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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">hFpwJ7mTdjPpkCLR4yryCzC</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2018000400312</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2018005004101</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20180040</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Mid-Term Results of Surgical Treatment of Atrial Fibrillation in Valvular Heart Disease Assesed by Speckle Tracking Echocardiography</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Lorenzo</surname>
            <given-names>Natalia</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mendez</surname>
            <given-names>Irene</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Taibo</surname>
            <given-names>Mikel</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Martinis</surname>
            <given-names>Gianfranco</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Badia</surname>
            <given-names>Sara</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Reyes</surname>
            <given-names>Guillermo</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Aguilar</surname>
            <given-names>Rio</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Hospital Universitario Infanta Cristina</institution>
        <addr-line>
          <city>Parla</city>
          <state>Madrid</state>
        </addr-line>
        <country country="ES">Spain</country>
        <institution content-type="original">Hospital Universitario Infanta Cristina, Parla, Madrid - Spain</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Hospital Universitario de La Princesa</institution>
        <addr-line>
          <state>Madrid</state>
        </addr-line>
        <country country="ES">Spain</country>
        <institution content-type="original">Hospital Universitario de La Princesa, Madrid - Spain</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Natalia Lorenzo Mu&#241;oz</bold>, Avenida 9 de junio, 2. 28981, Parla, Madrid - Spain. E-mail: <email>natalialorenzo84@gmail.com</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research, Analysis and interpretation of the data, Statistical analysis and Critical revision of the manuscript for intellectual content: Lorenzo N, Aguilar R; Acquisition of data: Lorenzo N, Mendez I, Taibo M, Martinis G, Badia S, Reyes G, Aguilar R; Writing of the manuscript: Lorenzo N.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub">
        <day>19</day>
        <month>03</month>
        <year>2018</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>04</month>
        <year>2018</year>
      </pub-date>
      <volume>110</volume>
      <issue>4</issue>
      <fpage>312</fpage>
      <lpage>320</lpage>
      <history>
        <date date-type="received">
          <day>24</day>
          <month>05</month>
          <year>2017</year>
        </date>
        <date date-type="rev-recd">
          <day>07</day>
          <month>07</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>10</day>
          <month>07</month>
          <year>2017</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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Atrial fibrillation frequently affects patients with valvular heart disease. Ablation of atrial fibrillation during valvular surgery is an alternative for restoring sinus rhythm.</p>
        </sec>
        <sec>
          <title>Objectives:</title>
          <p>This study aimed to evaluate mid-term results of successful atrial fibrillation surgical ablation during valvular heart disease surgery, to explore left atrium post-ablation mechanics and to identify predictors of recurrence.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>Fifty-three consecutive candidates were included. Eligibility criteria for ablation included persistent atrial fibrillation &lt;10 years and left atrium diameter &lt; 6.0 cm. Three months after surgery, echocardiogram, 24-hour Holter monitoring and electrocardiograms were performed in all candidates who maintained sinus rhythm (44 patients). Echo-study included left atrial deformation parameters (strain and strain rate), using 2-dimensional speckle-tracking echocardiography. Simultaneously, 30 healthy individuals (controls) were analyzed with the same protocol for left atrial performance. Significance was considered with a P value of &lt; 0.05.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>After a mean follow up of 17 &#177; 2 months, 13 new post-operative cases of recurrent atrial fibrillation were identified. A total of 1,245 left atrial segments were analysed. Left atrium was severely dilated in the post-surgery group and, mechanical properties of left atrium did not recover after surgery when compared with normal values. Left atrial volume (&#8805; 64 mL/m<sup>2</sup>) was the only independent predictor of atrial fibrillation recurrence (p = 0.03).</p>
        </sec>
        <sec>
          <title>Conclusions:</title>
          <p>Left atrial volume was larger in patients with atrial fibrillation recurrence and emerges as the main predictor of recurrences, thereby improving the selection of candidates for this therapy; however, no differences were found regarding myocardial deformation parameters. Despite electrical maintenance of sinus rhythm, left atrium mechanics did not recover after atrial fibrillation ablation performed during valvular heart disease surgery.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Ablation Techniques</kwd>
        <kwd>Atrial Fibrillation</kwd>
        <kwd>Heart Valve Diseases</kwd>
        <kwd>Cryosurgery</kwd>
        <kwd>Echocardiography</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Atrial fibrillation (AF) is a serious and frequent problem in valvular heart disease (VHD) affecting more than 30% of these patients. VHD leads to pressure and/or volume overload of the atria, especially in the left atrium (LA) in left-sided disease. AF is associated with higher morbidity and mortality in general population, but even more in VHD patients, requiring low threshold of anticoagulation because of higher risk of thromboembolism. AF also affects the decision making for selection of prosthesis type.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref>
			</p>
      <p>AF ablation during cardiac surgery has been demonstrated as a safe and effective procedure restoring sinus rhythm (SR). Although the original Cox-Maze procedure was described in patients with lone AF, its use has expanded to patients with associated organic heart disease.<xref ref-type="bibr" rid="B3">3</xref> According to some authors, success rates of the procedure can exceed 80%. However, there are few data on the results of this technique in valvular patients with persistent AF.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref>
			</p>
      <p>Myocardial strain and strain rate (strainR) represent the magnitude and rate, respectively, of myocardial deformation. Both atrial strain and strainR, obtained using either Doppler tissue imaging (DTI) or two-dimensional speckle-tracking echocardiography, have proved to be feasible and reproducible techniques to evaluate LA mechanics.<xref ref-type="bibr" rid="B6">6</xref>
			</p>
      <p>The aims of this study were to evaluate mid-term results after successful surgical ablation (SA) of AF in VHD patients, to explore LA mechanics using ultrasound strain and strainR imaging after SA of AF during VHD surgery and to identify clinical and echocardiographic predictors of recurrence during follow-up.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Patient eligibility</title>
        <p>We prospectively included candidates to surgical ablation, who underwent valvular heart surgery between May 2008 and May 2012 in our institution.</p>
        <p>Patient eligibility criteria for AF surgery included: persistent AF of less than ten years of evolution and left atrial anteroposterior (AP) diameter at preoperative transthoracic echocardiogram in long axis view of less than 6.0 cm.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref> All candidates were adequately informed and signed informed consent form for the procedure, according to the local ethics committee.</p>
        <p>Fifty-three consecutive candidates who underwent valvular heart surgery were included to surgical ablation.</p>
        <p>Success of AF ablation procedure was considered when patients maintained SR at the time of discharge. All these patients were selected for initial follow up. After rhythm stabilization, which is considered to occur at least 3 months after surgery,<xref ref-type="bibr" rid="B8">8</xref> an echocardiogram was scheduled, and ambulatory 24 hour Holter monitoring and electrocardiograms were systematically performed in all candidates who remained in SR (44 patients). Holter monitoring was programmed one month after the echocardiographic study, and electrocardiograms were made during clinical visits (at least two visits during the first year of follow up). Patients with persistent AF during the first 3 months after surgery were excluded from the follow-up.</p>
      </sec>
      <sec>
        <title>Surgical technique</title>
        <p>All the procedures were carried out by full sternotomy and extracorporeal circulation.</p>
        <p>Surgical technique for cryoablation was the same as previously described.<xref ref-type="bibr" rid="B9">9</xref> After aortic clamping, LA was opened when needed and left atrial appendage was ligated from its inside using a 3.0 monofilament suture. The cryoablation probe was placed for 60 s at a temperature between -100&#186;C and -160&#186;C. Lines were created surrounding pulmonary veins and also joining between these circles. Three more lines were performed: between the left pulmonary veins and the left appendage, between the left pulmonary veins and the P3 portion of the mitral annulus and between the tricuspid septal valve and the inferior cava.</p>
        <p>In cases where left atriotomy was not needed (in isolated aortic interventions), high-intensity-focused-ultrasound (HIFU - Epicor) cardiac ablation was used. Epicor Medical Cardiac Ablation System (St Jude) is designed to deliver HIFU via an entirely epicardial approach and consists of an array of transducers positioned after proper sizing around the LA wall of the pulmonary vein orifices.<xref ref-type="bibr" rid="B4">4</xref>
				</p>
      </sec>
      <sec>
        <title>Echocardiographic study</title>
        <p>A Vivid 7 Dimension ultrasound system (GE Healthcare) was used for the transthoracic echocardio graphic examination. All images and measurements were acquired with a MS4 matrix probe using the standard views according to the standards of the European Association of Echocardiography and the American Society of Echocardiography.<xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref>
				</p>
        <p>Strain parameters were obtained during ventricular systole (LASs - LA systolic strain) and diastole (LASa - LA diastolic strain), and strainR parameters were obtained during early (LASRe - LA strainR early) and late (LASRa - LA strainR late) ventricular diastole (<xref ref-type="fig" rid="f1">Figure 1</xref>) in 2 standard echo-views (apical 4- and 2-chamber views), using speckle-tracking echocardiography to avoid the angle-dependence of DTI.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>
				</p>
        <p>
          <fig id="f1">
            <label>Figure 1</label>
            <caption>
              <title>Left atrial phasic functions and their relationship with the cardiac cycle. Strain and strain rate curves are shown. During left ventricular (LV) systole and isovolumetric relaxation, left atrium (LA) works as a distensible reservoir accommodating blood flow from the pulmonary veins. During early LV diastole, LA behaves as a conduit that starts with mitral valve opening and terminates before LA contraction, allowing passive emptying during early ventricular diastole and diastasis. Finally, at end-diastole, LA acts as a muscular pump contributing to LV filling with active atrial contraction. (LASs: left atrial systolic strain; LASa: left atrial diastolic strain; LASRe: early left atrial strain rate; LASRa: late left atrial strain rate).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-04-0312-80040-gf01.jpg"/></fig>
        </p>
        <p>In addition, 30 healthy individuals were analyzed following the same protocol in order to have a reference population for LA mechanics.</p>
        <p>Two experienced observers carried out the measurements in both populations in different times, in order to determine intra- and inter-observer variability. Intra-observer variability was calculated with measurements of the same rater in different moments including random samples of either patients or healthy controls. The same 2D echocardiographic loops of random samples of both patients and healthy controls were used for inter-observer variability.</p>
        <p>All images were digitally stored for offline analysis.</p>
      </sec>
      <sec>
        <title>Definition of AF recurrence</title>
        <p>AF recurrence was defined as presence of AF at any electrocardiogram or during at least 30 seconds in Holter monitoring.</p>
      </sec>
      <sec>
        <title>Statistical analyses</title>
        <p>Descriptive analyses were performed to explore study population characteristics. Categorical variables were reported as frequencies, and continuous variables with normal distribution were reported as mean &#177; SD. Median and interquartile range were used in cases of non-normality. Normal distribution of continuous variables was studied using Kolmogorv-Smirnov test.</p>
        <p>Differences among cohorts were analyzed using Chi-square test for categorical variables (or Fisher&#180;s exact test when the comparison group was &lt; 30 individuals), and Student-<italic>t</italic>-test (or Mann-Whitney test if the comparison group was &lt; 30 and in case of non-normal distribution) for the numerical ones.</p>
        <p>Kaplan-Meier method was used for describing event free survival (AF) over time; the median was used as cutoff value to compare quantitative variables and differences between groups were investigated with the log-rank test. Those variables with p value &lt; 0.15 were included for multivariate analyses using a Cox proportional hazard model.</p>
        <p>Significance was considered with a p value of &lt; 0.05.</p>
        <p>Statistical analyses were performed using SPSS (Statistical Program for the Social Sciences [SPSS Inc., Chicago, USA]) version 15.0.</p>
        <p>Intra- and inter-observer agreements in the speckle-tracking measurements were studied by regression analyses and calculation of the intraclass correlation coefficient. Bland Altman plots, combined with calculation of 95% limits of agreement were also generated. For this analysis MedCalc Statistical Software version 15.6.1 (MedCalc Software bvba, Ostend, Belgium) was employed.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>AF recurrence was identified in 9 out of 53 cases in the immediate post-surgery period (3 months). These 9 patients were excluded for subsequent follow-up.</p>
      <p>The 44 patients with sustained SR after 3 months were included in the echocardiographic and rhythm follow-up. Baseline characteristics of this series are shown in <xref ref-type="table" rid="t1">Table 1</xref>.</p>
      <table-wrap id="t1">
        <label>Table 1</label>
        <caption>
          <title>Baseline characteristics of patients who maintained sinus rhythm in the immediate post-surgery period (3 months) (n = 44)</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="50%"/>
            <col width="50%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">Characteristics</th>
              <th align="center">
							</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Age (years)</td>
              <td align="center">69 &#177; 9</td>
            </tr>
            <tr>
              <td align="left">Female gender, n (%)</td>
              <td align="center">32 (73%)</td>
            </tr>
            <tr>
              <td align="left">Mitral surgery, n (%)</td>
              <td align="center">36 (82%)</td>
            </tr>
            <tr>
              <td align="left">Aortic surgery, n (%)</td>
              <td align="center">16 (37%)</td>
            </tr>
            <tr>
              <td align="left">Tricuspid intervention, n (%)</td>
              <td align="center">13 (29.5%)</td>
            </tr>
            <tr>
              <td align="left">Cryoablation, n (%)</td>
              <td align="center">36 (82%)</td>
            </tr>
            <tr>
              <td align="left">Antiarrhythmic treatment at discharge, n (%)</td>
              <td align="center">13 (29.5%)</td>
            </tr>
            <tr>
              <td align="left">ACE inhibitors at discharge, n (%)</td>
              <td align="center">21 (48%)</td>
            </tr>
            <tr>
              <td align="left">AF duration &gt; 1 year before surgery, n (%)</td>
              <td align="center">26 (59%)</td>
            </tr>
            <tr>
              <td align="left">LA biplane volume (mL/m<sup>2</sup>)</td>
              <td align="center">68 &#177; 22</td>
            </tr>
            <tr>
              <td align="left">AP LA diameter (mm/m<sup>2</sup>)</td>
              <td align="center">28.9 &#177; 5</td>
            </tr>
            <tr>
              <td align="left">LVEF (%)</td>
              <td align="center">63 &#177; 12</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <p>ACE: angiotensin converting enzyme; AF: atrial fibrillation; AP: anteroposterior; LA: left atrium; LVEF: left ventricular ejection fraction.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>The majority of the population underwent mitral surgery (28 patients, 63.6%), 8 (18.2%) mitral and aortic, and only 8 required exclusively aortic intervention. Mitral valve surgery included 34 prosthetic replacement procedures (26 mechanical and 8 biological), and two mitral valve repair surgeries. Valve replacement was the procedure employed in all patients with aortic disease (12 mechanical and 4 biological). There were 13 (29.5%) tricuspid annuloplasties using Carpentier-Edwards ring in all cases.</p>
      <p>Overall, the study population showed preserved left ventricular ejection fraction (LVEF) and severely dilated LA. These patients were predominantly women with a mean age of 69 &#177; 9 years old (y.o.). Treatment at discharge included amiodarone in 30% of patients and angiotensin-converting-enzyme (ACE) inhibitors in 48% of patients.</p>
      <p>After a mean follow up of 17 &#177; 2 months, 13 new post-operative cases of AF were identified.</p>
      <p>Myocardial deformation parameters (strain and strainR) for assessing LA mechanical function after SA were obtained from 1,245 left atrial segments that were correctly analyzed (71% of possible). On average, 15.5% and 19.4% of 24 potential segments were analyzed per patient and per control, respectively. LA mechanical function (strain and strainR) was significantly worse in all patients than in normal population, independently of SR maintenance (<xref ref-type="table" rid="t2">Table 2</xref>, <xref ref-type="fig" rid="f2">Figure 2</xref>).</p>
      <table-wrap id="t2">
        <label>Table 2</label>
        <caption>
          <title>Strain and strain rate parameters in the post-surgery group versus healthy individuals (Median and Interquatile Range were used because non-normal distribution of variables). P values were calculated with Mann-Whitney test</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="20%"/>
            <col width="20%"/>
            <col width="20%"/>
            <col width="20%"/>
            <col width="20%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">
							</th>
              <th align="center">LASs Median (P<sub>25</sub>-P<sub>75</sub>)</th>
              <th align="center">LASa Median (P<sub>25</sub>-P<sub>75</sub>)</th>
              <th align="center">LASRe Median (P<sub>25</sub>-P<sub>75</sub>)</th>
              <th align="center">LASRa Median (P<sub>25</sub>-P<sub>75</sub>)</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Post-surgery group</td>
              <td align="center">16.9 (14.1-20.6)</td>
              <td align="center">5.9 (4.5-7)</td>
              <td align="center">-0.55 (-0.45- -0.67)</td>
              <td align="center">-0.41 (-0.56- -0.25)</td>
            </tr>
            <tr>
              <td align="left">Control group</td>
              <td align="center">42.5 (36.3-48.8)</td>
              <td align="center">13.1 (11.6-16.2)</td>
              <td align="center">-1.83 (-1.4- -2)</td>
              <td align="center">-1.6 (-1.8- -1.4)</td>
            </tr>
            <tr>
              <td align="left">p</td>
              <td align="center">&lt; 0.001</td>
              <td align="center">&lt; 0.001</td>
              <td align="center">&lt; 0.001</td>
              <td align="center">&lt; 0.001</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN2">
            <p>LASe: LA systolic strain; LASa: LA diastolic strain; LASRe: LA early strain rate; LASRa: LA late strain rate</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>
        <fig id="f2">
          <label>Figure 2</label>
          <caption>
            <title>Intraclass correlation coefficient calculated (ICC) and Bland Altman difference plot combined with calculation of 95% limits of agreement (CI) of the intra-rater (A,C) and inter-rater (B,D) agreement of LA strain (LA S) and LA strain rate (LA SR)</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-110-04-0312-80040-gf02.jpg"/></fig>
      </p>
      <p>As showed in <xref ref-type="fig" rid="f3">Figure 3</xref>, intraclass correlation coefficient was always &gt; 0.80, that represents good to excellent reliability and reproducibility of measurements.<xref ref-type="bibr" rid="B13">13</xref>
			</p>
      <p>
        <fig id="f3">
          <label>Figure 3</label>
          <caption>
            <title>Strain and strain rate curves in a healthy individual (A and B, respectively) and in a post-surgery patient (C and D, respectively).</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-110-04-0312-80040-gf03.jpg"/></fig>
      </p>
      <p>The univariate analyses showed a trend of AF recurrence related to age, mitral surgery, cryoablation and LA biplane volume (<xref ref-type="table" rid="t3">Table 3</xref>). Patients with mitral valve intervention and cryoablation were younger (66.6 &#177; 8.4 vs 73.6 &#177; 9.1 y.o.; p = 0.041). As patients treated with cryoablation were the same as those with mitral intervention, cryoablation was not included in further analyses to avoid collinearity in the multivariate analysis. No association was found between deformation parameters and AF recurrence.</p>
      <table-wrap id="t3">
        <label>Table 3</label>
        <caption>
          <title>Univariate analysis</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">
							</th>
              <th align="center">AF recurrence n = 13</th>
              <th align="center">SR maintenance n = 31</th>
              <th align="center">p (Univariate)</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">LA biplane volume (ml/m<sup>2</sup>)</td>
              <td align="center">76.4 &#177; 25.5</td>
              <td align="center">63.7 &#177; 19.2</td>
              <td align="center">0.059</td>
            </tr>
            <tr>
              <td align="left">Age (years)</td>
              <td align="center">71.5 &#177; 7</td>
              <td align="center">66 &#177; 9</td>
              <td align="center">0.055</td>
            </tr>
            <tr>
              <td align="left">Mitral surgery</td>
              <td align="center">9 (25%)</td>
              <td align="center">27 (75%)</td>
              <td align="center">0.087</td>
            </tr>
            <tr>
              <td align="left">Antiarrhythmic treatment at discharge </td>
              <td align="center">3 (23%)</td>
              <td align="center">10 (77%)</td>
              <td align="center">0.498</td>
            </tr>
            <tr>
              <td align="left">ACE inhibitors at discharge</td>
              <td align="center">6 (28.6%)</td>
              <td align="center">15 (71.4%)</td>
              <td align="center">0.454</td>
            </tr>
            <tr>
              <td align="left">AF duration &gt; 1 year before surgery</td>
              <td align="center">9 (34.6%)</td>
              <td align="center">17 (65.4%)</td>
              <td align="center">0.748</td>
            </tr>
            <tr>
              <td align="left">LASs<xref ref-type="table-fn" rid="TFN4">*</xref>
							</td>
              <td align="center">14.1 (13.1-20.1)</td>
              <td align="center">17.2 (15.4-21.4)</td>
              <td align="center">0.961</td>
            </tr>
            <tr>
              <td align="left">LASa<xref ref-type="table-fn" rid="TFN4">*</xref>
							</td>
              <td align="center">5.6 (3.3-6.3)</td>
              <td align="center">5.9 (4.7-7.4)</td>
              <td align="center">0.385</td>
            </tr>
            <tr>
              <td align="left">LASRe<xref ref-type="table-fn" rid="TFN4">*</xref>
							</td>
              <td align="center">-0.5 (-0.45- -0.67)</td>
              <td align="center">-0.5 (-0.45- -0.67)</td>
              <td align="center">0.965</td>
            </tr>
            <tr>
              <td align="left">LASRa<xref ref-type="table-fn" rid="TFN4">*</xref>
							</td>
              <td align="center">-0.4 (-0.25- -0.59)</td>
              <td align="center">-0.4 (-0.25- -0.58)</td>
              <td align="center">0.961</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN3">
            <p>P values were calculated with the use of the Mann-Whitney or Fisher&#180;s exact tests.</p>
          </fn>
          <fn id="TFN4">
            <label>(*)</label>
            <p>Variables with non-normal distribution (median and intercuartile range [P<sub>25</sub>-P<sub>75</sub>]). ACE: angiotensin converting enzyme; AF: atrial fibrillation; LA: left atrium; LASs: LA systolic strain; LASa: LA diastolic strain; LASRe: early LA strain rate; LASRa: late LA strain rate.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>As can be seen in <xref ref-type="fig" rid="f4">Figure 4</xref>, employing the univariate log rank test, AF recurrence seems to be associated with: larger LA volume (p = 0.030), older age (p = 0.027), and inversely, with mitral valve intervention (p = 0.006).</p>
      <p>
        <fig id="f4">
          <label>Figure 4</label>
          <caption>
            <title>Log-rank test for comparison of Kaplan-Meier curves according to mitral valve surgery (p = 0.006), age &gt; 69 years old (p = 0.027) and left atrial volume &gt; 64 ml/m<sup>2</sup> (p = 0.030). AF: atrial fibrillation; LA: left atrial; y.o.: years old</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-110-04-0312-80040-gf04.jpg"/></fig>
      </p>
      <p>A Cox proportional hazard model was built to explore potential sources of confusion and interactions. After SA of AF, LA volume was the only parameter associated with sustained SR (p = 0.028). Mitral surgery (p = 0.056) and age (p = 0.412) were not significantly associated with SR maintenance in the multivariate analyses.</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>AF is the most common arrhythmia in general population and is even more common in VHD patients. This arrhythmia is cause of symptoms, hospital admissions, adverse events (systemic embolisms, side effects of antiarrhythmic drugs, etc.) and therefore, has a high impact in survival and quality of life. In addition, the presence of AF determines the necessity for antithrombotic therapy, and even the selection of the type of prosthesis.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref>
			</p>
      <p>This study was conducted in patients who would otherwise have been chosen to heart rate control. Due to the scarcity of data about this treatment in &#8220;pure&#8221; VHD series, the current study may provide novel insights in this clinical setting. We found that after 28 months, 50% of VHD patients with initial successful ablation remained in SR.</p>
      <p>Veasey et al.<xref ref-type="bibr" rid="B14">14</xref> reported rates of SR of 74% in paroxysmal AF and 51% in persistent AF; nevertheless, the mean follow-up time was only 6 months, and, 39% of these patients had exclusively coronary artery bypass surgery. Similar results were found by Gaynor et al.<xref ref-type="bibr" rid="B15">15</xref> and Budera et al.;<xref ref-type="bibr" rid="B16">16</xref> 71% of patients had sustained SR after 6 months and 53.2% after one year respectively, but, these series included patients with lone AF surgery and revascularization for ischemic heart disease. Beukema et al.<xref ref-type="bibr" rid="B17">17</xref> reported one of the largest series including 285 patients with structural heart disease, finding that SR was present in 57.1% of patients after 5 years of follow- up; however, this study does not state the rate of patients with VHD.</p>
      <p>The consensus statement of the American Society of Echocardiography and the European Association of Echocardiography suggests that LA mechanics can be assessed after AF to predict the maintenance of sinus rhythm and after percutaneous atrial septal defect repair. In addition, LA mechanics may offer suitable parameters to identify patients at risk for LA regional failure or arrhythmias or to assess LA characteristics in patients with LA dilatation of undetermined cause.<xref ref-type="bibr" rid="B18">18</xref> LA strain has also been used to predict post-operative AF after mitral valve intervention.<xref ref-type="bibr" rid="B19">19</xref> However, there are no previous data describing LA mechanics after concomitant AF surgical ablation in VHD patients or series aiming to obtain the relationship between recurrence and atrial mechanics in this group of patients.</p>
      <p>We speculate that the lack of association of LA strain and strainR parameters with AF postoperative recurrence may be explained by severe atrial dilation with extensive areas of fibrosis before surgery in both responders and non-responders to AF ablative techniques. Very large areas of atrial fibrosis may result in an important decrease in atrial mechanics, as shown by deformation parameters of patients included in this study in comparison with healthy individuals. Comparisons between responders and non-responders to AF are limited by the very low parameters of atrial deformation in all patients, which affects the sensitivity of deformation parameters to predict AF recurrences. However, the more fibrosis, the less likely it is to maintain SR. For illustrating this hypothesis, in <xref ref-type="fig" rid="f5">Figure 5</xref>, we compare the anatomopathological characteristics of a patient with more extensive fibrosis and AF recurrence (<xref ref-type="fig" rid="f5">Figure 5A</xref>) with another in SR during follow-up (<xref ref-type="fig" rid="f5">Figure 5B</xref>). Larger studies and inclusion of LA tissue sampling should be necessary to demonstrate this hypothesis.</p>
      <p>
        <fig id="f5">
          <label>Figure 5</label>
          <caption>
            <title>Masson's Trichrome. Collagen fibers are stained blue. A) AF recurrence 6 days after ablation. Abundant atrial fibrosis (arrow) of perivascular predominance. B) Sinus rhythm maintenance during follow-up. Mild atrial fibrosis (arrow).</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-110-04-0312-80040-gf05.jpg"/></fig>
      </p>
      <p>In accordance with prior reports,<xref ref-type="bibr" rid="B20">20</xref> in the current study, larger LA was associated with AF recurrence, suggesting that patients who could benefit more from this technique are those with LA volume &lt; 64 ml/m<sup>2</sup>. Another novel contribution of the series presented here, is that despite the fact that LA diameter has been traditionally considered one of the major inclusion criteria for candidate selection, only LA volume appears as a predictor of AF recurrence. To the best of our knowledge, the prognostic value of LA biplane volume to predict recurrences after AF cryoablation in VHD patients has not been previously reported and may contribute to better selection of candidates with VHD.</p>
      <p>The suppression of AF was most successful in patients undergoing mitral valve surgery, patients in whom cryoablation was systematically used. Patients who underwent aortic valve surgery and AF ablation with HIFU-Epicor had significantly lower rate of SR maintenance. In prior publications, the success rate of Epicor system was also lower.<xref ref-type="bibr" rid="B21">21</xref> Endocardial approach (used in cryoablation) has shown higher success rates in comparison with the more superficial epicardial approach (HIFU-Epicor). However, according to other authors, this difference may not be due uniquely to the lower efficiency of the ablation system employed, and they speculate whether the underlying heart disease may also influence outcome, because it is well known, that isolated mitral valve surgery (without additional AF ablation) has a significant beneficial effect on spontaneous conversion to SR.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref>
			</p>
      <p>Antiarrhythmic management is important in patients with recurrent AF in the post-operative period in improving results of SA.<xref ref-type="bibr" rid="B4">4</xref> However, in our study, no association was found between antiarrhythmic treatment and SR maintenance. We could not infer from our data whether this finding was due to the small number of patients was discharged with amiodarone, or if amiodarone is not effective for SR maintenance in these patients.</p>
      <p>In the univariate analyses, age was associated with the recurrence of AF, however, this relationship was not observed after multivariate testing. It appears, therefore, that age is a confounding variable, since patients undergoing both mitral valve intervention and cryoablation are significantly younger.</p>
      <p>It is well known that AF is associated with LA myocardial remodeling and ultra-structural changes, including fibrosis and accumulation of extracellular matrix - effects that may predispose to the formation of zones of slow conduction, which promote re-entry.<xref ref-type="bibr" rid="B22">22</xref> ACE-inhibitors are thought to reduce atrial dilatation, dysfunction, and fibrosis, which may reduce the propensity for developing AF.<xref ref-type="bibr" rid="B23">23</xref> In some studies, after catheter ablation, there is a trend towards fewer AF recurrences in patients treated with ACE-inhibitors, however, the efficacy of this treatment in routine clinical practice remains unknown.<xref ref-type="bibr" rid="B24">24</xref> In the present study, ACE-inhibitors were used in a substantial proportion of patients (48%), but they were not found to be effective enough for preventing AF recurrence.</p>
      <p>As it has been demonstrated in previous studies,<xref ref-type="bibr" rid="B25">25</xref> AF surgical ablation is a safe procedure without increasing total surgical time, in comparison with the traditional Cox-Maze procedure, which has an elevated success rate but significantly increases intraoperative time. In our series we have not found major complications related to this technique.</p>
      <sec>
        <title>Limitations of the study</title>
        <p>Despite the systematic use of 24 hour Holter monitoring in the present series, silent AF remains an important issue in the post-operative follow-up of this type of patients. A major limitation of studies about AF treatment is that the burden of arrhythmia cannot be a reliable determinant unless an implantable device is used. It is also difficult to make a proper comparison with other studies in the absence of universal criteria for defining AF recurrences.</p>
        <p>Results on the antiarrhythmic treatment should be interpreted with caution, since treatment with amiodarone (which was not uniformly employed across patients) could affect the success of the AF ablation technique. When antiarrhythmic drugs were forced into the multivariate model, recurrence predictors remained unchanged.</p>
        <p>This study was carried out for a limited time period, with a relatively small sample size and in a single tertiary center. Multicenter studies and larger number of patients will be needed in the future to obtain more evidences about efficacy and safety of this technique in VHD patients.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusions</title>
      <p>Left atrial volume was larger in patients with AF recurrence, and emerges as the main predictor of recurrences improving candidate selection for this therapy; however, no differences were found regarding myocardial deformation parameters. Despite electrical maintenance of SR, left atrium mechanics did not recover after AF ablation performed during VHD surgery.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This study is not associated with any thesis or dissertation work.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Ethics approval and consent to participate</bold>
        </p>
        <p>This study was approved by the Ethics Committee of the La Princesa hospital. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
      </fn>
    </fn-group>
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        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tayebjee</surname>
              <given-names>MH</given-names>
            </name>
            <name>
              <surname>Creta</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Moder</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Hunter</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Earley</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Dhinoja</surname>
              <given-names>MB</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Impact of angiotensin-converting enzyme-inhibitors and angiotensin receptor blockers on long-term outcome of catheter ablation for atrial fibrillation</article-title>
          <source>Europace</source>
          <year>2010</year>
          <volume>12</volume>
          <issue>11</issue>
          <fpage>1537</fpage>
          <lpage>1542</lpage>
          <pub-id pub-id-type="doi">10.1093/europace/euq284</pub-id>
        </element-citation>
      </ref>
      <ref id="B25">
        <label>25</label>
        <mixed-citation>25 Ad N, Suri RM, Gammie JS, Sheng S, O'Brien SM, Henry L. Surgical ablation of atrial fibrillation trends and outcomes in North America. J Thorac Cardiovasc Surg. 2012;144(5):1051-60. doi: 10.1016/j.jtcvs.2012.07.065.</mixed-citation>
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              <surname>Ad</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Suri</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Gammie</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Sheng</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>O'Brien</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Henry</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>Surgical ablation of atrial fibrillation trends and outcomes in North America</article-title>
          <source>J Thorac Cardiovasc Surg</source>
          <year>2012</year>
          <volume>144</volume>
          <issue>5</issue>
          <fpage>1051</fpage>
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        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="s1" 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>Resultados em M&#233;dio Prazo do Tratamento da Fibrila&#231;&#227;o Atrial na Doen&#231;a Valvular Card&#237;aca Avaliados por Ecocardiografia com <italic>Speckle Tracking</italic></article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Lorenzo</surname>
            <given-names>Natalia</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mendez</surname>
            <given-names>Irene</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Taibo</surname>
            <given-names>Mikel</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Martinis</surname>
            <given-names>Gianfranco</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Badia</surname>
            <given-names>Sara</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Reyes</surname>
            <given-names>Guillermo</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Aguilar</surname>
            <given-names>Rio</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff3">
        <label>1</label>
        <institution content-type="original">Hospital Universitario Infanta Cristina, Parla, Madrid - Espanha</institution>
      </aff>
      <aff id="aff4">
        <label>2</label>
        <institution content-type="original">Hospital Universitario de La Princesa, Madrid - Espanha</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Natalia Lorenzo Mu&#241;oz</bold>, Avenida 9 de junio, 2. 28981, Parla, Madrid - Espanha. E-mail: <email>natalialorenzo84@gmail.com</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa, An&#225;lise e interpreta&#231;&#227;o dos dados, An&#225;lise estat&#237;stica e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Lorenzo N, Aguilar R; Obten&#231;&#227;o de dados: Lorenzo N, Mendez I, Taibo M, Martinis G, Badia S, Reyes G, Aguilar R; Reda&#231;&#227;o do manuscrito: Lorenzo N.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>A fibrila&#231;&#227;o atrial frequentemente afeta pacientes com doen&#231;as das valvas card&#237;acas. A abla&#231;&#227;o da fibrila&#231;&#227;o atrial durante a cirurgia das v&#225;lvulas &#233; uma alternativa para restaurar o ritmo sinusal.</p>
        </sec>
        <sec>
          <title>Objetivos:</title>
          <p>Este estudo teve como objetivos avaliar resultados em m&#233;dio prazo da abla&#231;&#227;o cir&#250;rgica bem sucedida da FA durante cirurgia para doen&#231;a valvar, para explorar a mec&#226;nica do AE ap&#243;s a abla&#231;&#227;o e identificar preditores de recorr&#234;ncia.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Foram inclu&#237;dos 53 candidatos consecutivos. Os crit&#233;rios de elegibilidade para abla&#231;&#227;o foram fibrila&#231;&#227;o atrial persistente &lt;10 anos e di&#226;metro do &#225;trio esquerdo &lt; 6 cm. Tr&#234;s meses ap&#243;s a cirurgia, foram realizados ecocardiografia, Holter por 24 horas, e eletrocardiografias em todos os candidatos que mantiveram o ritmo sinusal (44 pacientes). O estudo eco incluiu par&#226;metros de deforma&#231;&#227;o ao &#225;trio esquerdo (<italic>strain</italic> e taxa de <italic>strain</italic>) usando ecocardiografia bidimensional com <italic>speckle tracking.</italic> Simultaneamente, 30 indiv&#237;duos sadios (controles) foram analisados com o mesmo protocolo para o desempenho do &#225;trio esquerdo. Um valor de P &lt; 0,05 foi considerado significativo.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Ap&#243;s um per&#237;odo m&#233;dio de acompanhamento de 17 &#177; 2 meses, 13 novos casos de fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio foram identificados. Um total de 1245 segmentos do &#225;trio esquerdo foi analisado. O grupo p&#243;s-cir&#250;rgico apresentou dilata&#231;&#227;o grave do &#225;trio esquerdo, e as propriedades mec&#226;nicas do &#225;trio esquerdo n&#227;o se recuperaram ap&#243;s a cirurgia quando comparadas com valores normais. O volume do &#225;trio esquerdo (&#8805; 64 mL/m<sup>2</sup>) foi o &#250;nico preditor independente de recorr&#234;ncia de fibrila&#231;&#227;o atrial (p = 0,03).</p>
        </sec>
        <sec>
          <title>Conclus&#245;es:</title>
          <p>O volume do &#225;trio esquerdo foi maior nos pacientes com fibrila&#231;&#227;o atrial recorrente, e desponta como o principal preditor de recorr&#234;ncia, melhorando, assim, a sele&#231;&#227;o de candidatos para essa terapia. No entanto, n&#227;o foram encontradas diferen&#231;as em rela&#231;&#227;o aos par&#226;metros de deforma&#231;&#227;o do mioc&#225;rdio. Apesar da manuten&#231;&#227;o el&#233;trica do ritmo sinusal, a fun&#231;&#227;o mec&#226;nica do &#225;trio esquerdo n&#227;o se recuperou ap&#243;s a abla&#231;&#227;o da fibrila&#231;&#227;o atrial realizada durante a cirurgia para doen&#231;a da valva card&#237;aca.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>T&#233;cnicas de Abl&#231;&#227;o</kwd>
        <kwd>Fibrila&#231;&#227;o Atrial</kwd>
        <kwd>Doen&#231;as das Valvas Card&#237;acas</kwd>
        <kwd>Crioabla&#231;&#227;o</kwd>
        <kwd>Ecocardiografia</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A fibrila&#231;&#227;o atrial (FA) &#233; um problema s&#233;rio e frequente na doen&#231;a valvar card&#237;aca (DVC), afetando mais de 30% desses pacientes. A DVC leva &#224; sobrecarga de press&#227;o e/ou volume dos &#225;trios, especialmente no &#225;trio esquerdo (AE) em doen&#231;a card&#237;aca esquerda. A FA est&#225; associada &#224; maior morbidade e mortalidade na popula&#231;&#227;o geral, e principalmente nos pacientes com DVC, os quais demandam um limiar mais baixo de anticoagula&#231;&#227;o devido ao maior risco de tromboembolismo. A FA tamb&#233;m afeta a tomada de decis&#227;o na escolha do tipo de pr&#243;tese.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref>
				</p>
        <p>A abla&#231;&#227;o da FA durante a cirurgia card&#237;aca foi demonstrada como um procedimento seguro e efetivo na restaura&#231;&#227;o do ritmo sinusal (RS). Apesar de o procedimento Cox-Maze original haver sido descrito em pacientes com FA somente, seu uso foi estendido a pacientes com doen&#231;a org&#226;nica associada.<xref ref-type="bibr" rid="B3">3</xref> De acordo com alguns autores, a taxa de sucesso do procedimento pode exceder 80%. No entanto, existem poucos dados sobre resultados dessa t&#233;cnica em pacientes com doen&#231;a valvar com FA persistente.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref>
				</p>
        <p>O <italic>strain</italic> mioc&#225;rdico e taxa de <italic>strain</italic> (strainR) representam a magnitude e a taxa da deforma&#231;&#227;o mioc&#225;rdica, respectivamente. A obten&#231;&#227;o do <italic>strain</italic> atrial e da strainR por imagem de Doppler tecidual (DT) ou por ecocardiografia bidimensional com a t&#233;cnica de <italic>speckle tracking</italic> s&#227;o t&#233;cnicas fact&#237;veis e reprodut&#237;veis para avaliar a mec&#226;nica do AE.<xref ref-type="bibr" rid="B6">6</xref>
				</p>
        <p>Este estudo teve como objetivos avaliar resultados em m&#233;dio prazo da abla&#231;&#227;o cir&#250;rgica bem sucedida da FA em pacientes com DVC, explorar a mec&#226;nica do AE utilizando imagens de ultrassom e da strainR ap&#243;s AC da FA durante tratamento cir&#250;rgico da DVC, e identificar preditores cl&#237;nicos e ecocardiogr&#225;ficos da recorr&#234;ncia durante o acompanhamento.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <sec>
          <title>Elegibilidade dos pacientes</title>
          <p>N&#243;s inclu&#237;mos, prospectivamente, candidatos &#224; abla&#231;&#227;o cir&#250;rgica, que foram submetidos &#224; cirurgia da v&#225;lvula card&#237;aca entre maio de 2008 e maio de 2012 em nossa institui&#231;&#227;o.</p>
          <p>Os crit&#233;rios de elegibilidade para a cirurgia de FA inclu&#237;ram FA persistente com menos de 10 anos de progress&#227;o e di&#226;metro do &#225;trio esquerdo (AE) e di&#226;metro &#226;ntero-posterior menor que 6 cm no eixo longo do ecocardiograma transtor&#225;cico pr&#233;-operat&#243;rio.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref> Todos os candidatos foram informados e assinaram o termo de consentimento para a realiza&#231;&#227;o do procedimento, de acordo com o comit&#234; de &#233;tica local.</p>
          <p>Cinquenta e tr&#234;s candidatos submetidos &#224; cirurgia da v&#225;lvula card&#237;aca foram inclu&#237;dos para a abla&#231;&#227;o cir&#250;rgica.</p>
          <p>O sucesso do procedimento de abla&#231;&#227;o da FA foi considerado quando os pacientes apresentavam RS preservado na alta hospitalar. Todos esses pacientes foram selecionados para o acompanhamento inicial. Ap&#243;s a estabiliza&#231;&#227;o do ritmo, que ocorre pelo menos 3 meses ap&#243;s a cirurgia,<xref ref-type="bibr" rid="B8">8</xref> era marcado o exame de ecocardiograma, e foram realizados eletrocardiogramas e monitora&#231;&#227;o ambulatorial em 24 horas (Holter) regulares em todos os candidatos que permaneciam em RS (44 pacientes). A monitoriza&#231;&#227;o de Holter foi programada um m&#234;s ap&#243;s o estudo ecocardiogr&#225;fico, e os exames de eletrocardiografia foram realizados durante as visitas cl&#237;nicas (no m&#237;nimo duas visitas durante o primeiro ano de seguimento). Pacientes com FA persistente durante os primeiros 3 meses ap&#243;s a cirurgia foram exclu&#237;dos.</p>
        </sec>
        <sec>
          <title>T&#233;cnica cir&#250;rgica</title>
          <p>Todos os procedimentos foram realizados por esternotomia total e circula&#231;&#227;o extracorp&#243;rea.</p>
          <p>A t&#233;cnica cir&#250;rgica para crioabla&#231;&#227;o foi realizada conforme descrito anteriormente.<xref ref-type="bibr" rid="B9">9</xref> Ap&#243;s a clampagem a&#243;rtica, o AE era aberto quando necess&#225;rio, e o ap&#234;ndice atrial esquerdo era suturado em seu interior com monofilamento 3.0. O sonda de crioabla&#231;&#227;o foi posicionado por 60 segundos &#224; temperatura entre -100&#186;C e -160&#186;C. As linhas foram criadas ao redor das veias pulmonares e ligando esses c&#237;rculos. Tr&#234;s linhas adicionais foram feitas: entre as veias pulmonares esquerdas e a ap&#234;ndice esquerdo, entre as veias pulmonares esquerdas e a por&#231;&#227;o P3 do anel mitral, e entre a v&#225;lvula tric&#250;spide e a veia cava inferior.</p>
          <p>Nos casos em que a atriotomia esquerda n&#227;o era necess&#225;ria (em interven&#231;&#245;es a&#243;rticas isoladas), a abla&#231;&#227;o card&#237;aca foi realizada por ultrassom focalizado de alta intensidade (HIFU, <italic>high-intensity-focused-ultrasound</italic>, Epicor). O sistema de abla&#231;&#227;o card&#237;aca Epicor (St Jude) &#233; desenhado para realizar HIFU por abordagem exclusivamente epic&#225;rdica, e consiste em uma gama de transdutores posicionados ap&#243;s o dimensionamento adequado ao redor da parede do AE dos orif&#237;cios da veia pulmonar.<xref ref-type="bibr" rid="B4">4</xref>
					</p>
        </sec>
        <sec>
          <title>Estudo ecocardiogr&#225;fico</title>
          <p>Um sistema de ultrassom Vivid 7 Dimension (GE Healthcare) foi usado para o exame ecocardiogr&#225;fico transtor&#225;cico. Todas as imagens e medidas foram adquiridas com um transdutor matricial MS4 seguindo os padr&#245;es estabelecidos pela <italic>European Association of Echocardiography</italic> e a <italic>American Society of Echocardiography</italic>.<xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref>
					</p>
          <p>Os par&#226;metros de deforma&#231;&#227;o foram obtidos durante a s&#237;stole (<italic>strain</italic> sist&#243;lico do &#225;trio esquerdo - SSAE) e a di&#225;stole ventricular (<italic>strain</italic> diast&#243;lico do &#225;trio esquerdo - SDAE), e os par&#226;metros de strainR foram obtidos durante di&#225;stole ventricular inicial e tardia (<xref ref-type="fig" rid="f6">Figura 1</xref>) em 2 planos padr&#245;es (plano apical de 4 e de 2 c&#226;maras), por ecocardiografia <italic>speckle tracking</italic> para evitar a depend&#234;ncia do &#226;ngulo da t&#233;cnica do DT.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>
					</p>
          <p>
            <fig id="f6">
              <label>Figura 1</label>
              <caption>
                <title>Fun&#231;&#245;es f&#225;sicas do &#225;trio esquerdo (AE) e sua rela&#231;&#227;o com o ciclo card&#237;aco. S&#227;o apresentadas as curvas de deforma&#231;&#227;o (strain) e da taxa de strain. Durante a s&#237;stole do ventr&#237;culo esquerdo (VE) e relaxamento isovolum&#233;trico, o AE funciona como um &#8220;reservat&#243;rio&#8221; que se distende na acomoda&#231;&#227;o do fluxo de sangue proveniente das veias pulmonares. Durante a di&#225;stole do VE, o AE comporta-se como um &#8220;condutor&#8221; que se inicia com a abertura da v&#225;lvula mitral e termina antes da contra&#231;&#227;o do AE, permitindo o esvaziamento passivo durante a di&#225;stole e di&#225;stase inicial ventricular. Finalmente, da di&#225;stole final, o AE atua como uma bomba muscular contribuindo para o enchimento do VE por meio da contra&#231;&#227;o atrial ativa. SSAE: strain sist&#243;lico do &#225;trio esquerdo; SDAE: strain diast&#243;lico do &#225;trio esquerdo - SDAE; strainRi: taxa de strain inicial do &#225;trio esquerdo; strainRt: taxa de strain tardio do &#225;trio esquerdo.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-110-04-0312-80040-gf01-pt.jpg"/></fig>
          </p>
          <p>Al&#233;m disso, 30 indiv&#237;duos sadios foram analisados seguindo-se o mesmo protocolo para obtermos uma popula&#231;&#227;o de refer&#234;ncia para a mec&#226;nica do AE.</p>
          <p>Dois observadores experientes conduziram todas as medidas em ambas as popula&#231;&#245;es em tempos diferentes, para determina&#231;&#227;o da variabilidade intraobservadores e entre observadores. A variabilidade intraobservador foi calculada com medidas do mesmo observador em diferentes momentos, incluindo amostras aleat&#243;rias de pacientes e de controles sadios. As mesmas sequ&#234;ncias da ecocardiografia bidimensional das amostras aleat&#243;rias de pacientes e de controles foram usadas para a variabilidade entre observadores.</p>
          <p>Todas as imagens foram armazenadas digitalmente para an&#225;lise <italic>off-line</italic>.</p>
        </sec>
        <sec>
          <title>Defini&#231;&#227;o da recorr&#234;ncia de FA</title>
          <p>A recorr&#234;ncia da FA foi definida como a presen&#231;a de FA em qualquer eletrocardiograma ou durante um m&#237;nimo de 30 segundos de monitoramento por Holter.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>Foram realizadas an&#225;lises descritivas para avaliar as caracter&#237;sticas da popula&#231;&#227;o do estudo. As vari&#225;veis categ&#243;ricas foram descritas em frequ&#234;ncias, e as vari&#225;veis cont&#237;nuas com distribui&#231;&#227;o normal foram descritas em m&#233;dia &#177; DP. Mediana e intervalo interquartil foram usados em casos de n&#227;o normalidade. A distribui&#231;&#227;o normal das vari&#225;veis cont&#237;nuas foi examinada pelo teste Kolmogorv-Smirnov.</p>
          <p>Diferen&#231;as das vari&#225;veis categ&#243;ricas entre as coortes foram analisadas pelo teste do qui-quadrado (ou pelo teste exato de Fisher para compara&#231;&#245;es de grupos com menos de 30 indiv&#237;duos) e o teste <italic>t</italic> de Student (ou teste de Mann-Whitney para compara&#231;&#245;es de grupos com menos de 30 indiv&#237;duos sem distribui&#231;&#227;o normal) foi usado para vari&#225;veis num&#233;ricas.</p>
          <p>O m&#233;todo de Kaplan-Meier foi usado para descrever a sobrevida livre de eventos (FA) ao longo do tempo; a mediana foi usada como ponto de corte para comparar as vari&#225;veis quantitativas, e as diferen&#231;as entre os grupos foram investigadas pelo teste log-rank. Vari&#225;veis com p-valor &lt; 0,15 foram inclu&#237;das para an&#225;lises multivariadas utilizando um modelo de risco proporcional de Cox. Um valor de p &lt; 0,05 foi considerado significativo.</p>
          <p>As an&#225;lises foram realizadas usando o programa SPSS (<italic>Statistical Program for the Social Sciences</italic> [SPSS Inc., Chicago, EUA]).</p>
          <p>Concord&#226;ncias intraobservadores e entre observadores nas medidas do <italic>speckle-trecking</italic> foram estudadas por an&#225;lises de regress&#227;o e c&#225;lculo do coeficiente de correla&#231;&#227;o intraclasse. Foram gerados ainda gr&#225;ficos de Balnd Altman, combinados com o c&#225;lculo de limites de 95% de concord&#226;ncia. Para essa an&#225;lise, foi usado o programa estat&#237;stico MedCalc (MedCalc Software bvba, Oostend, B&#233;lgica) vers&#227;o 15.6.1.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>A recorr&#234;ncia de FA foi identificada em 9 de 53 casos no per&#237;odo p&#243;s-operat&#243;rio imediato (3 meses). Esses pacientes foram exclu&#237;dos do seguimento.</p>
        <p>Os 44 pacientes com RS preservado ap&#243;s 3 meses foram inclu&#237;dos para acompanhamento ecocardiogr&#225;fico e do RS. As caracter&#237;sticas basais dessas s&#233;ries s&#227;o apresentadas na<xref ref-type="table" rid="t4">Tabela 1</xref>.</p>
        <table-wrap id="t4">
          <label>Tabela 1</label>
          <caption>
            <title>Caracter&#237;sticas basais dos pacientes que apresentavam ritmo sinusal preservado no p&#243;s-operat&#243;rio imediato (3 meses) (n = 44)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="50%"/>
              <col width="50%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Caracter&#237;sticas</th>
                <th align="center">
								</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Idade (anos)</td>
                <td align="center">69 &#177; 9</td>
              </tr>
              <tr>
                <td align="left">Sexo feminino, n (%)</td>
                <td align="center">32 (73%)</td>
              </tr>
              <tr>
                <td align="left">Cirurgia mitral, n (%)</td>
                <td align="center">36 (82%)</td>
              </tr>
              <tr>
                <td align="left">Cirurgia a&#243;rtica, n (%)</td>
                <td align="center">16 (37%)</td>
              </tr>
              <tr>
                <td align="left">Interven&#231;&#227;o na v&#225;lvula tric&#250;spide, n (%)</td>
                <td align="center">13 (29.5%)</td>
              </tr>
              <tr>
                <td align="left">Crioabla&#231;&#227;o, n (%)</td>
                <td align="center">36 (82%)</td>
              </tr>
              <tr>
                <td align="left">Tratamento com antiarr&#237;tmicos na alta, n (%)</td>
                <td align="center">13 (29,5%)</td>
              </tr>
              <tr>
                <td align="left">Inibidores de ECA na alta, n (%)</td>
                <td align="center">21 (48%)</td>
              </tr>
              <tr>
                <td align="left">Dura&#231;&#227;o da FA &gt; 1 ano antes da cirurgia, n (%)</td>
                <td align="center">26 (59%)</td>
              </tr>
              <tr>
                <td align="left">Volume biplanar do AE (mL/m<sup>2</sup>)</td>
                <td align="center">68 &#177; 22</td>
              </tr>
              <tr>
                <td align="left">Di&#226;metro AP AE (mm/m<sup>2</sup>)</td>
                <td align="center">28.9 &#177; 5</td>
              </tr>
              <tr>
                <td align="left">FEVE (%)</td>
                <td align="center">63 &#177; 12</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN5">
              <p>ECA: enzima conversora da angiotensina; FA: fibrila&#231;&#227;o atrial; AP: Anteroposterior; AE: &#225;trio esquerdo; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>A maioria da popula&#231;&#227;o submeteu-se &#224; cirurgia mitral (28 pacientes, 63,6%), 8 pacientes &#224; cirurgia mitral e a&#243;rtica, e somente 8 &#224; interven&#231;&#227;o exclusivamente a&#243;rtica. Entre as cirurgias da v&#225;lvula mitral, foram realizados 34 procedimentos para substitui&#231;&#227;o de pr&#243;teses (26 mec&#226;nicas e 8 biol&#243;gicas), e duas cirurgias de corre&#231;&#227;o de v&#225;lvula mitral. A substitui&#231;&#227;o de v&#225;lvula foi o procedimento realizado em todos os pacientes com doen&#231;a a&#243;rtica (12 mec&#226;nicas e 4 biol&#243;gicas). Houve 13 (29,5%) anuloplastias tric&#250;spides, usando o anel Carpentier-Edwards em todos os casos.</p>
        <p>Em geral, a popula&#231;&#227;o do estudo apresentou fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo (FEVE) preservado e dilata&#231;&#227;o grave do AE. Esses pacientes eram predominantemente mulheres, com idade m&#233;dia de 69 &#177; 9 anos. O tratamento na alta hospitalar incluiu amiodarona em 30% dos casos, e inibidor da enzima de convers&#227;o da angiotensina (ECA) em 48% dos pacientes.</p>
        <p>Ap&#243;s um per&#237;odo m&#233;dio de acompanhamento de 17 &#177; 2 meses, foram identificados 13 novos casos de FA no p&#243;s-operat&#243;rio.</p>
        <p>Os par&#226;metros de deforma&#231;&#227;o do mioc&#225;rdio (<italic>strain</italic> e <italic>strainR</italic>) para avalia&#231;&#227;o da fun&#231;&#227;o mec&#226;nica do AE foram obtidos dos 1245 segmentos do AE corretamente analisados (71%). Em m&#233;dia, 15,5% e 19,4% dos 24 segmentos em potencial foram analisados por paciente e por controle, respectivamente. A fun&#231;&#227;o mec&#226;nica do AE (<italic>strain</italic> e <italic>strainR</italic>) foi significativamente pior em todos os pacientes que na popula&#231;&#227;o normal, independentemente da preserva&#231;&#227;o do RS (<xref ref-type="table" rid="t5">Tabela 2</xref>, <xref ref-type="fig" rid="f7">Figura 2</xref>).</p>
        <table-wrap id="t5">
          <label>Tabela 2</label>
          <caption>
            <title>Par&#226;metros de deforma&#231;&#227;o (strain e taxa de strain) no grupo p&#243;s-cir&#250;rgico versus indiv&#237;duos sadios (mediana e intervalo interquartil, utilizados pela n&#227;o normalidade da distribui&#231;&#227;o das vari&#225;veis). Valores de p foram calculados pelo teste de Mann-Whitney</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
								</th>
                <th align="center">SSAE Mediana (P<sub>25</sub>-P<sub>75</sub>)</th>
                <th align="center">SDAE Mediana (P<sub>25</sub>-P<sub>75</sub>)</th>
                <th align="center">strainRi Mediana (P<sub>25</sub>-P<sub>75</sub>)</th>
                <th align="center">strainRt Mediana (P<sub>25</sub>-P<sub>75</sub>)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Grupo p&#243;s-cir&#250;rgico </td>
                <td align="center">16,9 (14,1-20,6)</td>
                <td align="center">5,9 (4,5-7)</td>
                <td align="center">-0,55 (-0,45- -0,67)</td>
                <td align="center">-0,41 (-0,56- -0,25)</td>
              </tr>
              <tr>
                <td align="left">Grupo controle</td>
                <td align="center">42,5 (36,3-48,8)</td>
                <td align="center">13,1 (11,6-16,2)</td>
                <td align="center">-1,83 (-1,4- -2)</td>
                <td align="center">-1,6 (-1,8- -1,4)</td>
              </tr>
              <tr>
                <td align="left">p</td>
                <td align="center">&lt; 0,001</td>
                <td align="center">&lt; 0,001</td>
                <td align="center">&lt; 0,001</td>
                <td align="center">&lt; 0,001</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN6">
              <p>SSAE: strain sist&#243;lico do &#225;trio esquerdo; SDAE: strain diast&#243;lico do &#225;trio esquerdo; strainRi; taxa de strain inicial; strainRt: taxa de strain tardio.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>
          <fig id="f7">
            <label>Figura 2</label>
            <caption>
              <title>Coeficiente de correla&#231;&#227;o intraclasse (CCI) e gr&#225;fico de Bland Altman combinado com limites de concord&#226;ncia de 95% (IC) da concord&#226;ncia intraobservador (A,C) e entre observadores (B,D) das medidas do strain do AE (SAE) e da taxa de strain do &#225;trio esquerdo (strainR).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-04-0312-80040-gf02-pt.jpg"/></fig>
        </p>
        <p>Conforme mostrado na <xref ref-type="fig" rid="f8">Figura 3</xref>, o coeficiente de correla&#231;&#227;o intraclasse foi sempre superior a 0,80, o que representa uma confiabilidade e uma reprodutibilidade das medidas consideradas de boa a excelente.<xref ref-type="bibr" rid="B13">13</xref>
				</p>
        <p>
          <fig id="f8">
            <label>Figura 3</label>
            <caption>
              <title>Curvas de strain e da taxa de strain em um indiv&#237;duo sadio (A e B, respectivamente) e em um paciente p&#243;s-cir&#250;rgico (C e D, respectivamente).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-04-0312-80040-gf03-pt.jpg"/></fig>
        </p>
        <p>An&#225;lises univariadas mostraram uma tend&#234;ncia de recorr&#234;ncia da FA relacionada &#224; idade, cirurgia mitral crioabla&#231;&#227;o e volume do AE pelo m&#233;todo biplanar (<xref ref-type="table" rid="t6">Tabela 3</xref>). Os pacientes com interven&#231;&#227;o da v&#225;lvula mitral e crioabla&#231;&#227;o eram mais jovens (66,6 &#177; 8,4 vs 73,6 &#177; 9,1 anos; p = 0,041). Uma vez que os pacientes tratados com crioabla&#231;&#227;o eram os mesmos que aqueles tratados com interven&#231;&#227;o mitral, a crioabla&#231;&#227;o n&#227;o foi inclu&#237;da nas an&#225;lises seguintes para evitar colinearidade na an&#225;lise multivariada. N&#227;o foi encontrada associa&#231;&#227;o entre os par&#226;metros de deforma&#231;&#227;o e recorr&#234;ncia de FA.</p>
        <table-wrap id="t6">
          <label>Tabela 3</label>
          <caption>
            <title>An&#225;lise univariada</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
								</th>
                <th align="center">Recorr&#234;ncia de FA n = 13</th>
                <th align="center">Manuten&#231;&#227;o do RS n = 31</th>
                <th align="center">p (An&#225;lise univariada)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Volume do AE pelo m&#233;todo biplanar (mL/m<sup>2</sup>)</td>
                <td align="center">76,4 &#177; 25,5</td>
                <td align="center">63,7 &#177; 19,2</td>
                <td align="center">0,059</td>
              </tr>
              <tr>
                <td align="left">Idade (anos)</td>
                <td align="center">71,5 &#177; 7</td>
                <td align="center">669</td>
                <td align="center">0,055</td>
              </tr>
              <tr>
                <td align="left">Cirurgia mitral</td>
                <td align="center">9 (25%)</td>
                <td align="center">27 (75%)</td>
                <td align="center">0,087</td>
              </tr>
              <tr>
                <td align="left">Tratamento com antiarr&#237;tmico na alta</td>
                <td align="center">3 (23%)</td>
                <td align="center">10 (77%)</td>
                <td align="center">0,498</td>
              </tr>
              <tr>
                <td align="left">Inibidores de ECA na alta</td>
                <td align="center">6 (28,6%)</td>
                <td align="center">15 (71,4%)</td>
                <td align="center">0,454</td>
              </tr>
              <tr>
                <td align="left">Dura&#231;&#227;o da FA &gt;1 ano antes da cirurgia</td>
                <td align="center">9 (34,6%)</td>
                <td align="center">17 (65,4%)</td>
                <td align="center">0,748</td>
              </tr>
              <tr>
                <td align="left">SSAE<xref ref-type="table-fn" rid="TFN8">*</xref>
								</td>
                <td align="center">14,1 (13,1-20,1)</td>
                <td align="center">17,2 (15,4-21,4)</td>
                <td align="center">0,961</td>
              </tr>
              <tr>
                <td align="left">SDAEa<xref ref-type="table-fn" rid="TFN8">*</xref>
								</td>
                <td align="center">5,6 (3,3-6,3)</td>
                <td align="center">5,9 (4,7-7,4)</td>
                <td align="center">0,385</td>
              </tr>
              <tr>
                <td align="left">strainRi<xref ref-type="table-fn" rid="TFN8">*</xref>
								</td>
                <td align="center">-0,5 (-0,45- -0,67)</td>
                <td align="center">-0,5 (-0,45- -0,67)</td>
                <td align="center">0,965</td>
              </tr>
              <tr>
                <td align="left">strainRt<xref ref-type="table-fn" rid="TFN8">*</xref>
								</td>
                <td align="center">-0,4 (-0,25- -0,59)</td>
                <td align="center">-0,4 (-0,25- -0,58)</td>
                <td align="center">0,961</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN7">
              <p>Valores de p calculados usando o teste de Mann-Whitney ou o teste exato de Fisher</p>
            </fn>
            <fn id="TFN8">
              <label>(*)</label>
              <p>Vari&#225;veis com distribui&#231;&#227;o normal (mediana e intervalo interquartil [P<sub>25</sub>-P<sub>75</sub>]). AE: &#225;trio esquerdo; ECA: enzima conversora de angiotensina; FA: fibrila&#231;&#227;o atrial; SSAE: strain sist&#243;lico do &#225;trio esquerdo; SDAE: strain diast&#243;lico do &#225;trio esquerdo; strainRi; taxa de strain inicial; strainRt: taxa de strain tardio.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Como pode ser observado na <xref ref-type="fig" rid="f9">Figura 4</xref>, ao usar o teste de log-rank univariado, a recorr&#234;ncia de FA parece estar associada com maior volume do AE (p = 0,030), idade mais avan&#231;ada (p = 0,027), e inversamente com interven&#231;&#227;o da v&#225;lvula mitral (p = 0,006).</p>
        <p>
          <fig id="f9">
            <label>Figura 4</label>
            <caption>
              <title>Teste de log-rank para compara&#231;&#227;o das curvas de Kaplan-Meier de acordo com: cirurgia da v&#225;lvula mitral (p = 0,006), idade &gt; 69 anos (p = 0,027) e volume do &#225;trio esquerdo &gt; 64 ml/m<sup>2</sup> (p = 0,030).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-04-0312-80040-gf04-pt.jpg"/></fig>
        </p>
        <p>O modelo de risco proporcional de Cox foi constru&#237;do para explorar fontes potenciais de confus&#227;o e intera&#231;&#245;es. Ap&#243;s a abla&#231;&#227;o bem sucedida da FA em pacientes com DVC, o volume do AE foi o &#250;nico par&#226;metro associado com RS preservado (p = 0,028). A cirurgia da v&#225;lvula mitral (p = 0,056) e a idade (p = 0,412) n&#227;o foram significativamente associadas com preserva&#231;&#227;o do RS nas an&#225;lises multivariadas.</p>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>A FA &#233; a arritmia mais comum na popula&#231;&#227;o geral e ainda mais comum nos pacientes com DVC. Essa arritmia &#233; causa de sintomas, interna&#231;&#245;es hospitalares, eventos adversos (embolismos sist&#234;micos, efeitos colaterais dos antiarr&#237;tmicos, etc.) e, portanto, tem um alto impacto na sobrevida e na qualidade de vida. Al&#233;m disso, a presen&#231;a de FA determina a necessidade de terapia antitromb&#243;tica, e mesmo a sele&#231;&#227;o do tipo de pr&#243;tese.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref>
				</p>
        <p>Este estudo foi realizado com pacientes que seriam selecionados para o controle da frequ&#234;ncia card&#237;aca. Dada &#224; escassez de dados sobre esse tratamento em pacientes com DVC isolada, o presente estudo fornece novas informa&#231;&#245;es nesse cen&#225;rio cl&#237;nico. Encontramos que, ap&#243;s 28 meses, 50% dos pacientes com DVC com abla&#231;&#227;o inicial bem sucedida permaneceram em RS.</p>
        <p>Veasey et al.,<xref ref-type="bibr" rid="B14">14</xref> relataram taxas de RS de 74% na FA parox&#237;stica e de 51% na FA persistente. No entanto, o tempo m&#233;dio de acompanhamento foi de 6 meses e, 39% desses pacientes apresentaram somente cirurgia de <italic>by-pass</italic> da art&#233;ria coron&#225;ria. Resultados similares foram encontrados por Gaynor et al.,<xref ref-type="bibr" rid="B15">15</xref> e Budera et al.,<xref ref-type="bibr" rid="B16">16</xref> que relataram que 71% dos pacientes apresentaram RS preservado ap&#243;s 6 meses e 53,2% ap&#243;s um ano, respectivamente, mas essas s&#233;ries inclu&#237;ram pacientes com cirurgia para FA isolada e revasculariza&#231;&#227;o para doen&#231;a card&#237;aca isqu&#234;mica. Beukema et al.,<xref ref-type="bibr" rid="B17">17</xref> analisaram uma das maiores s&#233;ries de pacientes, com 285 pacientes com doen&#231;a card&#237;aca estrutural, e relataram que o RS estava presente em 57,1% dos pacientes ap&#243;s 5 anos de acompanhamento; contudo, esse estudo n&#227;o menciona a taxa de pacientes com DVC.</p>
        <p>O consenso da <italic>American Society of Echocardiography</italic> e da <italic>European Association of Echocardiography</italic> sugere que a fun&#231;&#227;o mec&#226;nica do AE pode ser avaliada ap&#243;s a FA para predizer a preserva&#231;&#227;o do SR e ap&#243;s o reparo percut&#226;neo do defeito do septo atrial. Ainda, a mec&#226;nica do AE pode oferecer par&#226;metros adequados para identificar pacientes em risco de insufici&#234;ncia regional do AE ou arritmias, e para avaliar caracter&#237;sticas do AE em pacientes com dilata&#231;&#227;o do AE de causa indeterminada.<xref ref-type="bibr" rid="B18">18</xref> O <italic>strain</italic> do AE tamb&#233;m foi usado para predizer FA p&#243;s-operat&#243;ria ap&#243;s interven&#231;&#227;o na v&#225;lvula mitral.<xref ref-type="bibr" rid="B19">19</xref> No entanto, n&#227;o h&#225; dados pr&#233;vios descrevendo a mec&#226;nica do AE ap&#243;s abla&#231;&#227;o do AE concomitante em pacientes com DVC ou s&#233;rie de DVC ou s&#233;ries, objetivando obter a rela&#231;&#227;o entre recorr&#234;ncia e mec&#226;nica atrial neste grupo de pacientes.</p>
        <p>N&#243;s especulamos que a aus&#234;ncia de associa&#231;&#227;o entre par&#226;metros do <italic>strain</italic> e da <italic>strainR</italic> do AE e recorr&#234;ncia de FA no p&#243;s-operat&#243;rio possa ser explicada pela dilata&#231;&#227;o grave do &#225;trio com extensas &#225;reas de fibrose presentes antes da cirurgia tanto em pacientes que responderam como naqueles que n&#227;o responderam a t&#233;cnicas de abla&#231;&#227;o do AE. &#193;reas muito extensas de fibrose atrial podem resultar em uma diminui&#231;&#227;o importante na fun&#231;&#227;o mec&#226;nica atrial, conforme demonstrado pelos par&#226;metros de deforma&#231;&#227;o dos pacientes inclu&#237;dos neste estudo em compara&#231;&#227;o com indiv&#237;duos sadios. Compara&#231;&#245;es entre pacientes que responderam e aqueles que n&#227;o responderam &#224; FA s&#227;o limitadas pelos par&#226;metros muito baixos de deforma&#231;&#227;o atrial em todos os pacientes, o que afeta a sensibilidade de os par&#226;metros de deforma&#231;&#227;o em predizer FA recorrente. Contudo, quanto maior a fibrose, menor a probabilidade de se manter o RS. Para ilustrar essa hip&#243;tese, na <xref ref-type="fig" rid="f10">Figura 5</xref>, comparamos as caracter&#237;sticas anatomopatol&#243;gicas de um paciente com fibrose mais extensa e FA recorrente (<xref ref-type="fig" rid="f10">Figura 5A</xref>) com outro paciente em RS durante o acompanhamento (<xref ref-type="fig" rid="f10">Figura 5B</xref>). Estudos maiores e inclus&#227;o de amostras teciduais do AE s&#227;o necess&#225;rios para demonstrar essa hip&#243;tese.</p>
        <p>
          <fig id="f10">
            <label>Figura 5</label>
            <caption>
              <title>Colora&#231;&#227;o tricromo de Masson. Fibras de col&#225;geno est&#227;o coradas de azul. A) recorr&#234;ncia de FA 6 dias ap&#243;s abla&#231;&#227;o. Fibrose atrial abundante (seta) de predomin&#226;ncia perivascular. B) Preserva&#231;&#227;o do ritmo sinusal durante o seguimento. Fibrose atrial leve (seta).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-04-0312-80040-gf05-pt.jpg"/></fig>
        </p>
        <p>Em concord&#226;ncia com estudos pr&#233;vios,<xref ref-type="bibr" rid="B20">20</xref> no presente estudo, AE maior foi associado com FA recorrente, sugerindo que os pacientes que mais se beneficiariam dessa t&#233;cnica s&#227;o aqueles com volume atrial esquerdo &lt; 64 mL/m<sup>2</sup>. Outra nova contribui&#231;&#227;o das s&#233;ries aqui apresentadas &#233; o fato de que, apesar de o di&#226;metro do AE ser tradicionalmente considerado um dos principais crit&#233;rios de inclus&#227;o para a sele&#231;&#227;o dos candidatos, somente o volume do AE parece ser um preditor de recorr&#234;ncia de FA. Em nosso conhecimento, o valor progn&#243;stico volume do AE pelo m&#233;todo biplanar em predizer recorr&#234;ncias ap&#243;s a crioabla&#231;&#227;o da FA em pacientes com DVC ainda n&#227;o relatado, e pode contribuir para uma melhor sele&#231;&#227;o dos candidatos com DVC.</p>
        <p>A supress&#227;o da FA foi mais bem sucedida em pacientes submetidos &#224; cirurgia da valva mitral, nos quais a crioabla&#231;&#227;o foi usada sistematicamente. Pacientes que se submeteram &#224; cirurgia da valva a&#243;rtica e abla&#231;&#227;o da FA com HIFU-Epicor tiveram taxas significativamente mais baixas de preserva&#231;&#227;o do RS. Em publica&#231;&#245;es anteriores, a taxa de sucesso do sistema Epicor tamb&#233;m foi mais baixa.<xref ref-type="bibr" rid="B21">21</xref> A abordagem endocard&#237;aca (usada na crioabla&#231;&#227;o) mostrou taxas de sucesso mais altas em compara&#231;&#227;o &#224; abordagem mais superficial no epic&#225;rdio (HIFU-Epicor). Entretanto, de acordo com outros autores, essa diferen&#231;a pode n&#227;o ser unicamente devido &#224; menor efic&#225;cia do sistema de abla&#231;&#227;o empregado, e eles especulam que a doen&#231;a card&#237;aca de base possa tamb&#233;m influenciar o desfecho, j&#225; que se sabe que a cirurgia isolada da v&#225;lvula mitral (sem abla&#231;&#227;o da FA) tem um efeito ben&#233;fico significativo sobre a convers&#227;o espont&#226;nea para o RS.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref>
				</p>
        <p>O manejo com antiarr&#237;tmicos &#233; importante nesses pacientes com FA recorrente no per&#237;odo p&#243;s-operat&#243;rio para melhorar os resultados da abla&#231;&#227;o bem sucedida.<xref ref-type="bibr" rid="B4">4</xref> No entanto, em nosso estudo, n&#227;o foi encontrada associa&#231;&#227;o entre tratamento com antiarr&#237;tmicos e a manuten&#231;&#227;o do RS.</p>
        <p>Na an&#225;lise univariada, a idade foi associada com recorr&#234;ncia de FA, no entanto, essa rela&#231;&#227;o n&#227;o foi observada ap&#243;s an&#225;lise multivariada. Parece, portanto, que a idade &#233; uma vari&#225;vel de confus&#227;o, j&#225; que os pacientes submetidos tanto &#224; interven&#231;&#227;o na v&#225;lvula mitral como &#224; crioabla&#231;&#227;o s&#227;o significativamente mais jovens.</p>
        <p>Sabe-se que a FA est&#225; associada com remodela&#231;&#227;o mioc&#225;rdica no AE e mudan&#231;as ultraestruturais, incluindo fibrose e ac&#250;mulo de matriz extracelular - efeitos que podem predispor &#224; forma&#231;&#227;o de zonas de condu&#231;&#227;o lenta, que promovem a reentrada.<xref ref-type="bibr" rid="B22">22</xref> Acredita-se que inibidores de ECA reduzam a dilata&#231;&#227;o, disfun&#231;&#227;o e fibrose atrial, o que pode diminuir a probabilidade de se desenvolver FA.<xref ref-type="bibr" rid="B23">23</xref> Em alguns estudos, ap&#243;s a abla&#231;&#227;o por cateter, h&#225; uma tend&#234;ncia a menor recorr&#234;ncia de FA em pacientes tratados com inibidores de ECA; no entanto, a efic&#225;cia desse tratamento na pr&#225;tica cl&#237;nica de rotina ainda &#233; desconhecida.<xref ref-type="bibr" rid="B24">24</xref> No presente estudo, apesar de os inibidores de ECA terem sido usados em uma propor&#231;&#227;o importante dos pacientes (48%), n&#227;o foram eficazes o suficiente para prevenir a recorr&#234;ncia de FA.</p>
        <p>Conforme foi demonstrado em estudos pr&#233;vios,<xref ref-type="bibr" rid="B25">25</xref> a abla&#231;&#227;o cir&#250;rgica da FA &#233; um procedimento seguro, e que n&#227;o promove aumento no tempo de cirurgia em compara&#231;&#227;o ao procedimento tradicional de Cox-Maze, o qual apresenta uma elevada taxa de sucesso, mas aumenta significativamente o tempo intraoperat&#243;rio. Em nossas s&#233;ries, n&#227;o encontramos complica&#231;&#245;es importantes relacionadas a essa t&#233;cnica.</p>
        <sec>
          <title>Limita&#231;&#245;es do estudo</title>
          <p>Apesar do uso sistem&#225;tico do Holter 24 horas nas s&#233;ries do presente estudo, a FA silenciosa permanece uma importante quest&#227;o no acompanhamento no p&#243;s-operat&#243;rio desse grupo de pacientes. Uma importante limita&#231;&#227;o dos estudos sobre tratamento de FA &#233; o fato de que o peso da arritmia n&#227;o poder ser considerado um determinante confi&#225;vel ao menos que um dispositivo implant&#225;vel seja usado. Tamb&#233;m &#233; dif&#237;cil fazer compara&#231;&#245;es adequadas com outros estudos na aus&#234;ncia de crit&#233;rios universalmente definidos para definir recorr&#234;ncia de FA.</p>
          <p>Os resultados do tratamento com antiarr&#237;tmicos devem ser interpretados com cautela, uma vez que o tratamento com amiodarona (que n&#227;o foi uniformemente usado em todos os pacientes) pode afetar o sucesso da t&#233;cnica de abla&#231;&#227;o da FA. Quando as drogas antiarr&#237;tmicas foram introduzidas no modelo multivariado, os preditores de recorr&#234;ncia permaneceram inalterados.</p>
          <p>Este estudo foi realizado durante um per&#237;odo limitado de tempo, com uma amostra relativamente pequena e em um &#250;nico centro terci&#225;rio. Estudos multic&#234;ntricos com um maior numero de pacientes ser&#227;o necess&#225;rios no futuro para obter maiores evid&#234;ncias sobre a efic&#225;cia e a seguran&#231;a dessa t&#233;cnica em pacientes com DVC.</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#245;es</title>
        <p>O volume do AE foi maior nos pacientes com FA recorrente, e desponta como o preditor principal de recorr&#234;ncias, melhorando a sele&#231;&#227;o de candidatos para essa terapia. No entanto, n&#227;o foram encontradas diferen&#231;as nos par&#226;metros de deforma&#231;&#227;o mioc&#225;rdica. Apesar da manuten&#231;&#227;o el&#233;trica do RS, a mec&#226;nica do AE n&#227;o foi recuperada ap&#243;s a abla&#231;&#227;o da FA realizada durante a cirurgia para DVC.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Aprova&#231;&#227;o &#233;tica e consentimento informado</bold>
          </p>
          <p>Este estudo foi aprovado pelo Comit&#234; de &#201;tica da La Princesa Hospital. Todos os procedimentos envolvidos nesse estudo est&#227;o de acordo com a Declara&#231;&#227;o de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes inclu&#237;dos no estudo.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
