos, entre eles o valor da PSAP. A estimativa desse valor não é possível na ausência de refluxo tricuspídeo adequado.<sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref></sup> Assim, objetivo do presente estudo foi avaliar se existe correlação entre o valor do TAP e os parâmetros da FDVE, em indivíduos com função sistólica de VE preservada, na ausência de DD avançada de VE e de acordo com seco, idade e fatores de risco cardiovasculares.</p>
			</sec>
			<sec sec-type="methods">
				<title>Métodos</title>
				<sec>
					<title>População estudada</title>
					<p>Estudo observacional, transversal. Foram selecionados 119 pacientes, sendo 59 do sexo feminino (49,6%), provenientes do ambulatório de Cardiologia do Hospital da Cruz Vermelha Brasileira de Curitiba (PR), de qualquer etnia, acima de 18 anos, referendados pelo médico assistente para realização de ETT por qualquer indicação clínica.</p>
					<p>A escolha dos pacientes não foi estabelecida por nenhum critério estatístico, mas por conveniência, de acordo com a disponibilidade do indivíduo em participar da pesquisa. Para cada paciente, foi preenchida uma ficha de protocolo envolvendo parâmetros clínicos e ecocardiográficos. Os seguintes dados clínicos foram coletados: idade, sexo, peso, altura, índice de massa corporal (IMC), presença de hipertensão arterial sistêmica (HAS), diabetes melito (DM), doença arterial coronariana (DAC), tabagismo (atual ou pregresso) e dislipidemia. Os diagnósticos de HAS, DM, dislipidemia e tabagismo constavam dos prontuários dos pacientes e/ou foram relatados por eles. A presença de DAC foi confirmada por dados de prontuário médico e do próprio paciente, incluindo infarto do miocárdio não fatal e revascularização miocárdica cirúrgica ou percutânea. Medicamentos em uso regular pelo paciente também foram anotados.</p>
					<p>Os critérios de exclusão foram: pacientes com doenças valvares significativas (moderadas e graves); portadores de próteses valvares; com alterações segmentares de contração do VE por cardiopatia isquêmica ou outras miocardiopatias; com enfisema pulmonar ou doença pulmonar obstrutiva crônica declarada; com hipertensão arterial pulmonar moderada a grave (PSAP &gt;50mmHg); com disfunção contrátil ventricular esquerda (fração de ejeção &lt;52% para homens e &lt;54% para mulheres); portadores de doenças infiltrativas e periocardiopatias; portadores de cardiopatia congênita com hiperfluxo pulmonar com ou sem correção cirúrgica; portadores de marca-passo; com fibrilação atrial e com graus avançados (II e III) de DD de VE .</p>
					<p>Os pacientes foram submetidos a um ETT bidimensional completo obtido de um dos equipamentos de ecocardiografia modelos Philips IE 33, Envisor ou Vivid E General Electric. Todas as janelas acústicas, com todas as medidas e análises ecocardiográficas padrão, foram realizadas em cada paciente. As medidas sonográficas foram feitas por dois ecocardiografistas experientes, com título de habilitação em ecocardiografia pelo Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia (SBC).</p>
					<p>Todos os pacientes assinaram um Termo de Consentimento Livre e Esclarecido em duas vias, sendo que uma ficou em posse do participante da pesquisa. O estudo foi aprovado pelo Comitê de Ética em Pesquisa local.</p>
				</sec>
				<sec>
					<title>Parâmetros ecocardiográficos</title>
					<p>Os parâmetros ecocardiográficos principais analisados neste estudo foram ao Doppler espectral pulsado do influxo mitral, ondas E e A e relação E/A; ao Doppler tecidual pulsado do anel mitral, ondas e’ septal, e’ lateral e relação E/e’ (onda E/média entre e’septal e e’lateral); ao Doppler espectral contínuo do refluxo tricuspídeo, a PSAP em mmHg, por meio da velocidade máxima da regurgitação tricúspide (m/s) quando presente e diâmetro da veia cava inferior (mm);ao Doppler espectral pulsado da via de saída do VD, imediatamente acima dos folhetos da valva pulmonar, o TAP ( <xref ref-type="fig" rid="f5">Figuras 1</xref> e <xref ref-type="fig" rid="f6">2</xref> ), e o volume indexado do átrio esquerdo (normal até 34mL/m² para mulheres e homens), medido usando o método biplanar de Simpson modificado nas projeções ortogonais de quatro câmaras e duas câmaras.</p>
					<fig id="f5">
						<label>Figura 1</label>
						<caption>
							<title>Corte paraesternal transversal ao nível dos vasos da base. Na figura, observa-se o cursor do Doppler pulsado posicionado na via de saída do ventrículo direito, para obtenção do tempo de aceleração na via de saída do ventrículo direito.</title>
						</caption>
						<graphic xlink:href="0102-762X-dic-35-1-eabc242-gf01-pt.tif"/>
					</fig>
					<fig id="f6">
						<label>Figura 2</label>
						<caption>
							<title>Obtenção do tempo de aceleração na via de saída do ventrículo direito ao Doppler pulsado.</title>
						</caption>
						<graphic xlink:href="0102-762X-dic-35-1-eabc242-gf02-pt.tif"/>
					</fig>
					<p>Todas as quantificações e os valores considerados no presente estudo foram baseados nas diretrizes da American Society of Echocardiography e European Society of Cardiovascular Imaging .<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B10">10</xref></sup></p>
				</sec>
				<sec>
					<title>Análise estatística</title>
					<p>A análise estatística foi feita separadamente para os sexos feminino e masculino. Os resultados obtidos no estudo foram descritos por médias, medianas, valores mínimos, valores máximos e desvios-padrões (variáveis quantitativas) ou por frequências e percentuais (variáveis categóricas). Para a avaliação da associação entre duas variáveis quantitativas, foi estimado o coeficiente de correlação de Pearson (CCP) ou de Spearman (CCS). A comparação de dois grupos em relação a variáveis quantitativas foi realizada por meio do teste <italic>t</italic> de Student para amostras independentes ou o teste não paramétrico de Mann-Whitney. Mais de dois grupos foram comparados considerando-se o modelo de análise da variância (Anova) com um fator e o teste <italic>least significant difference</italic> (LSD) para as comparações múltiplas ou o teste não paramétrico de Kruskal-Wallis. A condição de normalidade das variáveis foi avaliada pelo teste de Kolmogorov-Smirnov. Valores de p&lt;0,05 indicaram significância estatística.</p>
					<p>Os dados foram analisados com o programa computacional IBM <italic>Statistical Package for the Social Sciences</italic> (SPSS) Statistics v.20.0. Armonk, NY: IBM Corp.</p>
				</sec>
			</sec>
			<sec sec-type="results">
				<title>Resultados</title>
				<p>A análise final foi feita em 119 indivíduos sendo 60 (50,4%) do sexo masculino (65,1±11,2 anos). As características clínicas da população estudada estão dispostas na <xref ref-type="table" rid="t4">Tabela 1</xref> . <xref ref-type="table" rid="t5"/>
				</p>
				<table-wrap id="t4">
					<label>Tabela 1</label>
					<caption>
						<title>Características básicas da população estudada.</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup width="20%">
							<col/>
							<col/>
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
							<tr>
								<th align="left" valign="middle">Variável</th>
								<th align="center" valign="middle">n</th>
								<th align="center" valign="middle">Sexo feminino</th>
								<th align="center" valign="middle">n</th>
								<th align="center" valign="middle">Sexo masculino</th>
							</tr>
						</thead>
						<tbody style="border-bottom: thin solid; border-color: #000000">
							<tr>
								<td align="left" valign="middle">Idade, anos</td>
								<td align="center" valign="middle">59</td>
								<td align="center" valign="middle">62,6 ± 16,5</td>
								<td align="center" valign="middle">60</td>
								<td align="center" valign="middle">65,1 ± 11,2</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>IMC</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">&lt;30</td>
								<td align="center" valign="middle">41</td>
								<td align="center" valign="middle">72</td>
								<td align="center" valign="middle">41</td>
								<td align="center" valign="middle">68</td>
							</tr>
							<tr>
								<td align="left" valign="middle">≥30</td>
								<td align="center" valign="middle">16</td>
								<td align="center" valign="middle">28</td>
								<td align="center" valign="middle">19</td>
								<td align="center" valign="middle">32</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>HAS</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Sim</td>
								<td align="center" valign="middle">37</td>
								<td align="center" valign="middle">68</td>
								<td align="center" valign="middle">39</td>
								<td align="center" valign="middle">70</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Não</td>
								<td align="center" valign="middle">17</td>
								<td align="center" valign="middle">32</td>
								<td align="center" valign="middle">17</td>
								<td align="center" valign="middle">30</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>Dislipidemia</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Sim</td>
								<td align="center" valign="middle">24</td>
								<td align="center" valign="middle">44</td>
								<td align="center" valign="middle">15</td>
								<td align="center" valign="middle">27</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Não</td>
								<td align="center" valign="middle">30</td>
								<td align="center" valign="middle">56</td>
								<td align="center" valign="middle">41</td>
								<td align="center" valign="middle">73</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>DM</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Sim</td>
								<td align="center" valign="middle">20</td>
								<td align="center" valign="middle">37</td>
								<td align="center" valign="middle">16</td>
								<td align="center" valign="middle">29</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Não</td>
								<td align="center" valign="middle">34</td>
								<td align="center" valign="middle">63</td>
								<td align="center" valign="middle">40</td>
								<td align="center" valign="middle">71</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>DAC</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Sim</td>
								<td align="center" valign="middle">11</td>
								<td align="center" valign="middle">20</td>
								<td align="center" valign="middle">21</td>
								<td align="center" valign="middle">37</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Não</td>
								<td align="center" valign="middle">43</td>
								<td align="center" valign="middle">80</td>
								<td align="center" valign="middle">35</td>
								<td align="center" valign="middle">62</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN4">
							<p>Resultados expressos por média ± desvio-padrão ou %, quando não indicado de outra forma. IMC: índice de massa corporal; HAS: hipertensão arterial sistêmica; DM: diabetes melito; DAC: doença arterial coronariana.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
				<table-wrap id="t5">
					<label>Tabela 5</label>
					<caption>
						<title>Parâmetros Ecocardiográficos basais na população estudada.</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup width="20%">
							<col/>
							<col/>
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
							<tr>
								<th align="left" valign="middle">Variável</th>
								<th align="center" valign="middle">n</th>
								<th align="center" valign="middle">Média</th>
								<th align="center" valign="middle">DP</th>
								<th align="center" valign="middle">Valor de p <xref ref-type="table-fn" rid="TFN5">*</xref>
								</th>
							</tr>
						</thead>
						<tbody style="border-bottom: thin solid; border-color: #000000">
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>Onda E</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">45</td>
								<td align="center" valign="middle">0,75</td>
								<td align="center" valign="middle">0,27</td>
								<td align="center" rowspan="2" valign="middle">0,070</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">43</td>
								<td align="center" valign="middle">0,65</td>
								<td align="center" valign="middle">0,27</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>Onda A</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">41</td>
								<td align="center" valign="middle">0,80</td>
								<td align="center" valign="middle">0,20</td>
								<td align="center" rowspan="2" valign="middle">0,484</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">39</td>
								<td align="center" valign="middle">0,77</td>
								<td align="center" valign="middle">0,24</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>Relação E/A</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">41</td>
								<td align="center" valign="middle">0,97</td>
								<td align="center" valign="middle">0,44</td>
								<td align="center" rowspan="2" valign="middle">0,234</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">39</td>
								<td align="center" valign="middle">0,92</td>
								<td align="center" valign="middle">0,65</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>Onda e’ lateral</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">43</td>
								<td align="center" valign="middle">0,10</td>
								<td align="center" valign="middle">0,04</td>
								<td align="center" rowspan="2" valign="middle">0,835</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">42</td>
								<td align="center" valign="middle">0,09</td>
								<td align="center" valign="middle">0,03</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>Onda e’ septal</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">43</td>
								<td align="center" valign="middle">0,08</td>
								<td align="center" valign="middle">0,03</td>
								<td align="center" rowspan="2" valign="middle">0,509</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">42</td>
								<td align="center" valign="middle">0,07</td>
								<td align="center" valign="middle">0,03</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>Relação E/e’</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">43</td>
								<td align="center" valign="middle">10,0</td>
								<td align="center" valign="middle">4,7</td>
								<td align="center" rowspan="2" valign="middle">0,150</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">41</td>
								<td align="center" valign="middle">8,6</td>
								<td align="center" valign="middle">2,7</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>PSAP</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">31</td>
								<td align="center" valign="middle">28,8</td>
								<td align="center" valign="middle">11,7</td>
								<td align="center" rowspan="2" valign="middle">0,346</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">29</td>
								<td align="center" valign="middle">29,7</td>
								<td align="center" valign="middle">9,0</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>Volume AE</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">35</td>
								<td align="center" valign="middle">36,7</td>
								<td align="center" valign="middle">19,3</td>
								<td align="center" rowspan="2" valign="middle">0,772</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">42</td>
								<td align="center" valign="middle">35,1</td>
								<td align="center" valign="middle">14,0</td>
							</tr>
							<tr>
								<td align="left" colspan="5" valign="middle"><bold>TAC</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">45</td>
								<td align="center" valign="middle">0,15</td>
								<td align="center" valign="middle">0,04</td>
								<td align="center" rowspan="2" valign="middle">0,404</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">37</td>
								<td align="center" valign="middle">0,14</td>
								<td align="center" valign="middle">0,03</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN5">
							<label>*</label>
							<p>Teste t de Student para amostras independentes ou teste não paramétrico de Mann-Whitney, p&lt;0,05. DP: desvio-padrão; PSAP: pressão sistólica de artéria pulmonar; AE: átrio esquerdo; TAC: tempo de aceleração na via de saída do ventrículo direito.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
				<p>No sexo feminino, foi encontrada correlação positiva e significativa entre o valor do TAP com o e’ lateral (CCS de 0,47; p=0,002), com a relação E/A (CCS de 0,32; p=0,04) e com o e’ septal (CCS de 0,36; p=0,023) e uma correlação negativa entre o valor do TAP e a PSAP (CCS de -0,43; p=0,034) ( <xref ref-type="fig" rid="f7">Figuras 3</xref> e <xref ref-type="fig" rid="f8">4</xref> ). As demais variáveis não se correlacionaram com o TAP, sendo que, no sexo masculino, nenhuma correlação significativa foi encontrada entre os parâmetros analisados ( <xref ref-type="table" rid="t6">Tabela 3</xref> ).</p>
				<fig id="f7">
					<label>Figura 3</label>
					<caption>
						<title>Correlação entre tempo de aceleração na pulmonar e ondas E’ lateral e E’ medial no sexo feminino.</title>
					</caption>
					<graphic xlink:href="0102-762X-dic-35-1-eabc242-gf03-pt.tif"/>
				</fig>
				<fig id="f8">
					<label>Figura 4</label>
					<caption>
						<title>Correlação entre tempo de aceleração na pulmonar e relação E/A e pressão sistólica na artéria pulmonar.</title>
					</caption>
					<graphic xlink:href="0102-762X-dic-35-1-eabc242-gf04-pt.tif"/>
				</fig>
				<table-wrap id="t6">
					<label>Tabela 3</label>
					<caption>
						<title>Correlação entre valores de tempo de aceleração na via de saída do ventrículo direito e parâmetros da função diastólica.</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup width="25%">
							<col/>
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
							<tr>
								<th align="center" valign="middle">Sexo</th>
								<th align="center" valign="middle">n</th>
								<th align="center" valign="middle">r</th>
								<th align="center" valign="middle">Valor de p</th>
							</tr>
						</thead>
						<tbody style="border-bottom: thin solid; border-color: #000000">
							<tr>
								<td align="left" colspan="4" valign="middle"><bold>TAP X relação E/A</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">41</td>
								<td align="center" valign="middle">0,32</td>
								<td align="center" valign="middle">0,040</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">35</td>
								<td align="center" valign="middle">0,32</td>
								<td align="center" valign="middle">0,061</td>
							</tr>
							<tr>
								<td align="left" colspan="4" valign="middle"><bold>TAP X onda e’ septal</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">40</td>
								<td align="center" valign="middle">0,36</td>
								<td align="center" valign="middle">0,023</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">35</td>
								<td align="center" valign="middle">0,30</td>
								<td align="center" valign="middle">0,081</td>
							</tr>
							<tr>
								<td align="left" colspan="4" valign="middle"><bold>TAP X relação E/e’</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">40</td>
								<td align="center" valign="middle">-0,13</td>
								<td align="center" valign="middle">0,436</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">35</td>
								<td align="center" valign="middle">-0,04</td>
								<td align="center" valign="middle">0,822</td>
							</tr>
							<tr>
								<td align="left" colspan="4" valign="middle"><bold>TAP X PSAP</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">25</td>
								<td align="center" valign="middle">-0,43</td>
								<td align="center" valign="middle">0,034</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">19</td>
								<td align="center" valign="middle">-0,21</td>
								<td align="center" valign="middle">0,380</td>
							</tr>
							<tr>
								<td align="left" colspan="4" valign="middle"><bold>TAP X VAE</bold></td>
							</tr>
							<tr>
								<td align="left" valign="middle">Feminino</td>
								<td align="center" valign="middle">28</td>
								<td align="center" valign="middle">-0,08</td>
								<td align="center" valign="middle">0,701</td>
							</tr>
							<tr>
								<td align="left" valign="middle">Masculino</td>
								<td align="center" valign="middle">29</td>
								<td align="center" valign="middle">-0,11</td>
								<td align="center" valign="middle">0,577</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN6">
							<p>TAP: tempo de aceleração na pulmonar; PSAP: pressão sistólica na artéria pulmonar; VAE: volume do átrio esquerdo.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
				<p>O valor do TAP não foi influenciado por sexo, IMC, DM, dislipidemia, DAC e tabagismo (dados não mostrados). Entretanto, foram encontrados menores valores de TAP em mulheres com HAS quando comparadas a mulheres sem HAS (0,13±0,03 segundos <italic>versus</italic> 0,16±0,03 segundos; p = 0,015).</p>
				<p>A idade não apresentou correlação significativa com o TAP em ambos os sexos (CCS de -0,27; p 0,068 para o sexo feminino e CCS de -0,31; p 0,065 para o masculino).</p>
			</sec>
			<sec sec-type="discussion">
				<title>Discussão</title>
				<p>O presente estudo encontrou correlação significativa positiva entre o TAP e parâmetros da FDVE (ondas e’ septal e lateral e relação E/A) apenas no sexo feminino, sendo que, também entre as mulheres, a presença de HAS se associou a menores valores de TAP. Entretanto, na análise geral da população aqui estudada, não foram encontradas diferenças significativas nos valores do TAP entre os sexos ou de acordo com idade e IMC.</p>
				<p>Atualmente, o dado relacionado à hipertensão pulmonar (HP) mais utilizado na avaliação da FDVE é a PSAP. Habitualmente, utiliza-se a PSAP estimada pelo refluxo valvar tricúspide para se avaliar o grau de HP. Sabe-se que o TAP apresenta correlação negativa em relação à PSAP (dado também encontrado no presente estudo). Conforme Granstam et al.,<sup><xref ref-type="bibr" rid="B11">11</xref></sup> durante o exame de ETT, a regurgitação tricúspide pode não estar presente ou não ser confiável para a correta estimativa da PSAP. Levando esse fato em consideração, em seu estudo, a resistência vascular pulmonar, estimada de forma invasiva, foi correlacionada a valores de TAP como possível alternativa para estimar a presença de HP. Assim, levando em consideração os achados de Granstam et al., é interessante haver mais de um método que possibilite a estimativa da HP durante o estudo da FDVE, principalmente nos casos em que não é possível se estimar o refluxo tricúspide, ou o mesmo não seja confiável, e nos casos iniciais de DD, em que não existe ainda um aumento significativo da pressão pulmonar. Na presença de uma função sistólica de VE preservada, a diferenciação entre função diastólica normal e anormal se torna complicada, devido à sobreposição de valores nos índices obtidos ao Doppler. Embora seja de conhecimento que a idade altera estruturalmente tanto o coração quanto os vasos, ao se compararem indivíduos mais idosos saudáveis, os valores obtidos ao Doppler são semelhantes aos encontrados em faixa etárias mais jovens (entre 40 e 60 anos de idade).<sup><xref ref-type="bibr" rid="B12">12</xref></sup> Considerando a média de idade da população aqui estudada (indivíduos relativamente jovens), sendo todos com função sistólica de VE preservada, não eram esperadas diferenças significativas nos parâmetros avaliados ao Doppler. Entretanto, era esperado que a inclusão dos valores do TAP pudesse diferenciar estágios inicias de DD, em que a PSAP ainda não está muito elevada.</p>
				<p>No estudo realizado por Baroncini et al.,<sup><xref ref-type="bibr" rid="B13">13</xref></sup> com 87 indivíduos, houve também correlação negativa entre os valores de TAP e a idade e correlação positiva entre TAP e relação E/A, sem significância entre outras variáveis e sexo. Esse estudo demonstrou que valores de TAP menores que 0,135 segundo foram associados à DD grau I e valores maiores que 0,135 segundo foram associados à diástole normal. Pode-se concluir, por esses estudos, que os valores de TAP se correlacionam com os parâmetros que avaliam a FDVE, mesmo nos estados precoces, quando ainda não existem sinais de hipertensão arterial pulmonar significativa. Nesse estágio, a relação E/e’ ainda é baixa, assim como os valores do TAP ainda se encontram dentro da normalidade (acima de 120 milissegundos).<sup><xref ref-type="bibr" rid="B14">14</xref> , <xref ref-type="bibr" rid="B15">15</xref></sup></p>
				<p>Em estudo com número maior de participantes, Marra et al.,<sup><xref ref-type="bibr" rid="B16">16</xref></sup> analisando 1.029 indivíduos saudáveis, também não encontraram valores diferentes de TAP entre homens e mulheres, mas perceberam pequena redução desse parâmetro com o avanço da idade, o aumento do IMC e maiores valores de pressão arterial sistêmica sistólica e diastólica. Também semelhante aos achados aqui apresentados, encontraram correlação positiva entre o TAP e a relação E/A, sem, contudo, discutirem esse último achado, sugerindo mais estudos nesta área.</p>
				<p>Em um estudo realizado por Zabalgoitia et al.,<sup><xref ref-type="bibr" rid="B17">17</xref></sup> foram examinados, de maneira prospectiva, 508 pacientes hipertensos em relação à massa do VE, à espessura relativa da parede e à interação sistólica e diastólica em indivíduos entre 50 e 80 anos, de acordo com idade e sexo. Nos homens, a maioria das medidas foi distribuída de maneira semelhante. No entanto, mulheres com 65 anos ou mais de idade tiveram menores dimensões sistólicas do VE, espessuras ventriculares maiores, maior encurtamento porcentual e menor estresse sistólico final da parede, ou seja, as alterações estruturais e funcionais foram mais pronunciadas no sexo feminino.</p>
				<p>Os achados que, no presente estudo, demonstraram significância estatística particularmente para o sexo feminino, se correlacionados aos achados do estudo de Zalbalgoitia et al.,17 indicam a importância de aprofundar as pesquisas relacionadas à função ventricular sistólica, função diastólica, possível influência hormonal e comportamento da HAS no coração feminino. Prévios estudos já relataram a influência hormonal em mulheres pré e pós-menopausa e a maior incidência de insuficiência cardíaca com fração de ejeção preservada (ICFEP) em mulheres quando comparadas a indivíduos do sexo masculino.<sup><xref ref-type="bibr" rid="B18">18</xref> , <xref ref-type="bibr" rid="B19">19</xref></sup> Da mesma maneira, a presença de HAS provoca alterações estruturais diferentes nos padrões geométricos dos ventrículos em homens e mulheres, com possíveis efeitos deletérios mais acentuados no sexo feminino.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
				<p>Em um estudo realizado por Alecrin et al.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> com mulheres hipertensas na pós-menopausa, a terapia de reposição hormonal com estradiol por via oral por um período de 12 semanas demonstrou melhora significativa na FDVE ao ETT. Mohamed et al.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> correlacionaram a DD com a idade e a hipertensão arterial e concluíram que a duração da hipertensão arterial, os níveis de hipertensão arterial sistólica e diastólica e a idade dos pacientes são indicadores prognósticos importantes na previsão do desenvolvimento de DD em pacientes hipertensos. A melhor compreensão dessas particularidades pode propiciar avanços futuros em questões relacionadas a tratamentos anti-hipertensivos e da insuficiência cardíaca congestiva.</p>
				<p>Liebson et al.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> avaliaram uma grande população de homens (511) e mulheres (333) com hipertensão primária leve e, dentre eles, houve porcentagem substancial de participantes com hipertrofia do VE determinada ecocardiograficamente. Nesse estudo, os índices de massa do VE correlacionaram-se positivamente com pressão arterial sistólica, IMC, excreção urinária de sódio e tabagismo, sem diferença significativa entre os sexos masculino e feminino. Diferentemente do presente estudo, não foram avaliadas as variáveis relacionadas à função diastólica, porém, com um número de participantes maior, como no referido estudo, seria possível obter também mais variáveis relacionadas aos mesmos fatores de risco cardiovasculares abordados.</p>
				<p>A principal limitação do presente estudo é o número pequeno de participantes (119), principalmente quando comparado a outros achados de literatura. Esse fato facilita o aparecimento de casos isolados ( <italic>outliers</italic> ) que podem influenciar nos resultados aqui apresentados. Outro fator relevante foi a exclusão de pacientes com graus mais avançados de DD, não possibilitando avaliar o comportamento dos valores de TAP nessas situações. Entretanto, o objetivo principal foi justamente avaliar o comportamento do TAP nos estágios iniciais de DD ventricular esquerda. Sabe-se, também, que pode existir variabilidade intra e interobservador com relação à obtenção das várias medidas ecocardiográficas,<sup><xref ref-type="bibr" rid="B24">24</xref></sup> mas essa análise não foi realizada nos parâmetros aqui avaliados. Entretanto, nenhum dos trabalhos aqui citados na discussão com relação ao TAP apresentaram tal análise. Da mesma maneira, a aferição da frequência cardíaca e a medida da pressão arterial também não foram feitas concomitantemente aos estudos realizados. De acordo com o trabalho de Marra et al.,<sup><xref ref-type="bibr" rid="B16">16</xref></sup> que analisou oito estudos prévios em 1.029 indivíduos saudáveis, os valores de TAP foram influenciados fracamente tanto pela FC quanto pela pressão arterial.</p>
			</sec>
			<sec sec-type="conclusions">
				<title>Conclusão</title>
				<p>O presente estudo correlacionou valores de tempo de aceleração na via de saída do ventrículo direito com sinais de disfunção diastólica inicial do ventrículo esquerdo apenas no sexo feminino. Entre os fatores de risco cardiovasculares, a presença de hipertensão arterial sistêmica influenciou nos valores do tempo de aceleração na via de saída do ventrículo direito apenas no sexo feminino.</p>
			</sec>
		</body>
	</sub-article>
</article>