<?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="review-article" dtd-version="1.1" specific-use="sps-1.9" xml:lang="en" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">
	<front>
		<journal-meta>
			<journal-id journal-id-type="publisher-id">abcimg</journal-id>
			<journal-title-group>
				<journal-title>ABC Imagem Cardiovascular</journal-title>
				<abbrev-journal-title abbrev-type="publisher">Arq Bras Cardiol: Imagem cardiovasc</abbrev-journal-title>
			</journal-title-group>
			<issn pub-type="epub">2675-312X</issn>
			<publisher>
				<publisher-name>Sociedade Brasileira de Cardiologia</publisher-name>
			</publisher>
		</journal-meta>
		<article-meta>
			<article-id pub-id-type="publisher-id">abcimg.20240043i</article-id>
			<article-id pub-id-type="doi">10.36660/abcimg.20240043i</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Review Article</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Echocardiographic Assessment of Left Atrial Function in Aging Adults</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<name>
						<surname>Oliveira</surname>
						<given-names>Fernando Rodrigues da Camara</given-names>
					</name>
					<role>Conception and design of the research and critical revision of the manuscript for intellectual content</role>
					<role>Acquisition of data</role>
					<role>analysis and interpretation of the data and writing of the manuscript</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0002-8891-057X</contrib-id>
					<name>
						<surname>Resende</surname>
						<given-names>Marcos Valerio Coimbra de</given-names>
					</name>
					<role>Conception and design of the research and critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Vieira</surname>
						<given-names>Marcelo Luiz Campos</given-names>
					</name>
					<role>Conception and design of the research and critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
					<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff1">
				<label>1</label>
				<institution content-type="orgdiv2">Instituto do Câncer do Estado de São Paulo</institution>
				<institution content-type="orgdiv1">Hospital das Clínicas da Faculdade de Medicina</institution>
				<institution content-type="orgname">Universidade de São Paulo</institution>
				<addr-line>
					<named-content content-type="city">São Paulo</named-content>
					<named-content content-type="state">SP</named-content>
				</addr-line>
				<country country="BR">Brasil</country>
				<institution content-type="original">Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brasil</institution>
			</aff>
			<aff id="aff2">
				<label>2</label>
				<institution content-type="orgname">Hospital Israelita Albert Einstein</institution>
				<addr-line>
					<named-content content-type="city">São Paulo</named-content>
					<named-content content-type="state">SP</named-content>
				</addr-line>
				<country country="BR">Brasil</country>
				<institution content-type="original">Hospital Israelita Albert Einstein, São Paulo, SP – Brasil</institution>
			</aff>
			<aff id="aff3">
				<label>3</label>
				<institution content-type="orgname">Universidade de São Paulo</institution>
				<institution content-type="orgdiv1">Instituto do Coração</institution>
				<addr-line>
					<named-content content-type="city">São Paulo</named-content>
					<named-content content-type="state">SP</named-content>
				</addr-line>
				<country country="BR">Brasil</country>
				<institution content-type="original">Universidade de São Paulo, Instituto do Coração, São Paulo, SP – Brasil</institution>
			</aff>
			<author-notes>
				<corresp id="c01"> Mailing Address: Fernando Rodrigues da Camara Oliveira • Hospital Israelita Albert Einstein. Avenida Albert Einstein, 627. Postal Code: 05652-900. São Paulo, SP – Brasil E-mail: <email>fernandocamaracardio@gmail.com</email>
				</corresp>
				<fn fn-type="conflict">
					<p>Potential Conflict of Interest</p>
					<p>No potential conflict of interest relevant to this article was reported.</p>
				</fn>
				<fn fn-type="edited-by">
					<p>Editor responsible for the review: Marcelo Dantas</p>
				</fn>
			</author-notes>
			<pub-date date-type="pub" publication-format="electronic">
				<day>02</day>
				<month>08</month>
				<year>2024</year>
			</pub-date>
			<pub-date date-type="collection" publication-format="electronic">
				<month>07</month>
				<year>2024</year>
			</pub-date>
			<volume>37</volume>
			<issue>3</issue>
			<elocation-id>e20240043</elocation-id>
			<history>
				<date date-type="received">
					<day>28</day>
					<month>05</month>
					<year>2024</year>
				</date>
				<date date-type="rev-recd">
					<day>29</day>
					<month>05</month>
					<year>2024</year>
				</date>
				<date date-type="accepted">
					<day>1</day>
					<month>06</month>
					<year>2024</year>
				</date>
			</history>
			<permissions>
				<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
					<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
				</license>
			</permissions>
			
			<abstract>
				<title>Abstract</title>
				<p>Cardiovascular diseases (CVD) are the main cause of death in Brazil, with aging being a major risk factor. Research indicates that there is a higher occurrence of cardiovascular disease as individuals age, impacting ventricular hypertrophy, diastolic dysfunction, and atrial fibrillation. Atrial myopathy, associated with aging, has received considerable attention, with oxidative stress and chronic inflammation under investigation as contributing factors. Left atrial function has been extensively studied, focusing on its role in cardiac performance. Modern echocardiographic techniques, such as speckle tracking, provide a detailed assessment of atrial function, offering advantages over traditional methods of assessing maximum atrial volume. Studies reveal the important role of atrial strain in predicting cardiovascular events. The aging process brings a progressive reduction in atrial functions, and new measures are being developed to detect atrial dysfunction early, with a potential impact on future guidelines and the definition of normal age-related standards.</p>
			</abstract>
			<kwd-group xml:lang="en">
				<kwd>Atrial cardiomyopathy</kwd>
				<kwd>left atrial strain</kwd>
				<kwd>speckle tracking echocardiography</kwd>
				<kwd>aging</kwd>
			</kwd-group>
			<counts>
				<fig-count count="2"/>
				<table-count count="0"/>
				<equation-count count="0"/>
				<ref-count count="22"/>
			</counts>
		</article-meta>
	</front>
	<body>
		
				<p>
					<fig id="f01">
						<label>Central Illustration</label>
						<caption>
							<title>: Echocardiographic Assessment of Left Atrial Function in Aging Adults</title>
							<p>Exemplo de análise do strain atrial esquerdo nos cortes apicais de 4 e 2 câmaras com o software Echopac® (GE), utilizando o complexo QRS como referência para aferição. S_CD: strain de conduto; S_CT: strain de contração atrial; S_R: strain de reservatório. Notam-se os valores por corte e o valor médio considerando todos os seguimentos atriais.</p>
						</caption>
						<graphic xlink:href="2675-312X-abcimg-37-03-e20240043-gf01.tif"/>
					</fig>
				</p>
			
		<sec sec-type="intro">
			<title>Introduction</title>
			<p>Cardiovascular diseases (CVD) are the main cause of death in Brazil, and the aging process is among the main risk factors for CVD. CVD prevalence increases with age, regardless of gender.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> A study published in 2019<sup><xref ref-type="bibr" rid="B2">2</xref></sup> showed that the chance of an individual aged 65 or over having CVD is 4.7 times greater in Brazil. Data derived from the BLSA study (The Framingham Heart Study and the Baltimore Longitudinal Study on Aging)<sup><xref ref-type="bibr" rid="B3">3</xref></sup> revealed that aging individuals without concomitant CVD experience increased ventricular hypertrophy, diastolic dysfunction, declined physical fitness and increased prevalence of atrial fibrillation.</p>
			<p>There has been a growing focus on the role of left atrial function in cardiovascular morbidity, with atrial myopathy recognized as an independent condition primarily linked to the aging process.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Animal models have demonstrated that aging is related to structural changes and modifications in atrial electrophysiological properties.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Oxidative stress, calcium dysregulation, and chronic inflammation leading to the final pathway of fibrosis<sup><xref ref-type="bibr" rid="B6">6</xref></sup> have been investigated as important agents of this process. The diseased atrium brings together conditions that predispose to blood stasis and endothelial dysfunction, favoring embolic phenomena.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
			<p>Besides recognizing atrial myopathy as the underlying cause of the well-established link between atrial fibrillation and cardioembolic events, there has been significant progress in understanding the impairment of atrial function itself, advancing to the extent that there is now recognition of atrial insufficiency as a distinct clinical entity. Atrial insufficiency is defined as any dysfunction of the atria – be it anatomical, mechanical, electrical, and/or rheological – leading to compromised cardiac function and associated symptoms.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> The left atrium (LA) plays a fundamental role in ventricular filling. The physiology of the left atrium can be investigated and better determined through the analysis of the different phases of its contribution to ventricular filling, namely reservoir, conduit, and atrial contraction phases. The capacity of the atrial reservoir when filling during ventricular systole from the pulmonary veins corresponds to 40 to 50% of the systolic volume. Passive transfer during ventricular diastole (conduit function), by 20 to 30%. Active contraction of the atrium then transfers the remaining volume. Reduction in atrial function in any of these phases can lead to impaired overall cardiac performance and worse outcomes.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
			<sec>
				<title>Echocardiographic Analysis of Left Atrial Function</title>
				<p>Biplanar measurement of maximum indexed left atrial volume (LAViMax) is widely utilized and recommended by guidelines for assessing atrial structure. This parameter is typically straightforward to obtain and has been extensively studied for its correlation with outcomes in patients with both preserved and reduced ejection fractions. The maximum atrial volume reflects the cumulative impact of processes contributing to atrial myopathy over time. Observational studies with more than 6 thousand patients have demonstrated that a maximum index volume of 34 ml/m<sup>2</sup> is an independent predictor of death, heart failure (HF), atrial fibrillation and ischemic stroke.<sup><xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup> However, the development of new cardiovascular imaging techniques has allowed for a more detailed analysis of not only the structure but also the functional characteristics of the left atrium.</p>
				<p>The advent of speckle tracking technology has enabled faster and more reproducible analysis of atrial myocardial deformation throughout the cardiac cycle, mainly due to its independence in relation to the insonation. It is currently possible to quantify, through dedicated software, atrial peak or reservoir function (PALS or LAS-r), conduit (LAS-cd), and atrial contraction (LAS-ct)<sup><xref ref-type="bibr" rid="B10">10</xref></sup> based on semi-automated analysis of apical images in two and four chambers focused on the left atrium (<xref ref-type="fig" rid="f01">Central Illustration</xref>). Research has shown that evaluating atrial function, particularly reservoir function, offers significant advantages over summarizing maximum atrial volume alone, as functional changes often manifest before structural changes become apparent.<sup><xref ref-type="bibr" rid="B11">11</xref></sup></p>
				<p>Studies have demonstrated a noteworthy correlation between reduced LAS-r and the presence of atrial fibrosis, as assessed through magnetic resonance imaging and pathological studies.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> An interesting study<sup><xref ref-type="bibr" rid="B12">12</xref></sup> analyzed the pre-operative atrial strain of 46 patients with mitral prolapse referred for cardiac surgery and who had histological atrial samples collected. LAS-r showed an important correlation with the degree of fibrosis in the anatomopathological study (r = -0.82, p &lt; 0.0001). In contrast, atrial volume, atrial ejection fraction and Doppler-derived parameters (E/e’ ratio) showed a weak correlation.</p>
				<p>The analysis of atrial mechanics also reflects the important atrioventricular interaction, considering that mid-systole atrial distension is influenced by the mitral annulus movement, in addition to ventricular compliance also interfering with the atrial emptying process (passive and active).<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Therefore, atrial strain is also an important parameter for ventricular function assessment. A study with 80 patients<sup><xref ref-type="bibr" rid="B14">14</xref></sup> referred for cardiac catheterization demonstrated that, among patients with an ejection fraction ≤ 30%, a LAS-r value &lt; 18% was more accurate than the E/e’ ratio in predicting a left ventricular end-diastolic pressure greater than 12 mmHg.</p>
				<p>The close relationship between atrial and ventricular mechanics is also evidenced by the additional value of atrial strain analysis in the diagnosis of diastolic dysfunction, which may contribute to reducing the frequent diagnosis of “indeterminate diastolic function” according to current guidelines from the American Society of Echocardiography (ASE).<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Among 517 patients considered at risk of developing diastolic dysfunction (with high blood pressure, diabetes, or history of coronary disease),<sup><xref ref-type="bibr" rid="B15">15</xref></sup> the reduction in LAS-r was more common than the increase in LAVI (36.9% vs. 15.5%; p &lt; 0.01), and 29.4% of patients with normal LAViMax had reduced LAS-r. In this population, adding the LAS-r value &lt; 23% as an additional diagnostic parameter for diastolic dysfunction alongside those determined by ASE, has increased the detection of diastolic dysfunction from 13.5% to 23.4% (p &lt; 0.01). Furthermore, LAS-r &lt; 23% was associated with the worst NYHA (New York Heart Association) functional class, even when LAViMax was normal.</p>
				<p>Given the capacity for early detection of atrial and ventricular functional changes, the prognostic value of atrial strain has been demonstrated in several clinical contexts. A prospective study with 312 patients<sup><xref ref-type="bibr" rid="B16">16</xref></sup> demonstrated that LAS-r had the best capacity (area under the curve: 0.83) to predict in 3,1 ± 1,4 years the occurrence of atrial fibrillation, HF, stroke, transient ischemic attack, myocardial infarction, coronary revascularization, and cardiovascular death, in relation to LAVI (area under the curve: 0,71).</p>
				<p>Atrial strain analysis also allows for a non-invasive assessment of the atrial stiffness index (LASI), defined as the relationship between mean E/e’ and LAS-r. High atrial stiffness results from chronic exposure of the left atrium to high filling pressures. It represents a reduction in atrial compliance, with volumetric variations resulting in a large increase in atrial pressures. One study retrospectively evaluated 307 patients<sup><xref ref-type="bibr" rid="B17">17</xref></sup> with increased invasive measurement of final ventricular filling pressure (≥ 16 mmHg) and who underwent an echocardiogram within an interval of up to 7 days. In this population, a LASI &gt; 0.26 showed better performance (area under the curve: 0.743; 95% CI: 0.681-0.806) to predict death from any cause or hospitalization due to HF in relation to the classic parameters for analyzing diastolic function (mean E/e’, tricuspid regurgitation velocity, and LAViMax).</p>
				<p>Volumetric data also continues to be explored. By employing three-dimensional echocardiography or atrial strain curves, it becomes feasible to accurately quantify the variation in left atrial volume throughout the entire cardiac cycle, rather than solely measuring the maximum volume at the end of systole, which is conventional. In an elderly population (71 ± 9 years), research has demonstrated that the minimum volume at the end of diastole, rather than the maximum volume, shows a stronger association with cardiovascular events, maybe because it represents the phase of the cardiac cycle when the atrium is most affected by ventricular filling pressures.<sup><xref ref-type="bibr" rid="B18">18</xref></sup></p>
			</sec>
			<sec>
				<title>Left Atrial Function and the Aging Process</title>
				<p>Recent studies have aimed to establish normal values for atrial strain, considering its age-related variability. It is well-known that as individuals age, there is a gradual reversal in the relationship between rapid ventricular filling and atrial contraction. Starting from the fifth decade of life, there is a slowing of ventricular relaxation, leading to impaired early ventricular filling and a compensatory increase in late filling.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Interestingly, findings from the NORRE study (Normal Reference Ranges for Echocardiography)<sup><xref ref-type="bibr" rid="B20">20</xref></sup> have shown a progressive decline in reservoir (LAS-r) and conduit (LAS-cd) functions with age, accompanied by an increase in pump function (LAS-ct) and the atrial stiffness index. The minimum expected values for LAS -r were 31.1% for individuals aged 20 to 40 years, 27.7% for those aged 40 to 60 years, and 22.7% for those aged 60 and older. In contrast, the minimum values for LAS-ct were 7.2%, 9.3%, and 7.7%, respectively.</p>
				<p>A more recent study<sup><xref ref-type="bibr" rid="B21">21</xref></sup> based on HUNT4Echo (The Echocardiographic substudy of the 4th wave of the Trøndelag Health Study), including 1329 patients, also sought to determine normal values for atrial strain. Unlike the NORRE study, which used the VIS software (Tomtec), the HUNT4Echo data were analyzed by Echopac (GE). The results also reveal a negative association between age and reservoir and conduit strains.</p>
				<p>Finally, a study published in the Journal of the American College of Cardiology in April 2022 specifically explored the behavior of atrial structure and function in elderly patients.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> In the article by Inciardi et al., the LAViMAx measurement is initially emphasized as the most commonly used measure to measure the LA, being recommended by the main international cardiology societies. However, they emphasize the potential of incorporating new measurements and functional analyses using advanced techniques to provide additional insights for the early detection of atrial dysfunction, potentially identifying issues before structural changes become evident.</p>
				<p>This is the analysis of a multicenter cohort of patients from the ARIC study (Atherosclerosis Risk in Communities Study), using new LA assessment measures in a population of 4901 participants over 65 years of age, presenting sinus rhythm and without HF. The objectives of the study were to evaluate variations in LA structural and functional measurements and their correlation with NT-proBNP and incidence of the combined outcome of death or HF in an average prospective follow-up of 5.5 years.</p>
				<p>In addition to the conventional structural measurement of LAViMax, two other measurements were performed: the minimum LA volume (LAViMin) and the LA emptying fraction (LAEF). Functional measurements of the LA reservoir, conduit and contractile derived from two-dimensional strain were also performed. Interestingly, an initial cohort of 301 patients without pre-existing CVD was studied to establish the normal limits of the assessed parameters, defined as values between the 10th and 90th percentiles.</p>
				<p>After a mean follow-up time of 5.5 years and adjustments for clinical confounding factors, ventricular function, and NT-proBNP, with the exception of LAViMax, all other structural and functional parameters under investigation (including LAViMin) remained significantly associated with a greater incidence of the combined outcome. The variables were identified as predictors of unfavorable outcomes, even when excluding patients with increased LAViMax or analyzing the outcomes separately between the groups of patients who developed HF with reduced or preserved ejection fraction.</p>
				<p>Reservoir and conduit atrial strains showed a non-linear relationship between outcomes, with a significant increase in the combined incidence of death and HF with values below 28% and 11%, respectively. Thus, the conventional measurement of left atrial dimension was found to be less reliable in this elderly population compared to the measurement of minimum indexed atrial volume and functional parameters derived from atrial strain. It is important to note that the upper normal values (90th percentile) identified in this group for LAViMax were 37.8 ml/m<sup>2</sup> for women and 42.7 ml/m<sup>2</sup> for men, indicating that current guidelines may underestimate normal values for older people.</p>
			</sec>
		</sec>
		<sec sec-type="conclusions">
			<title>Conclusion</title>
			<p>The development of new echocardiographic techniques has allowed a more detailed analysis of left atrial function. The integration of functional data with structural analysis enabled the characterization of left atrial function throughout the entire cardiac cycle, in addition to establishing its relationship with left ventricular function and determining the changes resulting from pathological processes and aging. Previously viewed primarily as a “buffer chamber” affected by ventricular dysfunction, the assessment of dynamic parameters has revealed the early onset of atrial dysfunction, actively contributing to reduced overall cardiac performance and holding prognostic significance across various contexts. Advancements in technology and the adoption of more automated methods, including artificial intelligence, are expanding the accessibility of functional analysis of the left atrium. Future studies should integrate these insights into guidelines to enhance understanding of the anticipated variations in normal values due to aging.</p>
		</sec>
	</body>
	<back>
		<ref-list>
			<title>References</title>
			<ref id="B1">
				<label>1</label>
				<mixed-citation>1. Oliveira GMM, Brant LCC, Polanczyk CA, Malta DC, Biolo A, Nascimento BR, et al. Estatística Cardiovascular - Brasil 2023. Arq Bras Cardiol. 2024;121(2):e20240079. doi: 10.36660/abc.20240079.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Oliveira</surname>
							<given-names>GMM</given-names>
						</name>
						<name>
							<surname>Brant</surname>
							<given-names>LCC</given-names>
						</name>
						<name>
							<surname>Polanczyk</surname>
							<given-names>CA</given-names>
						</name>
						<name>
							<surname>Malta</surname>
							<given-names>DC</given-names>
						</name>
						<name>
							<surname>Biolo</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Nascimento</surname>
							<given-names>BR</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Estatística Cardiovascular - Brasil 2023</article-title>
					<source>Arq Bras Cardiol</source>
					<year>2024</year>
					<volume>121</volume>
					<issue>2</issue>
					<elocation-id>e20240079</elocation-id>
					<pub-id pub-id-type="doi">10.36660/abc.20240079</pub-id>
				</element-citation>
			</ref>
			<ref id="B2">
				<label>2</label>
				<mixed-citation>2. Gonçalves RPF, Haikal DS, Freitas MIF, Machado ÍE, Malta DC. Self-Reported Medical Diagnosis of Heart Disease and Associated Risk Factors: National Health Survey. Rev Bras Epidemiol. 2019;22(Suppl 2):E190016.SUPL.2. doi: 10.1590/1980-549720190016.supl.2.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Gonçalves</surname>
							<given-names>RPF</given-names>
						</name>
						<name>
							<surname>Haikal</surname>
							<given-names>DS</given-names>
						</name>
						<name>
							<surname>Freitas</surname>
							<given-names>MIF</given-names>
						</name>
						<name>
							<surname>Machado</surname>
							<given-names>ÍE</given-names>
						</name>
						<name>
							<surname>Malta</surname>
							<given-names>DC</given-names>
						</name>
					</person-group>
					<article-title>Self-Reported Medical Diagnosis of Heart Disease and Associated Risk Factors: National Health Survey</article-title>
					<source>Rev Bras Epidemiol</source>
					<year>2019</year>
					<volume>22</volume>
					<supplement>Suppl 2</supplement>
					<elocation-id>E190016.SUPL.2</elocation-id>
					<pub-id pub-id-type="doi">10.1590/1980-549720190016.supl.2</pub-id>
				</element-citation>
			</ref>
			<ref id="B3">
				<label>3</label>
				<mixed-citation>3. Lakatta EG, Levy D. Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part II: The Aging Heart in Health: Links to Heart Disease. Circulation. 2003;107(2):346-54. doi: 10.1161/01.cir.0000048893.62841.f7.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lakatta</surname>
							<given-names>EG</given-names>
						</name>
						<name>
							<surname>Levy</surname>
							<given-names>D</given-names>
						</name>
					</person-group>
					<article-title>Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part II: The Aging Heart in Health: Links to Heart Disease</article-title>
					<source>Circulation</source>
					<year>2003</year>
					<volume>107</volume>
					<issue>2</issue>
					<fpage>346</fpage>
					<lpage>354</lpage>
					<pub-id pub-id-type="doi">10.1161/01.cir.0000048893.62841.f7</pub-id>
				</element-citation>
			</ref>
			<ref id="B4">
				<label>4</label>
				<mixed-citation>4. Shen MJ, Arora R, Jalife J. Atrial Myopathy. JACC Basic Transl Sci. 2019;4(5):640-54. doi: 10.1016/j.jacbts.2019.05.005.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Shen</surname>
							<given-names>MJ</given-names>
						</name>
						<name>
							<surname>Arora</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Jalife</surname>
							<given-names>J</given-names>
						</name>
					</person-group>
					<article-title>Atrial Myopathy</article-title>
					<source>JACC Basic Transl Sci</source>
					<year>2019</year>
					<volume>4</volume>
					<issue>5</issue>
					<fpage>640</fpage>
					<lpage>654</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jacbts.2019.05.005</pub-id>
				</element-citation>
			</ref>
			<ref id="B5">
				<label>5</label>
				<mixed-citation>5. Luo T, Chang CX, Zhou X, Gu SK, Jiang TM, Li YM. Characterization of Atrial Histopathological and Electrophysiological Changes in a Mouse Model of aging. Int J Mol Med. 2013;31(1):138-46. doi: 10.3892/ijmm.2012.1174.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Luo</surname>
							<given-names>T</given-names>
						</name>
						<name>
							<surname>Chang</surname>
							<given-names>CX</given-names>
						</name>
						<name>
							<surname>Zhou</surname>
							<given-names>X</given-names>
						</name>
						<name>
							<surname>Gu</surname>
							<given-names>SK</given-names>
						</name>
						<name>
							<surname>Jiang</surname>
							<given-names>TM</given-names>
						</name>
						<name>
							<surname>Li</surname>
							<given-names>YM</given-names>
						</name>
					</person-group>
					<article-title>Characterization of Atrial Histopathological and Electrophysiological Changes in a Mouse Model of aging</article-title>
					<source>Int J Mol Med</source>
					<year>2013</year>
					<volume>31</volume>
					<issue>1</issue>
					<fpage>138</fpage>
					<lpage>146</lpage>
					<pub-id pub-id-type="doi">10.3892/ijmm.2012.1174</pub-id>
				</element-citation>
			</ref>
			<ref id="B6">
				<label>6</label>
				<mixed-citation>6. Lin YK, Chen YA, Lee TI, Chen YC, Chen SA, Chen YJ. Aging Modulates the Substrate and Triggers Remodeling in Atrial Fibrillation. Circ J. 2018;82(5):1237-44. doi: 10.1253/circj.CJ-17-0242.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lin</surname>
							<given-names>YK</given-names>
						</name>
						<name>
							<surname>Chen</surname>
							<given-names>YA</given-names>
						</name>
						<name>
							<surname>Lee</surname>
							<given-names>TI</given-names>
						</name>
						<name>
							<surname>Chen</surname>
							<given-names>YC</given-names>
						</name>
						<name>
							<surname>Chen</surname>
							<given-names>SA</given-names>
						</name>
						<name>
							<surname>Chen</surname>
							<given-names>YJ</given-names>
						</name>
					</person-group>
					<article-title>Aging Modulates the Substrate and Triggers Remodeling in Atrial Fibrillation</article-title>
					<source>Circ J</source>
					<year>2018</year>
					<volume>82</volume>
					<issue>5</issue>
					<fpage>1237</fpage>
					<lpage>1244</lpage>
					<pub-id pub-id-type="doi">10.1253/circj.CJ-17-0242</pub-id>
				</element-citation>
			</ref>
			<ref id="B7">
				<label>7</label>
				<mixed-citation>7. Bisbal F, Baranchuk A, Braunwald E, Luna AB, Bayés-Genís A. Atrial Failure as a Clinical Entity: JACC Review Topic of the Week. J Am Coll Cardiol. 2020;75(2):222-32. doi: 10.1016/j.jacc.2019.11.013.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Bisbal</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Baranchuk</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Braunwald</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Luna</surname>
							<given-names>AB</given-names>
						</name>
						<name>
							<surname>Bayés-Genís</surname>
							<given-names>A</given-names>
						</name>
					</person-group>
					<article-title>Atrial Failure as a Clinical Entity: JACC Review Topic of the Week</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2020</year>
					<volume>75</volume>
					<issue>2</issue>
					<fpage>222</fpage>
					<lpage>232</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jacc.2019.11.013</pub-id>
				</element-citation>
			</ref>
			<ref id="B8">
				<label>8</label>
				<mixed-citation>8. Abhayaratna WP, Seward JB, Appleton CP, Douglas PS, Oh JK, Tajik AJ, et al. Left Atrial Size: Physiologic Determinants and Clinical Applications. J Am Coll Cardiol. 2006;47(12):2357-63. doi: 10.1016/j.jacc.2006.02.048.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Abhayaratna</surname>
							<given-names>WP</given-names>
						</name>
						<name>
							<surname>Seward</surname>
							<given-names>JB</given-names>
						</name>
						<name>
							<surname>Appleton</surname>
							<given-names>CP</given-names>
						</name>
						<name>
							<surname>Douglas</surname>
							<given-names>PS</given-names>
						</name>
						<name>
							<surname>Oh</surname>
							<given-names>JK</given-names>
						</name>
						<name>
							<surname>Tajik</surname>
							<given-names>AJ</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Left Atrial Size: Physiologic Determinants and Clinical Applications</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2006</year>
					<volume>47</volume>
					<issue>12</issue>
					<fpage>2357</fpage>
					<lpage>2363</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jacc.2006.02.048</pub-id>
				</element-citation>
			</ref>
			<ref id="B9">
				<label>9</label>
				<mixed-citation>9. 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: 10.1016/j.echo.2016.01.011.</mixed-citation>
				<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>et al</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>
					<pub-id pub-id-type="doi">10.1016/j.echo.2016.01.011</pub-id>
				</element-citation>
			</ref>
			<ref id="B10">
				<label>10</label>
				<mixed-citation>10. Kupczynska K, Mandoli GE, Cameli M, Kasprzak JD. Left Atrial Strain - A Current Clinical Perspective. Kardiol Pol. 2021;79(9):955-64. doi: 10.33963/KP.a2021.0105.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Kupczynska</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>Mandoli</surname>
							<given-names>GE</given-names>
						</name>
						<name>
							<surname>Cameli</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Kasprzak</surname>
							<given-names>JD</given-names>
						</name>
					</person-group>
					<article-title>Left Atrial Strain - A Current Clinical Perspective</article-title>
					<source>Kardiol Pol</source>
					<year>2021</year>
					<volume>79</volume>
					<issue>9</issue>
					<fpage>955</fpage>
					<lpage>964</lpage>
					<pub-id pub-id-type="doi">10.33963/KP.a2021.0105</pub-id>
				</element-citation>
			</ref>
			<ref id="B11">
				<label>11</label>
				<mixed-citation>11. Mandoli GE, D'Ascenzi F, Vinco G, Benfari G, Ricci F, Focardi M, et al. Novel Approaches in Cardiac Imaging for Non-invasive Assessment of Left Heart Myocardial Fibrosis. Front Cardiovasc Med. 2021;8:614235. doi: 10.3389/fcvm.2021.614235.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Mandoli</surname>
							<given-names>GE</given-names>
						</name>
						<name>
							<surname>D'Ascenzi</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Vinco</surname>
							<given-names>G</given-names>
						</name>
						<name>
							<surname>Benfari</surname>
							<given-names>G</given-names>
						</name>
						<name>
							<surname>Ricci</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Focardi</surname>
							<given-names>M</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Novel Approaches in Cardiac Imaging for Non-invasive Assessment of Left Heart Myocardial Fibrosis</article-title>
					<source>Front Cardiovasc Med</source>
					<year>2021</year>
					<volume>8</volume>
					<size units="pages">614235</size>
					<pub-id pub-id-type="doi">10.3389/fcvm.2021.614235</pub-id>
				</element-citation>
			</ref>
			<ref id="B12">
				<label>12</label>
				<mixed-citation>12. Cameli M, Lisi M, Righini FM, Massoni A, Natali BM, Focardi M, et al. Usefulness of Atrial Deformation Analysis to Predict Left Atrial Fibrosis and Endocardial Thickness in Patients Undergoing Mitral Valve Operations for Severe Mitral Regurgitation Secondary to Mitral Valve Prolapse. Am J Cardiol. 2013;111(4):595-601. doi: 10.1016/j.amjcard.2012.10.049.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Cameli</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Lisi</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Righini</surname>
							<given-names>FM</given-names>
						</name>
						<name>
							<surname>Massoni</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Natali</surname>
							<given-names>BM</given-names>
						</name>
						<name>
							<surname>Focardi</surname>
							<given-names>M</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Usefulness of Atrial Deformation Analysis to Predict Left Atrial Fibrosis and Endocardial Thickness in Patients Undergoing Mitral Valve Operations for Severe Mitral Regurgitation Secondary to Mitral Valve Prolapse</article-title>
					<source>Am J Cardiol</source>
					<year>2013</year>
					<volume>111</volume>
					<issue>4</issue>
					<fpage>595</fpage>
					<lpage>601</lpage>
					<pub-id pub-id-type="doi">10.1016/j.amjcard.2012.10.049</pub-id>
				</element-citation>
			</ref>
			<ref id="B13">
				<label>13</label>
				<mixed-citation>13. Vieira MJ, Teixeira R, Gonçalves L, Gersh BJ. Left Atrial Mechanics: Echocardiographic Assessment and Clinical Implications. J Am Soc Echocardiogr. 2014;27(5):463-78. doi: 10.1016/j.echo.2014.01.021.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Vieira</surname>
							<given-names>MJ</given-names>
						</name>
						<name>
							<surname>Teixeira</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Gonçalves</surname>
							<given-names>L</given-names>
						</name>
						<name>
							<surname>Gersh</surname>
							<given-names>BJ</given-names>
						</name>
					</person-group>
					<article-title>Left Atrial Mechanics: Echocardiographic Assessment and Clinical Implications</article-title>
					<source>J Am Soc Echocardiogr</source>
					<year>2014</year>
					<volume>27</volume>
					<issue>5</issue>
					<fpage>463</fpage>
					<lpage>478</lpage>
					<pub-id pub-id-type="doi">10.1016/j.echo.2014.01.021</pub-id>
				</element-citation>
			</ref>
			<ref id="B14">
				<label>14</label>
				<mixed-citation>14. Cameli M, Sparla S, Losito M, Righini FM, Menci D, Lisi M, et al. Correlation of Left Atrial Strain and Doppler Measurements with Invasive Measurement of Left Ventricular End-Diastolic Pressure in Patients Stratified for Different Values of Ejection Fraction. Echocardiography. 2016;33(3):398-405. doi: 10.1111/echo.13094.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Cameli</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Sparla</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Losito</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Righini</surname>
							<given-names>FM</given-names>
						</name>
						<name>
							<surname>Menci</surname>
							<given-names>D</given-names>
						</name>
						<name>
							<surname>Lisi</surname>
							<given-names>M</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Correlation of Left Atrial Strain and Doppler Measurements with Invasive Measurement of Left Ventricular End-Diastolic Pressure in Patients Stratified for Different Values of Ejection Fraction</article-title>
					<source>Echocardiography</source>
					<year>2016</year>
					<volume>33</volume>
					<issue>3</issue>
					<fpage>398</fpage>
					<lpage>405</lpage>
					<pub-id pub-id-type="doi">10.1111/echo.13094</pub-id>
				</element-citation>
			</ref>
			<ref id="B15">
				<label>15</label>
				<mixed-citation>15. Morris DA, Belyavskiy E, Aravind-Kumar R, Kropf M, Frydas A, Braunauer K, et al. Potential Usefulness and Clinical Relevance of Adding Left Atrial Strain to Left Atrial Volume Index in the Detection of Left Ventricular Diastolic Dysfunction. JACC Cardiovasc Imaging. 2018;11(10):1405-15. doi: 10.1016/j.jcmg.2017.07.029.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Morris</surname>
							<given-names>DA</given-names>
						</name>
						<name>
							<surname>Belyavskiy</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Aravind-Kumar</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Kropf</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Frydas</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Braunauer</surname>
							<given-names>K</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Potential Usefulness and Clinical Relevance of Adding Left Atrial Strain to Left Atrial Volume Index in the Detection of Left Ventricular Diastolic Dysfunction</article-title>
					<source>JACC Cardiovasc Imaging</source>
					<year>2018</year>
					<volume>11</volume>
					<issue>10</issue>
					<fpage>1405</fpage>
					<lpage>1415</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jcmg.2017.07.029</pub-id>
				</element-citation>
			</ref>
			<ref id="B16">
				<label>16</label>
				<mixed-citation>16. Cameli M, Lisi M, Focardi M, Reccia R, Natali BM, Sparla S, et al. Left Atrial Deformation Analysis by Speckle Tracking Echocardiography for Prediction of Cardiovascular Outcomes. Am J Cardiol. 2012;110(2):264-9. doi: 10.1016/j.amjcard.2012.03.022.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Cameli</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Lisi</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Focardi</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Reccia</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Natali</surname>
							<given-names>BM</given-names>
						</name>
						<name>
							<surname>Sparla</surname>
							<given-names>S</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Left Atrial Deformation Analysis by Speckle Tracking Echocardiography for Prediction of Cardiovascular Outcomes</article-title>
					<source>Am J Cardiol</source>
					<year>2012</year>
					<volume>110</volume>
					<issue>2</issue>
					<fpage>264</fpage>
					<lpage>269</lpage>
					<pub-id pub-id-type="doi">10.1016/j.amjcard.2012.03.022</pub-id>
				</element-citation>
			</ref>
			<ref id="B17">
				<label>17</label>
				<mixed-citation>17. Kim D, Seo JH, Choi KH, Lee SH, Choi JO, Jeon ES, et al. Prognostic Implications of Left Atrial Stiffness Index in Heart Failure Patients with Preserved Ejection Fraction. JACC Cardiovasc Imaging. 2023;16(4):435-45. doi: 10.1016/j.jcmg.2022.11.002.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Kim</surname>
							<given-names>D</given-names>
						</name>
						<name>
							<surname>Seo</surname>
							<given-names>JH</given-names>
						</name>
						<name>
							<surname>Choi</surname>
							<given-names>KH</given-names>
						</name>
						<name>
							<surname>Lee</surname>
							<given-names>SH</given-names>
						</name>
						<name>
							<surname>Choi</surname>
							<given-names>JO</given-names>
						</name>
						<name>
							<surname>Jeon</surname>
							<given-names>ES</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Prognostic Implications of Left Atrial Stiffness Index in Heart Failure Patients with Preserved Ejection Fraction</article-title>
					<source>JACC Cardiovasc Imaging</source>
					<year>2023</year>
					<volume>16</volume>
					<issue>4</issue>
					<fpage>435</fpage>
					<lpage>445</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jcmg.2022.11.002</pub-id>
				</element-citation>
			</ref>
			<ref id="B18">
				<label>18</label>
				<mixed-citation>18. Russo C, Jin Z, Homma S, Rundek T, Elkind MSV, Sacco RL, et al. LA Phasic Volumes and Reservoir Function in the Elderly by Real-Time 3D Echocardiography: Normal Values, Prognostic Significance, and Clinical Correlates. JACC Cardiovasc Imaging. 2017;10(9):976-85. doi: 10.1016/j.jcmg.2016.07.015.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Russo</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Jin</surname>
							<given-names>Z</given-names>
						</name>
						<name>
							<surname>Homma</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Rundek</surname>
							<given-names>T</given-names>
						</name>
						<name>
							<surname>Elkind</surname>
							<given-names>MSV</given-names>
						</name>
						<name>
							<surname>Sacco</surname>
							<given-names>RL</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>LA Phasic Volumes and Reservoir Function in the Elderly by Real-Time 3D Echocardiography: Normal Values, Prognostic Significance, and Clinical Correlates</article-title>
					<source>JACC Cardiovasc Imaging</source>
					<year>2017</year>
					<volume>10</volume>
					<issue>9</issue>
					<fpage>976</fpage>
					<lpage>985</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jcmg.2016.07.015</pub-id>
				</element-citation>
			</ref>
			<ref id="B19">
				<label>19</label>
				<mixed-citation>19. Henein MY, Lindqvist P. Diastolic Function Assessment by Echocardiography: A Practical Manual for Clinical Use and Future Applications. Echocardiography. 2020;37(11):1908-18. doi: 10.1111/echo.14698.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Henein</surname>
							<given-names>MY</given-names>
						</name>
						<name>
							<surname>Lindqvist</surname>
							<given-names>P</given-names>
						</name>
					</person-group>
					<article-title>Diastolic Function Assessment by Echocardiography: A Practical Manual for Clinical Use and Future Applications</article-title>
					<source>Echocardiography</source>
					<year>2020</year>
					<volume>37</volume>
					<issue>11</issue>
					<fpage>1908</fpage>
					<lpage>1918</lpage>
					<pub-id pub-id-type="doi">10.1111/echo.14698</pub-id>
				</element-citation>
			</ref>
			<ref id="B20">
				<label>20</label>
				<mixed-citation>20. Sugimoto T, Robinet S, Dulgheru R, Bernard A, Ilardi F, Contu L, et al. Echocardiographic Reference Ranges for Normal Left Atrial Function Parameters: Results from the EACVI NORRE Study. Eur Heart J Cardiovasc Imaging. 2018;19(6):630-8. doi: 10.1093/ehjci/jey018.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Sugimoto</surname>
							<given-names>T</given-names>
						</name>
						<name>
							<surname>Robinet</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Dulgheru</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Bernard</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Ilardi</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Contu</surname>
							<given-names>L</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Echocardiographic Reference Ranges for Normal Left Atrial Function Parameters: Results from the EACVI NORRE Study</article-title>
					<source>Eur Heart J Cardiovasc Imaging</source>
					<year>2018</year>
					<volume>19</volume>
					<issue>6</issue>
					<fpage>630</fpage>
					<lpage>638</lpage>
					<pub-id pub-id-type="doi">10.1093/ehjci/jey018</pub-id>
				</element-citation>
			</ref>
			<ref id="B21">
				<label>21</label>
				<mixed-citation>21. Nyberg J, Jakobsen EO, Østvik A, Holte E, Stølen S, Lovstakken L, et al. Echocardiographic Reference Ranges of Global Longitudinal Strain for All Cardiac Chambers Using Guideline-Directed Dedicated Views. JACC Cardiovasc Imaging. 2023;16(12):1516-31. doi: 10.1016/j.jcmg.2023.08.011.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Nyberg</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Jakobsen</surname>
							<given-names>EO</given-names>
						</name>
						<name>
							<surname>Østvik</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Holte</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Stølen</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Lovstakken</surname>
							<given-names>L</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Echocardiographic Reference Ranges of Global Longitudinal Strain for All Cardiac Chambers Using Guideline-Directed Dedicated Views</article-title>
					<source>JACC Cardiovasc Imaging</source>
					<year>2023</year>
					<volume>16</volume>
					<issue>12</issue>
					<fpage>1516</fpage>
					<lpage>1531</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jcmg.2023.08.011</pub-id>
				</element-citation>
			</ref>
			<ref id="B22">
				<label>22</label>
				<mixed-citation>22. Inciardi RM, Claggett B, Minamisawa M, Shin SH, Selvaraj S, Gonçalves A, et al. Association of Left Atrial Structure and Function with Heart Failure in Older Adults. J Am Coll Cardiol. 2022;79(16):1549-61. doi: 10.1016/j.jacc.2022.01.053.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Inciardi</surname>
							<given-names>RM</given-names>
						</name>
						<name>
							<surname>Claggett</surname>
							<given-names>B</given-names>
						</name>
						<name>
							<surname>Minamisawa</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Shin</surname>
							<given-names>SH</given-names>
						</name>
						<name>
							<surname>Selvaraj</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Gonçalves</surname>
							<given-names>A</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Association of Left Atrial Structure and Function with Heart Failure in Older Adults</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2022</year>
					<volume>79</volume>
					<issue>16</issue>
					<fpage>1549</fpage>
					<lpage>1561</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jacc.2022.01.053</pub-id>
				</element-citation>
			</ref>
		</ref-list>
		<fn-group>
			<fn fn-type="other">
				<label/>
				<p>Study Association</p>
				<p>This study is not associated with any thesis or dissertation work.</p>
			</fn>
			<fn fn-type="other">
				<label/>
				<p>Ethics Approval and Consent to Participate</p>
				<p>This article does not contain any studies with human participants or animals performed by any of the authors.</p>
			</fn>
		</fn-group>
		<fn-group>
			<fn fn-type="financial-disclosure">
				<p>Sources of Funding: There were no external funding sources for this study.</p>
			</fn>
		</fn-group>
	</back>
	<sub-article article-type="translation" id="TRpt" xml:lang="pt">
		<front-stub>
			<article-id pub-id-type="doi">10.36660/abcimg.20240043</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Artigo de Revisão</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Envelhecimento E Análise Ecocardiográfica Funcional do Átrio Esquerdo</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<name>
						<surname>Oliveira</surname>
						<given-names>Fernando Rodrigues da Camara</given-names>
					</name>
					<role>Concepção e desenho da pesquisa e revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<role>Obtenção de dados</role>
					<role>análise e interpretação dos dados e redação do manuscrito</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
					<xref ref-type="aff" rid="aff2002"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0002-8891-057X</contrib-id>
					<name>
						<surname>Resende</surname>
						<given-names>Marcos Valerio Coimbra de</given-names>
					</name>
					<role>Concepção e desenho da pesquisa e revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff2002"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Vieira</surname>
						<given-names>Marcelo Luiz Campos</given-names>
					</name>
					<role>Concepção e desenho da pesquisa e revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff2002"><sup>2</sup></xref>
					<xref ref-type="aff" rid="aff3002"><sup>3</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff1002">
				<label>1</label>
				<country country="BR">Brasil</country>
				<institution content-type="original">Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brasil</institution>
			</aff>
			<aff id="aff2002">
				<label>2</label>
				<country country="BR">Brasil</country>
				<institution content-type="original">Hospital Israelita Albert Einstein, São Paulo, SP – Brasil</institution>
			</aff>
			<aff id="aff3002">
				<label>3</label>
				<country country="BR">Brasil</country>
				<institution content-type="original">Universidade de São Paulo, Instituto do Coração, São Paulo, SP – Brasil</institution>
			</aff>
			<author-notes>
				<corresp id="c01002"> Correspondência: Fernando Rodrigues da Camara Oliveira • Hospital Israelita Albert Einstein. Avenida Albert Einstein, 627. CEP: 05652-900. São Paulo, SP – Brasil E-mail: fernandocamaracardio@gmail.com </corresp>
				<fn fn-type="conflict">
					<p>Potencial Conflito de Interesse</p>
					<p>Declaro não haver conflito de interesses pertinentes.</p>
				</fn>
				<fn fn-type="edited-by">
					<p>Editor responsável pela revisão: Marcelo Dantas</p>
				</fn>
			</author-notes>
			
			<abstract>
				<title>Resumo</title>
				<p>As doenças cardiovasculares (DCV) são a principal causa de morte no Brasil, com o envelhecimento sendo um grande fator de risco. Estudos indicam que a prevalência de DCV aumenta com a idade, afetando a hipertrofia ventricular, disfunção diastólica e fibrilação atrial. A miopatia atrial, relacionada ao envelhecimento, tem sido mais estudada, com o estresse oxidativo e a inflamação crônica sendo investigados como agentes causadores desse processo. A função atrial esquerda tem sido mais analisada com destaque para seu papel na performance cardíaca. Técnicas atuais de análise ecocardiográfica, como o <italic>speckle</italic> tracking, permitem uma avaliação detalhada da função atrial, mostrando vantagens em relação à análise do volume atrial máximo. Estudos revelam a importância do <italic>strain</italic> atrial na previsão de eventos cardiovasculares. Com o envelhecimento, há uma redução progressiva das funções atriais, e novas medidas estão sendo desenvolvidas para detectar precocemente a disfunção atrial, o que pode impactar as futuras diretrizes e a definição dos padrões normais relacionados à idade.</p>
			</abstract>
			<kwd-group xml:lang="pt">
				<kwd>função atrial, remodelamento atrial</kwd>
				<kwd>ecocardiografia</kwd>
				<kwd>envelhecimento</kwd>
			</kwd-group>
		</front-stub>
		<body>
			
				<p>
					<fig id="f01002">
						<label>Figura Central</label>
						<caption>
							<title>: Envelhecimento E Análise Ecocardiográfica Funcional do Átrio Esquerdo</title>
							<p>Exemplo de análise do strain atrial esquerdo nos cortes apicais de 4 e 2 câmaras com o software Echopac® (GE), utilizando o complexo QRS como referência para aferição. S_CD: strain de conduto; S_CT: strain de contração atrial; S_R: strain de reservatório. Notam-se os valores por corte e o valor médio considerando todos os seguimentos atriais.</p>
						</caption>
						<graphic xlink:href="2675-312X-abcimg-37-03-e20240043-gf01-pt.tif"/>
					</fig>
				</p>
			
			<sec sec-type="intro">
				<title>Introdução</title>
				<p>As doenças cardiovasculares (DCV) são a principal causa de morte no Brasil, e o processo de envelhecimento é um dos principais fatores de risco para DCV. A prevalência de DCV aumenta com a idade, independentemente do gênero.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Um estudo publicado em 2019<sup><xref ref-type="bibr" rid="B2">2</xref></sup> mostrou que a chance de um indivíduo com 65 anos ou mais ter DCV é 4,7 vezes maior no Brasil. Dados derivados do estudo BLSA (The Framingham Heart Study and the Baltimore Longitudinal Study on Aging)<sup><xref ref-type="bibr" rid="B3">3</xref></sup> indicam que o envelhecimento em indivíduos sem DCV concomitantes está relacionado a aumento da hipertrofia ventricular, disfunção diastólica, declínio da aptidão física e aumento da prevalência de fibrilação atrial.</p>
				<p>Atualmente, a participação da função atrial esquerda no processo da morbidade cardiovascular vem sendo mais estudada, e a miopatia atrial foi reconhecida como uma entidade independente, com o processo de envelhecimento sendo uma de suas principais causas.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Modelos animais demonstraram que o envelhecimento está relacionado a alterações estruturais e das propriedades eletrofisiológicas atriais.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Estresse oxidativo, desregulação do cálcio, e inflamação crônica, levando à via final da fibrose,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> têm sido investigados como agentes importantes deste processo. O átrio doente reúne condições que predispõem à estase sanguínea e disfunção endotelial, favorecendo a ocorrência dos fenômenos embólicos.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
				<p>Além do reconhecimento da miopatia atrial enquanto causadora da clássica relação entre fibrilação atrial e fenômenos cardioembólicos, o prejuízo da função atrial <italic>per se</italic> também vem sendo mais bem compreendido, a ponto de hoje falar-se em insuficiência atrial enquanto entidade clínica – definida como qualquer disfunção atrial (anatômica, mecânica, elétrica e/ou reológica) causando prejuízo à performance cardíaca e sintomas.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> O átrio esquerdo (AE) desempenha um papel fundamental no enchimento ventricular. A fisiologia do AE pode ser estudada e melhor determinada a partir da análise das diferentes fases da sua contribuição para o enchimento ventricular, observadas como fase de reservatório, conduto e contração atrial. A capacidade de reservatório atrial, ao encher-se durante a sístole ventricular a partir das veias pulmonares, corresponde a 40 a 50% do volume sistólico. A transferência passiva durante a diástole ventricular (função de conduto), por 20 a 30%. A contração ativa do átrio transfere então o volume restante. A redução da função atrial em qualquer uma dessas fases pode prejudicar a performance cardíaca global e levar a piores desfechos.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
				<sec>
					<title>Análise Ecocardiográfica da Função Atrial Esquerda</title>
					<p>A medida biplanar do volume atrial esquerdo máximo indexado (LAViMax) é a técnica mais comumente utilizada e recomendada pelas diretrizes para a avaliação estrutural do átrio. Trata-se de um parâmetro, em geral, de fácil aquisição, cuja relação com desfechos em pacientes com fração de ejeção preservada e reduzida está bem documentada. O volume atrial máximo pode ser interpretado como o resultado acumulativo dos processos que resultam na miopatia atrial ao longo do tempo. Estudos observacionais com mais de 6 mil pacientes demonstraram que um volume máximo indexado ≥ 34 ml/m<sup>2</sup> é um preditor independente de morte, insuficiência cardíaca (IC), fibrilação atrial e acidente vascular cerebral isquêmico.<sup><xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup> Entretanto, o desenvolvimento de novas técnicas de imagem cardiovascular permitiu uma análise mais detalhada não apenas da estrutura, mas também das características funcionais do AE.</p>
					<p>O desenvolvimento da técnica de <italic>speckle tracking</italic> permitiu analisar a deformação miocárdica atrial durante todo o ciclo cardíaco de maneira mais rápida e reprodutível, principalmente devido à sua independência em relação ao ângulo de insonação. Atualmente, é possível quantificar, por meio de <italic>softwares</italic> dedicados, a função atrial de pico ou reservatório (PALS ou LAS-r), conduto (LAS-cd), e contração atrial (LAS-ct)<sup><xref ref-type="bibr" rid="B10">10</xref></sup> a partir da análise semiautomatizada de imagens apicais em duas e quatro câmaras focadas no AE (<xref ref-type="fig" rid="f01002">Figura Central</xref>). Foi demonstrado que a análise da função atrial, especialmente de reservatório, apresenta importantes vantagens em relação à análise resumida na quantificação do volume atrial máximo, visto que as alterações funcionais ocorrem antes que as estruturais possam ser detectadas.<sup><xref ref-type="bibr" rid="B11">11</xref></sup></p>
					<p>Estudos demonstraram uma importante correlação entre a redução do LAS-r e a presença de fibrose atrial avaliada por ressonância magnética e estudo anatomopatológico.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> Um interessante trabalho<sup><xref ref-type="bibr" rid="B12">12</xref></sup> analisou o <italic>strain</italic> atrial pré-operatório de 46 pacientes com prolapso mitral encaminhados para cirurgia cardíaca e que tiveram amostras atriais histológicas coletadas. O LAS-r apresentou uma correlação significativa com o grau de fibrose no estudo anatomopatológico (r = - 0,82, p &lt; 0,0001). Em contrapartida, o volume atrial, a fração de ejeção atrial e os parâmetros derivados do Doppler (relação E/e’) apresentaram uma correlação fraca.</p>
					<p>A análise da mecânica atrial reflete também a importante interação atrioventricular, tendo em vista que a distensão atrial durante a sístole é influenciada pelo movimento do anel mitral, além da complacência ventricular também interferir no processo de esvaziamento atrial (passivo e ativo).<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Dessa maneira, o <italic>strain</italic> atrial também é um importante parâmetro para a análise da função ventricular. Um estudo<sup><xref ref-type="bibr" rid="B14">14</xref></sup> com 80 pacientes encaminhados para cateterismo cardíaco demonstrou que, entre os pacientes com fração de ejeção ≤ 30%, um valor de LAS-r &lt; 18% apresentou acurácia superior à relação E/e’ para predizer uma pressão diastólica final do ventrículo esquerdo superior a 12 mmHg.</p>
					<p>A relação íntima entre a mecânica atrial e ventricular também pode ser demonstrada pelo valor adicional da análise do <italic>strain</italic> atrial no diagnóstico de disfunção diastólica, podendo contribuir para a redução do diagnóstico frequente de “função diastólica indeterminada” conforme as diretrizes atuais da Sociedade Americana de Ecocardiografia (ASE).<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Entre 517 pacientes considerados em risco de desenvolver disfunção diastólica (portadores de hipertensão arterial, diabetes ou história de doença coronariana),<sup><xref ref-type="bibr" rid="B15">15</xref></sup> foi observado que a redução do LAS-r foi mais comum do que o aumento do LAVI (36,9% vs. 15,5%; p &lt; 0,01) e que 29,4% dos pacientes com LAViMax normal apresentavam LAS-r reduzido. Nesta população, a adição do valor de LAS-r &lt; 23% como parâmetro diagnóstico adicional de disfunção diastólica, além dos critérios determinados pela ASE, aumentou a detecção de disfunção diastólica de 13,5% para 23,4% (p &lt; 0,01). Além disso, LAS-r &lt; 23% associou-se a uma pior classe funcional NYHA (New York Heart Association), mesmo quando o LAViMax encontrava-se normal.</p>
					<p>Considerando a capacidade de detectar precocemente alterações funcionais atriais e ventriculares, o valor prognóstico do <italic>strain</italic> atrial tem sido comprovado em diversos contextos clínicos. Um estudo prospectivo com 312 pacientes<sup><xref ref-type="bibr" rid="B16">16</xref></sup> demonstrou que o LAS-r apresentou a melhor capacidade (área sob a curva: 0,83) para prever, em 3,1 ± 1,4 anos, a ocorrência de fibrilação atrial, IC, acidente vascular cerebral, ataque isquêmico transitório, infarto do miocárdio, revascularização coronariana e morte cardiovascular, em relação ao LAVI (área sob a curva: 0,71).</p>
					<p>A análise do <italic>strain</italic> atrial também permite a avaliação não invasiva do índice de rigidez atrial (LASI), que é definido como a relação entre E/e’ média e o LAS-r. A rigidez atrial elevada resulta da exposição crônica do AE a pressões elevadas de enchimento. Isso indica uma redução na complacência atrial, com variações volumétricas resultando em grande aumento das pressões atriais. Um estudo avaliou retrospectivamente 307 pacientes<sup><xref ref-type="bibr" rid="B17">17</xref></sup> com aumento da medida invasiva da pressão final de enchimento ventricular (≥ 16 mmHg) e que foram submetidos a um ecocardiograma em um intervalo de até 7 dias. Nesta população, um LASI &gt; 0,26 apresentou uma melhor performance (área sob a curva: 0,743; IC de 95%: 0,681-0,806) para predizer morte por qualquer causa ou hospitalização por IC em relação aos parâmetros clássicos de análise da função diastólica (E/e’ média, velocidade da regurgitação tricúspide e LAViMax).</p>
					<p>Dados volumétricos também continuam a ser explorados. A partir da ecocardiografia tridimensional ou das curvas do <italic>strain</italic> atrial, também é possível quantificar de maneira mais fácil a variação do volume atrial esquerdo durante todo o ciclo cardíaco, não se limitando à medida isolada do volume máximo ao final da sístole como feito habitualmente. Em uma população idosa (71 ± 9 anos) demostrou-se que o volume mínimo ao final da diástole, não o máximo, apresenta maior associação a eventos cardiovasculares, possivelmente por representar o momento do ciclo cardíaco em que o átrio está mais exposto às pressões de enchimento ventricular.<sup><xref ref-type="bibr" rid="B18">18</xref></sup></p>
				</sec>
				<sec>
					<title>Função Atrial Esquerda e Envelhecimento</title>
					<p>Estudos recentes têm sido realizados para estabelecer os valores normais do <italic>strain</italic> atrial, considerando sua variação conforme a idade. É bem conhecida a inversão progressiva na relação entre o enchimento ventricular rápido e a contração atrial à medida que os indivíduos envelhecem. A partir da quinta década de vida, o relaxamento ventricular começa a ficar mais lento, prejudicando o enchimento ventricular precoce e aumentando compensatoriamente a fase tardia.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Curiosamente, dados derivados do estudo NORRE (<italic>Normal Reference Ranges for Echocardiography</italic>)<sup><xref ref-type="bibr" rid="B20">20</xref></sup> demostraram justamente uma redução progressiva com a idade nas funções de reservatório (LAS-r) e conduto (LAS-cd), com aumento concomitante na função de bomba (LAS-ct) e no índice de rigidez atrial. Os valores mínimos esperados para LAS -r foram de 31,1% para indivíduos entre 20 e 40 anos, 27,7% para aqueles entre 40 e 60 anos, e 22,7% para os com 60 anos ou mais. Em contrapartida, os valores mínimos para LAS-ct foram de 7,2%, 9,3% e 7,7%, respectivamente.</p>
					<p>Um estudo mais recente<sup><xref ref-type="bibr" rid="B21">21</xref></sup> baseado do HUNT4Echo (The Echocardiographic substudy of the 4th wave of the Trøndelag Health Study), que incluiu 1329 pacientes, também buscou estabelecer os valores normais para o <italic>strain</italic> atrial. Ao contrário do estudo NORRE, que utilizou o <italic>software</italic> VIS (Tomtec), os dados do HUNT4Echo foram analisados pelo Echopac (GE). Os resultados também demonstraram uma associação negativa entre idade e os <italic>strains</italic> de reservatório e conduto.</p>
					<p>Por fim, um estudo publicado na revista Journal of American College of Cardiology em abril de 2022 investigou especificamente o comportamento da estrutura e função atriais em pacientes idosos.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> No artigo de Inciardi et al., destaca-se inicialmente a medida do LAViMAx como a mais amplamente utilizada para avaliar o AE, sendo recomendada pelas principais sociedades internacionais de cardiologia. No entanto, ressalta-se a possibilidade de que novas medidas e análises funcionais com técnicas emergentes possam fornecer informações adicionais para o diagnóstico precoce da disfunção atrial, mesmo antes da detecção de alterações estruturais.</p>
					<p>Trata-se da análise de uma coorte multicêntrica de pacientes do estudo ARIC (Atherosclerosis Risk in Communities Study), utilizando novas medidas de avaliação do AE em uma população de 4901 participantes com idade acima de 65 anos, que apresentavam ritmo sinusal e não tinham IC. Os objetivos do estudo foram avaliar as variações nas medidas estruturais e funcionais do AE, além de investigar sua correlação com NT-proBNP e a incidência do desfecho combinado de morte ou IC em um seguimento prospectivo médio de 5,5 anos.</p>
					<p>Além da medida estrutural convencional do LAViMax, outras duas medidas foram realizadas: o volume mínimo do AE (LAViMin) e a fração de esvaziamento do AE (LAEF). Além disso, foram realizadas as medidas funcionais de reservatório, conduto e contrátil do AE derivadas do <italic>strain</italic> bidimensional. Curiosamente, uma coorte inicial de 301 pacientes livres de DCV prevalentes foi analisada para estabelecer os limites de normalidade dos parâmetros avaliados, definidos como os valores entre o 10<sup>o</sup>e 90<sup>o</sup>percentis.</p>
					<p>Após um período de seguimento médio de 5,5 anos e ajuste para fatores de confusão clínicos, função ventricular e NT-proBNP, com exceção do LAViMax, todos os demais parâmetros estruturais e funcionais analisados (inclusive o LAViMin) permaneceram significativamente associados a uma maior incidência do desfecho combinado. As variáveis foram identificadas como preditoras de evolução desfavorável, mesmo após exclusão de pacientes com aumento do LAViMax, ou quando os desfechos foram analisados separadamente entre os grupos de pacientes que evoluíram com IC de fração de ejeção reduzida ou preservada.</p>
					<p>Os <italic>strains</italic> atriais de reservatório e conduto apresentaram uma relação não linear dos desfechos, evidenciando um aumento significativo da incidência combinada de morte e IC com valores abaixo de 28% e 11%, respectivamente. Assim, a medida convencional da dimensão do AE mostrou-se como uma variável menos robusta nesta população idosa em comparação com a medida do volume atrial mínimo indexado e os parâmetros funcionais derivados do <italic>strain</italic> atrial. É importante salientar que os valores máximos de normalidade (percentil 90) para LAViMax nessa população foram de 37,8 ml/m<sup>2</sup>para mulheres e 42,7 ml/m<sup>2</sup>para homens, indicando que o valor normal para idosos é subestimado nas diretrizes atuais.</p>
				</sec>
			</sec>
			<sec sec-type="conclusions">
				<title>Conclusão</title>
				<p>O desenvolvimento de novas técnicas ecocardiográficas permitiu uma análise mais detalhada da função atrial esquerda. Ao combinar dados funcionais com análise estrutural, foi possível caracterizar a função atrial esquerda ao longo de todo ciclo cardíaco, estabelecer sua relação com a função ventricular esquerda e avaliar as modificações decorrentes de processos patológicos e do envelhecimento. Se antes o AE era visto como uma “câmara tampão” que reagia passivamente com a disfunção ventricular, a análise dos parâmetros dinâmicos revelou a precocidade da disfunção atrial, sua participação ativa na redução da performance cardíaca global e seu valor prognóstico em diversos contextos. Com o avanço tecnológico e métodos cada vez mais automatizados, incluindo o uso de inteligência artificial, espera-se uma maior disseminação e acessibilidade da análise funcional do AE. Novos estudos deverão incorporar tais achados às diretrizes e proporcionar uma melhor compreensão da variação esperada para os valores de normalidade decorrente do processo de envelhecimento.</p>
			</sec>
		</body>
		<back>
			<fn-group>
				<fn fn-type="other">
					<p>Vinculação Acadêmica</p>
					<p>Não há vinculação deste estudo a programas de pós-graduação.</p>
				</fn>
				<fn fn-type="other">
					<p>Aprovação Ética e Consentimento Informado</p>
					<p>Este artigo não contém estudos com humanos ou animais realizados por nenhum dos autores.</p>
				</fn>
			</fn-group>
			<fn-group>
				<fn fn-type="financial-disclosure">
					<p>Fontes de Financiamento: O presente estudo não teve fontes de financiamento externas.</p>
				</fn>
			</fn-group>
		</back>
	</sub-article>
</article>