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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.0" specific-use="sps-1.3" xml:lang="en">
  <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">m7tfQY45Xc7rT44c3ShLTHw</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2016000400289</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2016005007101</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20160028</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Risk Prediction of Cardiovascular Complications in Pregnant Women With Heart Disease</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Martins</surname>
            <given-names>Luciana Carvalho</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Freire</surname>
            <given-names>Claudia Maria Vilas</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Capuru&#231;u</surname>
            <given-names>Carolina Andrade Bragan&#231;a</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nunes</surname>
            <given-names>Maria do Carmo Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rezende</surname>
            <given-names>Cezar Alencar de Lima</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Universidade Federal de Minas Gerais</institution>
        <addr-line>
          <named-content content-type="city">Belo Horizonte</named-content>
          <named-content content-type="state">MG</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Federal de Minas Gerais - UFMG, Belo Horizonte, MG - Brazil</institution>
        <institution content-type="normalized">Universidade Federal de Minas Gerais</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Funda&#231;&#227;o Hospitalar do Estado de Minas Gerais</institution>
        <institution content-type="orgdiv1">Maternidade Odete Valadares</institution>
        <addr-line>
          <named-content content-type="city">Belo Horizonte</named-content>
          <named-content content-type="state">MG</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Maternidade Odete Valadares - Funda&#231;&#227;o Hospitalar do Estado de Minas Gerais, Belo Horizonte, MG - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Claudia Maria Vilas Freire</bold>, Universidade Federal de Minas Gerais &#8211; UFMG. Rua Ivai 96, Serra. Postal Code 30210-520, Belo Horizonte, MG &#8211; Brazil. E-mail: <email>claudiavilasfreire@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Martins LC, Freire CMV, Rezende CAL; Acquisition of data: Martins LC, Freire CMV; Analysis and interpretation of the data: Martins LC, Freire CMV, Capuru&#231;u CAB, Nunes MCP; Statistical analysis: Martins LC, Freire CMV, Capuru&#231;u CAB, Nunes MCP; Writing of the manuscript: Rezende CAL; Critical revision of the manuscript for intellectual content: Martins LC, Freire CMV, Nunes MCP, Rezende CAL.</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>08</day>
        <month>03</month>
        <year>2016</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>04</month>
        <year>2016</year>
      </pub-date>
      <volume>106</volume>
      <issue>04</issue>
      <fpage>289</fpage>
      <lpage>296</lpage>
      <history>
        <date date-type="received">
          <day>30</day>
          <month>03</month>
          <year>2015</year>
        </date>
        <date date-type="rev-recd">
          <day>26</day>
          <month>10</month>
          <year>2015</year>
        </date>
        <date date-type="accepted">
          <day>06</day>
          <month>11</month>
          <year>2015</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0">
          <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>Heart disease in pregnancy is the leading cause of non- obstetric maternal death. Few Brazilian studies have assessed the impact of heart disease during pregnancy.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To determine the risk factors associated with cardiovascular and neonatal complications.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>We evaluated 132 pregnant women with heart disease at a High-Risk Pregnancy outpatient clinic, from January 2005 to July 2010. Variables that could influence the maternal-fetal outcome were selected: age, parity, smoking, etiology and severity of the disease, previous cardiac complications, cyanosis, New York Heart Association (NYHA) functional class &gt; II, left ventricular dysfunction/obstruction, arrhythmia, drug treatment change, time of prenatal care beginning and number of prenatal visits. The maternal-fetal risk index, Cardiac Disease in Pregnancy (CARPREG), was retrospectively calculated at the beginning of prenatal care, and patients were stratified in its three risk categories.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>Rheumatic heart disease was the most prevalent (62.12%). The most frequent complications were heart failure (11.36%) and arrhythmias (6.82%). Factors associated with cardiovascular complications on multivariate analysis were: drug treatment change (p = 0.009), previous cardiac complications (p = 0.013) and NYHA class III on the first prenatal visit (p = 0.041). The cardiovascular complication rates were 15.22% in CARPREG 0, 16.42% in CARPREG 1, and 42.11% in CARPREG &gt; 1, differing from those estimated by the original index: 5%, 27% and 75%, respectively. This sample had 26.36% of prematurity.</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>The cardiovascular complication risk factors in this population were drug treatment change, previous cardiac complications and NYHA class III at the beginning of prenatal care. The CARPREG index used in this sample composed mainly of patients with rheumatic heart disease overestimated the number of events in pregnant women classified as CARPREG 1 and &gt; 1, and underestimated it in low-risk patients (CARPREG 0).</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Cardiovascular Diseases / complications</kwd>
        <kwd>Pregnant Women</kwd>
        <kwd>Risk Factors</kwd>
        <kwd>Heart Failure</kwd>
        <kwd>Arrhythmias, Cardiac</kwd>
        <kwd>Rheumatic Heart Disease</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Maternal mortality is still very high in Brazil. According to the Brazilian Unified Health System data bank (DATASUS), in 2007 the maternal mortality in Brazil was 77 per 100,000 live births. Heart disease in pregnancy is the first cause of non-obstetric maternal death and the fourth cause of maternal death in general.<xref ref-type="bibr" rid="B1">1</xref> Diagnosing heart disease before or at the beginning of pregnancy is fundamental to assess the maternal-fetal risk, and has an impact on the patients' approach and therapeutic strategy. The other causes of maternal death are inherent to the condition, and, unlike heart disease, are usually unpredictable.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref>
			</p>
      <p>Several studies have investigated the risk factors for adverse outcomes and cardiac complications during pregnancy in women with heart diseases.<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B6">6</xref> However, only a few Brazilian studies have assessed them.<xref ref-type="bibr" rid="B7">7</xref> The present study had the following objectives: to establish the prevalence and etiology of heart diseases in pregnant women cared for at our referral center; to identify the most frequent maternal complications and their repercussions on maternal and perinatal outcomes; and to assess the risk predictors of cardiac complications that may influence maternal-fetal outcomes.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>In addition, this study assessed the maternal Cardiac Disease in Pregnancy (CARPREG) risk score, developed by Siu et al.,<xref ref-type="bibr" rid="B4">4</xref> aiming at classifying the risk of pregnant women with heart disease and at observing the predictors of cardiac and neonatal complications in that population with characteristics different from those of the population studied by the authors of that risk score.</p>
      <p>This study included pregnant women with heart disease followed up from prenatal care up to delivery and puerperium by the team of the High-Risk Pregnancy Care Sector, from January 2005 to July 2010. A total of 153 women were cared for at that sector during that period. This study was approved by the Committee on Ethics in Research, and all patients provided written informed consent.</p>
      <p>All pregnant women were examined by the same cardiologist and underwent tests to confirm the diagnosis and to classify and assess the severity of the heart disease, such as Doppler echocardiography, electrocardiography and 24-hour Holter monitoring.</p>
      <p>To analyze the risk predictors of maternal cardiac complications from this historical cohort, this study included only patients with complete information. Those with the following characteristics were excluded: miscarriage (fetal loss before the 20th week); delivery at other institutions; twin pregnancies; and peripartum cardiomyopathy developed in the puerperium period. Thus, 132 of 153 pregnant women with heart disease followed up at the sector were included.</p>
      <sec>
        <title>Variables assessed</title>
        <p>The possible risk predictors of maternal cardiovascular complications assessed were as follows: age; parity; number of visits to the high-risk prenatal care (HRPC); HRPC beginning on the third trimester; maternal smoking; previous cardiac complications and previous surgical or clinical heart treatments; need to begin or change cardiac medication during pregnancy for patients who changed, at the most, one functional class during follow-up, or dose adjustment to abide by a follow-up protocol; valve prosthesis; New York Heart Association (NYHA) functional class &#8805; III at the beginning of HRPC; left ventricular (LV) systolic dysfunction; associated preeclampsia or systemic arterial hypertension (SAH); left heart obstruction (LHO); and calculated CARPREG risk score. The following disorders were grouped as LHO: mitral stenosis with valve area &lt; 2.0 cm<xref ref-type="bibr" rid="B2">2</xref>; aortic stenosis with valve area &lt; 1.5 cm<xref ref-type="bibr" rid="B2">2</xref>; and LV outflow tract gradient &gt; 30 mm Hg.</p>
        <p>The following variables relating to the ongoing pregnancy were assessed: gestational age at the beginning of prenatal care and number of consultations; cardiac complications during pregnancy; invasive procedures required during prenatal care; NYHA functional classification; comorbidities; delivery type; hospital length of stay; and obstetric complications. The neonatal variables assessed were gestational age at the time of delivery and birth weight.</p>
        <p>The prediction index of risk for complications associated with pregnancy in women with heart disease (CARPREG risk score) was retrospectively calculated for each patient. The variables associated with cardiovascular complications according to the CARPREG risk score are defined in <xref ref-type="table" rid="t4">Chart 1</xref>. Pregnant women are classified as CARPREG 0, 1 or &gt; 1 in the presence of none, one, or more than one defined risk factor.<xref ref-type="bibr" rid="B4">4</xref> The patients in this study were distributed into three groups: CARPREG 0, CARPREG 1 and CARPREG &gt; 1, and the percentage of complications occurring in each group was compared to that predicted according to the original score: 5%, 27% and 75%, respectively.</p>
        <table-wrap id="t4">
          <label>Chart 1</label>
          <caption>
            <title>CARPREG (Cardiac Disease in Pregnancy) risk score. NYHA: New York Heart Association.</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th align="left">
                  <bold>Predictors of cardiovascular events</bold>
                </th>
                <th align="center">
                  <bold>Points</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Prior cardiac event (heart failure, transient ischemic attack, infarction prior to pregnancy) or arrhythmias</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">NYHA functional class at baseline &gt; II or cyanosis</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Left heart obstruction (mitral valve area &lt; 2.0 cm2; aortic valve area &lt; 1.5 cm2; and LV outflow tract gradient &gt; 30 mm Hg)</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Reduced systolic ventricular function (ejection fraction &lt; 40%)</td>
                <td align="center">1</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
      </sec>
      <sec>
        <title>Definition of outcomes</title>
        <p>The cardiac complications were described according to the definitions proposed by Siu et al.<xref ref-type="bibr" rid="B4">4</xref> The following cardiac complications were considered: death due to heart disease; heart failure with acute pulmonary edema (documented on chest X-ray or bilateral pulmonary rales on posterior chest auscultation on physical examination); acute myocardial infarction; sustained symptomatic tachyarrhythmia or bradyarrhythmia requiring treatment; worsening of at least 2 NYHA functional classes as compared to baseline; and need for emergency invasive procedures during pregnancy.</p>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>The Statistical Package for the Social Sciences (SPSS 17, Inc., Chicago, IL, USA) software was used for statistical analysis. The continuous variables were presented as mean &#177; standard deviation, and the categorical ones, as frequency and percentage.</p>
        <p>The variables assessed were compared between the pregnant women with cardiovascular complications in pregnancy and those with favorable outcomes by use of the chi-square test (categorical variables) or non-paired Student <italic>t</italic> test (continuous variables with normal distribution).</p>
        <p>Univariate analysis and multivariate logistic regression were performed to identify the variables associated with cardiovascular complications in pregnancy. The criterion used to select the variables to the multivariate model was clinical relevance or p &lt; 0.20 on univariate analysis. A p value &lt; 0.05 was considered statistically significant.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>The maternal age ranged from 16 to 45 years (mean: 27.59 &#177; 7.17). Regarding the number of gestations, 50 patients (37.88%) were on their first gestation, 38 (28.79%) were on their second gestation, and 44 (33.33%) had at least three gestations [15 (11.36%) were on their fifth pregnancy or more].</p>
      <p>Only 34 patients (25.75%) initiated their HRPC follow-up on the first gestational trimester. Most patients (79; 59.85%) initiated their HRPC follow-up on the second trimester, while 19 patients (14.40%), on the third trimester.</p>
      <p>The major heart disease diagnoses in the study population were: rheumatic heart diseases, 82 patients (62.12%); congenital heart diseases, 18 (13.65%); arrhythmias, 15 (11.36%); and mitral valve prolapse, 6 (4.54%). Cardiomyopathies of different causes and other cardiac diseases added up to 11 patients (8.33%).</p>
      <p>Of the 82 pregnant women with rheumatic heart disease, 19 (23.17%) had valve prosthesis, of whom, 14 (73.68%) had normal functioning prostheses and 5 had residual dysfunction or associated lesion in other valves. The mitral biological prosthesis was the most frequently found (13; 68.42%), followed by mitral mechanical prosthesis (3; 15.79%). Two patients had mitral-aortic mechanical prostheses, and only one had an aortic mechanical prosthesis.</p>
      <p>Of the 18 patients with congenital heart disease, 9 (50%) had a shunt defect (ventricular septal defect; atrial septal defect; atrioventricular septal defect; and patent ductus arteriosus), 50% of which had been surgically repaired before pregnancy. Regarding the LHO, one pregnant woman had a bicuspid aortic valve, and another had coarctation of the aorta and bicuspid aortic valve. None of those lesions was surgically corrected before pregnancy. Diseases of the pulmonary valve (pulmonary valve stenosis or double lesion) added up to 3 patients (16.7%). Regarding cyanotic heart diseases, 3 patients were followed up, 2 of whom had uncorrected Ebstein's anomaly and 1 had corrected tetralogy of Fallot. One patient with severe tricuspid regurgitation was observed.</p>
      <p>Fifteen patients (11.36%) had arrhythmic heart disease, 8 of whom (53.33%) had supraventricular tachyarrhythmias (paroxysmal supraventricular tachycardia, atrial flutter or fibrillation). Four patients (26.67%) had bradyarrhythmia (atrioventricular block and bundle branch blocks), and 3 had other arrhythmias.</p>
      <p>Twenty patients (15.15%) smoked 5 to 40 cigarettes per day (mean of 8.63 &#177; 8.95), of whom 31.5% smoked more than 10 cigarettes per day. Regarding the associated comorbidities, 23 patients (17.42%) had one as follows: type I diabetes, 2 patients; chronic obstructive pulmonary disease/asthma, 11; thyroid diseases, 4; nephropathy, 1; epilepsy, 3; dermatomyositis, 1; and megaesophagus, 1.</p>
      <p>Of 132 pregnancies, 57 (43.18%) had cardiovascular complications prior to the ongoing pregnancy. Cardiac decompensation followed by arrhythmias was the most frequent complication.</p>
      <p>Forty-six patients (34.85%) had LHO, 44 of whom (95.65%) had rheumatic mitral stenosis, with a mean valve area of 1.60 cm<sup>2</sup>, which was considered severe in 11 (25%).</p>
      <p>On the first prenatal visit, only 4 patients (3.3%) were classified as NYHA functional class III, 3 of which (75%) had moderate or severe mitral stenosis associated with moderate mitral regurgitation. One patient had dilated cardiomyopathy.</p>
      <p>At baseline, 2 patients had LV ejection fraction lower than 40%, 18 (13.63%) had it between 40% and 60%, and the remaining had it normal (&#8805; 60%).</p>
      <sec>
        <title>Adverse outcomes</title>
        <p>Cardiovascular complications occurred in 30 (22.72%) pregnant women. Cardiac decompensation, diagnosed as a two-level worsening in NYHA functional class or worsening in patients with functional class III at baseline, was the most frequent complication: 15 cases (11.36%). Cardiac arrhythmias occurred in 9 (6.82%) patients. Four patients (3.03%) required invasive procedures during the pregnancy as follows: one stent implantation in aortic coarctation and 3 percutaneous balloon mitral valvoplasties for severe mitral stenosis. One patient with severe mitral and aortic regurgitation and nephrotic syndrome died suddenly in the post-delivery period (<xref ref-type="table" rid="t1">Table 1</xref>).</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>Distribution of the pregnant women according to the occurrence of cardiovascular complications</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th align="left">
                  <bold>Cardiovascular complications</bold>
                </th>
                <th align="center">
                  <bold>n (%)</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Arrhythmias</td>
                <td align="center">8 (26.67)</td>
              </tr>
              <tr>
                <td align="left">Stroke</td>
                <td align="center">2 (6.67)</td>
              </tr>
              <tr>
                <td align="left">Cardiac decompensation</td>
                <td align="center">15 (50.00)</td>
              </tr>
              <tr>
                <td align="left">APE</td>
                <td align="center">0</td>
              </tr>
              <tr>
                <td align="left">IE</td>
                <td align="center">0</td>
              </tr>
              <tr>
                <td align="left">Sudden death<xref ref-type="table-fn" rid="TFN1">*</xref>
								</td>
                <td align="center">1 (3.33)</td>
              </tr>
              <tr>
                <td align="left">Need for invasive procedure</td>
                <td align="center">4 (13.33)</td>
              </tr>
              <tr>
                <td align="left">BMV</td>
                <td align="center">3 (75)</td>
              </tr>
              <tr>
                <td align="left">Ao stent</td>
                <td align="center">1 (25)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <label>*</label>
              <p>Severe mitral regurgitation. APE: acute pulmonary edema; IE: infectious endocarditis; BMV: balloon mitral valvoplasty; Ao: aorta.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>According to the CARPREG risk score, our population had the following percentages of complications: CARPREG 0, 46 patients (34.85%); CARPREG 1, 67 (57.76%); and CARPREG &gt; 1, 19 (14.39%). The pregnant women classified as CARPREG &gt; 1 had a significantly higher number of complications during pregnancy than those classified as the other CARPREG classes (p = 0.0013) (<xref ref-type="table" rid="t2">Table 2</xref>). The percentages of cardiovascular complications in the population studied, according to the CARPREG classes, were compared with those expected according to the original CARPREG risk score (<xref ref-type="fig" rid="f1">Figure 1</xref>).</p>
        <table-wrap id="t2">
          <label>Table 2</label>
          <caption>
            <title>Distribution of the gestations according to the occurrence of cardiovascular complications, as classified by the Cardiac Disease in Pregnancy (CARPREG) risk score</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th align="left" rowspan="2">
                  <bold>Risk categories</bold>
                </th>
                <th align="center" colspan="2" style="border-bottom-style:solid;border-bottom-width:thin">
                  <bold>Cardiovascular complications</bold>
                </th>
                <th align="center" rowspan="2">
                  <bold>p Value</bold>
                </th>
              </tr>
              <tr>
                <th align="center">
                  <bold>Present</bold>
                </th>
                <th align="center">
                  <bold>Absent</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">CARPREG 0</td>
                <td align="center">15.2</td>
                <td align="center"><sub>.</sub>8 8</td>
                <td align="center" rowspan="3">0.013</td>
              </tr>
              <tr>
                <td align="left">CARPREG 1</td>
                <td align="center">16.4</td>
                <td align="center">83.6</td>
              </tr>
              <tr>
                <td align="left">CARPREG&gt;1</td>
                <td align="center">42.1</td>
                <td align="center">57.9</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <fig id="f1">
          <label>Figure 1</label>
          <caption>
            <title>Percentage of complications expected during pregnancy according to the CARPREG risk score versus those found.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-106-04-0289-60028-gf01.jpg"/></fig>
        <p>Of the 132 pregnancies assessed to analyze risk predictors, the following were not cardiovascular complication predictors in pregnancy: maternal age (p = 0.071); number of visits to the HRPC (p = 0.344); maternal smoking (p = 0.327); SAH (p = 0.295); preeclampsia (p = 0.450); prenatal care beginning on the third trimester (p = 0.379); and valve prosthesis (p = 0.542). In addition, the non-cardiovascular diseases associated were not predictors of complication. On univariate analysis, the following factors were identified as risk predictors: need to initiate or change cardiac medication during pregnancy (p = 0.001); LHO (p = 0.018); cardiac complications prior to pregnancy (p = 0.002); ejection fraction &lt;40% (p = 0.038); and NYHA functional class III on the first visit to the HRPC (p = 0.011) (<xref ref-type="table" rid="t3">Table 3</xref>).</p>
        <table-wrap id="t3">
          <label>Table 3</label>
          <caption>
            <title>Univariate analysis of risk predictors of cardiovascular complications</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th align="left" rowspan="2">
                  <bold>Variables</bold>
                </th>
                <th align="center" colspan="2" style="border-bottom-style:solid;border-bottom-width:thin">
                  <bold>Cardiovascular complication</bold>
                </th>
                <th align="center" rowspan="2">
                  <bold>OR</bold>
                </th>
                <th align="center" rowspan="2">
                  <bold>95%CI</bold>
                </th>
                <th align="center" rowspan="2">
                  <bold>p Value</bold>
                </th>
              </tr>
              <tr>
                <th align="center">
                  <bold>Present(%)</bold>
                </th>
                <th align="center">
                  <bold>Absent (%)</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Drug treatment<xref ref-type="table-fn" rid="TFN2">*</xref>
								</td>
                <td align="center">35.4</td>
                <td align="center">65.6</td>
                <td align="center">4.57</td>
                <td align="center">1.84-11.35</td>
                <td align="center">0.001</td>
              </tr>
              <tr>
                <td align="left">Maternal smoking</td>
                <td align="center">29.4</td>
                <td align="center">70.6</td>
                <td align="center">1.86</td>
                <td align="center">0.59-5.86</td>
                <td align="center">0.327</td>
              </tr>
              <tr>
                <td align="left">SAH</td>
                <td align="center">13.0</td>
                <td align="center">87.0</td>
                <td align="center">0.56</td>
                <td align="center">0.15-2.05</td>
                <td align="center">0.295</td>
              </tr>
              <tr>
                <td align="left">Preeclampsia</td>
                <td align="center">08.3</td>
                <td align="center">91.7</td>
                <td align="center">0.34</td>
                <td align="center">0.43-2.80</td>
                <td align="center">0.450</td>
              </tr>
              <tr>
                <td align="left">LHO</td>
                <td align="center">60.9</td>
                <td align="center">39.1</td>
                <td align="center">3.04</td>
                <td align="center">1.35-6.86</td>
                <td align="center">0.018</td>
              </tr>
              <tr>
                <td align="left">Previous cardiac complications</td>
                <td align="center">38.6</td>
                <td align="center">61.4</td>
                <td align="center">3.65</td>
                <td align="center">1.59-8.41</td>
                <td align="center">0.002</td>
              </tr>
              <tr>
                <td align="left">EF &gt; 60%</td>
                <td align="center">18.5</td>
                <td align="center">81.5</td>
                <td align="center">2.38</td>
                <td align="center">1.34-5.42</td>
                <td align="center">0.038</td>
              </tr>
              <tr>
                <td align="left">NYHA class III</td>
                <td align="center">25.0</td>
                <td align="center">75.0</td>
                <td align="center">3.89</td>
                <td align="center">1.23-7.69</td>
                <td align="center">0.011</td>
              </tr>
              <tr>
                <td align="left">HRPC initiated on the 3rd trimester</td>
                <td align="center">15.4</td>
                <td align="center">84.6</td>
                <td align="center">1.34</td>
                <td align="center">0.50-3.57</td>
                <td align="center">0.379</td>
              </tr>
              <tr>
                <td align="left">Valve prosthesis</td>
                <td align="center">21.1</td>
                <td align="center">79.0</td>
                <td align="center">1.10</td>
                <td align="center">0.33-3.65</td>
                <td align="center">0.542</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <label>*</label>
              <p>Need to initiate/change cardiac medication. OR: odds ratio; 95%CI: 95% confidence interval; SAH: systemic arterial hypertension; LHO: left-heart obstruction; EF: ejection fraction; HRPC: high-risk prenatal care; CARPREG: Cardiac Disease in Pregnancy.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>On multivariate analysis, the following factors were independent risk predictors of cardiovascular complications that can influence maternal-fetal outcomes: need to initiate or change cardiac medication during pregnancy [p = 0.009; 95% confidence interval (95%CI): 0.058-0.408]; previous cardiac complications (p = 0.013; 95%CI: 0.401-0.342); and functional class III on the first prenatal visit (p=0.041; 95%CI: 0.032-0.134).</p>
        <p>The perinatal outcomes assessed in 129 pregnancies were as follows: 13 (10.07%) small for gestational age newborns and 34 (26.36%) premature babies (4 aged less than 30 weeks, 14 between 32 and 34 weeks, and 16 between 35 and 37 weeks). No association was found between those results and risk factors for maternal cardiovascular complications.</p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>The present study describes the profile of a population of pregnant women with heart disease, mainly rheumatic lesions, which are usual in the Brazilian population. A 22.72% prevalence of cardiovascular complications in pregnancy was found, a rate close to those found in this same institution in 1997<xref ref-type="bibr" rid="B7">7</xref> and at the Instituto do Cora&#231;&#227;o (Incor) of the Medical School of the S&#227;o Paulo University,<xref ref-type="bibr" rid="B8">8</xref> 23.9% and 23.5%, respectively. The most recent international studies have revealed a lower number of complications: a Canadian study has reported 13% of complications;<xref ref-type="bibr" rid="B4">4</xref> the ZAHARA I study, conducted in Holland in 2010,<xref ref-type="bibr" rid="B5">5</xref> reported a 7.6% incidence; and, even more recently, in 2013, an European collaborative study reported 10% of cardiovascular complications.<xref ref-type="bibr" rid="B9">9</xref> That difference in the complication rates as compared to international data can be partially explained by the difference in the characteristics of the populations studied. In addition, pregnant women with heart disease in developed countries are more likely to have earlier and easier access to prenatal follow-up, which did not happen in 75% of this study population.</p>
      <p>This study shows that the population of pregnant women with heart disease cared for at our institution did not change much in the past 17 years regarding etiology. Over half of this population (62%) had rheumatic heart disease, a percentage similar to that obtained by Bacha et al.<xref ref-type="bibr" rid="B7">7</xref> (56.8%) from 1990 to 1995. That percentage was also close to the one reported by &#193;vila et al.<xref ref-type="bibr" rid="B8">8</xref> when following 1,000 patients up at Incor during a similar period.</p>
      <p>Of the assessments for risk prediction of cardiovascular complications during pregnancy, only Siu et al.<xref ref-type="bibr" rid="B4">4</xref> and Tanous et al.<xref ref-type="bibr" rid="B10">10</xref> have included both congenital and acquired cardiac diseases, but with a greater prevalence of congenital heart diseases (74% in both studies). In other studies, all populations analyzed consisted of pregnant women with only congenital heart diseases.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref> Of the complications presented by our patients, the most frequent was cardiac decompensation (11.36%), a diagnosis that can be inaccurate, because, during pregnancy, the distinction between the physiological changes inherent in pregnancy and the signs of heart disease is difficult. The criteria used to consider cardiac decompensation, as discussed in the ZAHARA study,<xref ref-type="bibr" rid="B5">5</xref> need to be better defined and can explain the elevated percentage of complications in our study population as compared to that of other publications.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref>
			</p>
      <sec>
        <title>Comparison with the CARPREG risk score</title>
        <p>Although the total frequency of complications was greater in our patients, when assessing the incidence of cardiovascular complications by using the CARPREG risk score, risk overestimation was observed in the pregnant women classified as CARPREG 1 and &gt; 1. Our patients classified as CARPREG 1 had a 16.42% rate of complications as compared to the 27% proposed by the study by Siu et al.<xref ref-type="bibr" rid="B4">4</xref> Those classified as CARPREG &gt; 1 had a 42.11% rate of complications as compared to the 75% expected according to the same index. This can be due to the apparent lower severity of the heart diseases in our population of pregnant women.</p>
        <p>Similarly, the LHO in our population less often progressed to cardiac decompensation or other complications. While the mean mitral valve area in our group of patients was 1.62 cm<sup>2</sup> and that of the aortic valve was 1.4 cm<sup>2</sup>, those of the pregnant women followed up in the CARPREG study<xref ref-type="bibr" rid="B4">4</xref> were smaller, 1.3 and 0.9 cm<sup>2</sup>, respectively.</p>
        <p>The congenital diseases of the patients in this study, in addition to being less frequent, were less complex, reflecting the reduced number of patients with ventricular dysfunction and complex congenital heart diseases who reach the fertile age in the Brazilian population.</p>
        <p>Although the patients classified as CARPREG 1 and &gt; 1 had a lower percentage of complications than expected, the CARPREG 0 group had twice more complications than that expected according to the CARPREG risk score<xref ref-type="bibr" rid="B2">2</xref> (11.36%). This risk underestimation can reflect a late diagnosis of heart diseases in young women, pregnancy being the moment of the first diagnosis.</p>
        <p>Other studies conducted with other populations have also reported an overestimation of the risk for complications by the CARPREG risk score. The authors of the ZAHARA I study<xref ref-type="bibr" rid="B5">5</xref> have attributed that overestimation by the CARPREG risk score to the possibility that patients with acquired heart diseases had more severe lesions in the CARPREG study than in other studies and also to the criteria used to define cardiac decompensation. Tanous et al.<xref ref-type="bibr" rid="B10">10</xref> and Curtis et al.<xref ref-type="bibr" rid="B13">13</xref> have also observed overestimation by the CARPREG risk score when using it in their patients, and have suggested that population differences would account for that.</p>
        <p>The ZAHARA II study<xref ref-type="bibr" rid="B6">6</xref> has considered that CARPREG has a high prediction power for cardiac events in patients at moderate and high risk, but that it could underestimate the risk in patients classified as low risk.</p>
        <p>Regarding the presence of advanced functional class at the beginning of pregnancy, all studies, regardless of the population studied, indicate that variable as a risk predictor, similarly to that observed in our population. Since the studies by Bacha et al.,<xref ref-type="bibr" rid="B7">7</xref> that association of maternal complications has been reported in the presence of a baseline NYHA classification III or IV at the beginning of the prenatal care or when the pregnant woman has pulmonary hipertension.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>
				</p>
        <p>Maternal smoking did not prove to be an independent risk factor for maternal complications, which is in accordance with the observation of other authors.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> Khairy et al.,<xref ref-type="bibr" rid="B11">11</xref> however, have found an association of maternal smoking with maternal complications, indicating that a more careful interpretation is required regarding that habit.</p>
        <p>The variables identified on multivariate analysis as predictors of complication in that population are very evident on clinical practice. The need to initiate or change maternal medications during pregnancy was associated with maternal complications (odds ratio of 4.57), and can be interpreted as an equivalent to the need for intervention due to NYHA functional class worsening during the pregnancy-puerperal cycle.<xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>
				</p>
        <p>Other risk factors proposed in the CARPREG study, such as LHO, ventricular dysfunction and previous cardiac complications, were associated with maternal complications on univariate analysis, but were not considered significant in the logistic regression model<xref ref-type="bibr" rid="B13">13</xref>. The reduced number of patients with that condition in our study could explain that difference. This analysis suggests that, in populations in which rheumatic acquired heart diseases prevail, the LHO conditions, which actually predict cardiovascular complications in pregnancy, are those with mitral stenosis, mainly in the presence of severe valve area reduction.</p>
        <p>Regarding perinatal outcomes, approximately one quarter of the newborns were premature and/or small for the gestational age, which is usually the most direct complication of severe maternal complications, which lead to premature interruptions of pregnancy and a reduction in placental nutrition. However, of that population, only 4 newborns were extremely premature, and, probably because of that small number, we could not find the expected association with maternal outcomes.<xref ref-type="bibr" rid="B14">14</xref>
				</p>
      </sec>
      <sec>
        <title>Study limitations</title>
        <p>The obstetric factors were not controlled, which can have influenced the results of the present study.</p>
        <p>Siu et al.<xref ref-type="bibr" rid="B4">4</xref> have reported that, even in the presence of LHO, cyanosis and advanced NYHA functional class, women with heart disease and no other obstetric risk factor had a minimally increased risk of neonatal complications. In addition, no patient had cyanosis, and the number of women with advanced functional class was relatively small.</p>
      </sec>
      <sec>
        <title>Clinical implications</title>
        <p>The present study emphasizes the need for the early assessment of heart disease in pregnancy, that is, in young women. Our patients' mean age was 27 years, in accordance with the mean age described in almost all international studies. However, most of our patients arrive at the HRPC outpatient clinic from the second trimester on, and 40%, after the 20th gestational week. Those data show that our patients are referred to the reference center later. Regarding the quality of the patients' follow-up care and of the family planning offered, it is worth noting that most women were between their second and fifth pregnancy, and almost 12% of them were at least on their fifth pregnancy. Comparison with studies from developed countries, such as that by Siu et al.,<xref ref-type="bibr" rid="B4">4</xref> in which only 1% of the women were on their fifth pregnancy and most (58%) of them were on their first pregnancy, evidences the great difference between developed and developing countries regarding the prevention of cardiovascular complications based on effective prenatal counseling and family planning. Our patients most likely do not have a regular follow-up with a cardiologist, and, thus, receive poor information on the risks of pregnancy regarding their cardiac problems. Ideally, pregnancy should be fully planned to occur on an occasion of disease stability, and the obstetric follow-up should be initiated on the first trimester.<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref>
				</p>
        <p>Most severe rheumatic diseases should be treated, usually with invasive procedures, before pregnancy. This would reduce the need to use those procedures during pregnancy itself, diminishing maternal-fetal morbidity and mortality.<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref> Other patients with more severe forms and no possibility of effective treatment should be oriented to avoid pregnancy and should receive effective contraceptive counseling.<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref>
				</p>
        <p>The intermediate- and long-term prospective follow-up of a significant number of patients with severe heart diseases can provide a more adequate analysis of the near miss situations. In addition, it will enable the assessment of the disease impact on the quality of life, sexual and reproductive health, and long-term consequences of the overload pregnancy imposes on patients with impaired cardiac function. It will also contribute to the appearance of health policies aimed at that group of patients.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>In this study on pregnant women with heart disease, mostly rheumatic heart disease, the following independent risk factors for cardiovascular complications during pregnancy stood out: beginning or changing cardiac medication during pregnancy; cardiac complications prior to the gestational period; and NYHA functional class III at the beginning of prenatal follow-up. In addition, the use of CARPREG risk score in that population tended to underestimate the risk of patients classified as low risk and to overestimate the risk of those classified as moderate or high risk.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <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 article is part of the thesis of master submitted by Luciana Carvalho Martins, from UFMG.</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="SA1" xml:lang="pt">
    <front-stub>
      <title-group>
        <article-title>Predi&#231;&#227;o de Risco de Complica&#231;&#245;es Cardiovasculares em Gestantes Portadoras de Cardiopatia</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Martins</surname>
            <given-names>Luciana Carvalho</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Freire</surname>
            <given-names>Claudia Maria Vilas</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
          <xref ref-type="aff" rid="aff4">2</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Capuru&#231;u</surname>
            <given-names>Carolina Andrade Bragan&#231;a</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nunes</surname>
            <given-names>Maria do Carmo Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rezende</surname>
            <given-names>Cezar Alencar de Lima</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
        </contrib>
      </contrib-group>
      <aff id="aff3">
        <label>1</label>
        <institution content-type="original">Universidade Federal de Minas Gerais &#8211; UFMG, Belo Horizonte, MG &#8211; Brasil</institution>
      </aff>
      <aff id="aff4">
        <label>2</label>
        <institution content-type="original">Maternidade Odete Valadares - Funda&#231;&#227;o Hospitalar do Estado de Minas Gerais, Belo Horizonte, MG &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Claudia Maria Vilas Freire</bold>, Universidade Federal de Minas Gerais &#8211; UFMG. Rua Ivai 96, Serra. CEP 30210-520, Belo Horizonte, MG &#8211; Brasil E-mail: <email>claudiavilasfreire@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: Martins LC, Freire CMV, Rezende CAL; Obten&#231;&#227;o de dados: Martins LC, Freire CMV; An&#225;lise e interpreta&#231;&#227;o dos dados: Martins LC, Freire CMV, Capuru&#231;u CAB, Nunes MCP; An&#225;lise estat&#237;stica: Martins LC, Freire CMV, Capuru&#231;u CAB, Nunes MCP; Reda&#231;&#227;o do manuscrito: Rezende CAL; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Martins LC, Freire CMV, Nunes MCP, Rezende CAL.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesse</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>Cardiopatia na gravidez &#233; a primeira causa de morte materna n&#227;o obst&#233;trica. Poucos estudos brasileiros avaliaram o impacto da cardiopatia na gesta&#231;&#227;o. </p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Determinar os fatores de risco associados &#224;s complica&#231;&#245;es cardiovasculares e neonatais.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Foram avaliadas 132 gestantes cardiopatas, acompanhadas em um Setor de Gesta&#231;&#227;o de Alto Risco, de janeiro de 2005 a julho de 2010. Foram selecionadas vari&#225;veis que poderiam influenciar no desfecho materno/fetal: idade, paridade, tabagismo, etiologia, gravidade da cardiopatia, complica&#231;&#245;es card&#237;acas pr&#233;vias, cianose, classe funcional <italic>New York Heart Association</italic> (NYHA) &gt; II, disfun&#231;&#227;o/obstru&#231;&#227;o do ventr&#237;culo esquerdo, arritmia, mudan&#231;a de tratamento, in&#237;cio e n&#250;mero de consultas de pr&#233;-natal. Foi calculado, retrospectivamente, o &#237;ndice de risco materno-fetal de acordo com o <italic>Cardiac Disease in Pregnancy</italic> (CARPREG) no in&#237;cio do pr&#233;-natal. As pacientes foram estratificadas nas tr&#234;s categorias de risco do CARPREG.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>A cardiopatia reum&#225;tica foi a cardiopatia mais prevalente (62,12%). As complica&#231;&#245;es mais frequentes foram descompensa&#231;&#227;o card&#237;aca (11,36%) e arritmias (6,82%). Fatores associados &#224;s complica&#231;&#245;es cardiovasculares na an&#225;lise multivariada foram mudan&#231;a do tratamento (p = 0,009), complica&#231;&#245;es card&#237;acas pr&#233;vias (p = 0,013) e classe funcional III NYHA na primeira consulta pr&#233;-natal (p = 0,041). O porcentual de complica&#231;&#227;o cardiovascular foi 15,22% no grupo CARPREG 0; 16,42% no CARPREG 1; e 42,11% no CARPREG &gt;1 &#8722; diferentemente do estimado pelo &#237;ndice original: 5%, 27% e 75%, respectivamente. Na amostra, tivermos 26,36% de prematuridade.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>Os fatores de risco para complica&#231;&#227;o cardiovascular nessa popula&#231;&#227;o foram a mudan&#231;a de tratamento, as complica&#231;&#245;es card&#237;acas pr&#233;vias e a classe funcional III NYHA no in&#237;cio do acompanhamento pr&#233;-natal. O &#237;ndice CARPREG, nesta amostra, composta principalmente por pacientes com cardiopatia reum&#225;tica, superestimou o n&#250;mero de eventos em gestantes classificadas como CARPREG 1 e &gt; 1, e subestimou o risco em pacientes de baixo risco (CARPREG 0).</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Doen&#231;as Cardiovasculares / complica&#231;&#245;es</kwd>
        <kwd>Gestantes</kwd>
        <kwd>Fatores de Risco</kwd>
        <kwd>Insufici&#234;ncia Card&#237;aca</kwd>
        <kwd>Arritmias Card&#237;acas</kwd>
        <kwd>Cardiopatia Reum&#225;tica</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A mortalidade materna ainda &#233; muito alta no Brasil. Segundo dados do Banco de Dados do Sistema &#218;nico de Sa&#250;de (DATASUS), a raz&#227;o da mortalidade materna no Brasil, em 2007, foi de 77 por 100 mil nascidos vivos. A cardiopatia na gravidez &#233; a primeira causa de morte materna de proced&#234;ncia n&#227;o obst&#233;trica e a quarta causa de morte materna em geral.<xref ref-type="bibr" rid="B1">1</xref> O diagnostico pr&#233;vio da patologia card&#237;aca ou no in&#237;cio da gravidez &#233; fundamental para avaliar o risco materno-fetal, com impacto na abordagem e na estrat&#233;gia terap&#234;utica das pacientes. As outras causas de morte materna s&#227;o inerentes a essa condi&#231;&#227;o e, geralmente, imprevis&#237;veis, diferentemente da cardiopatia.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref>
				</p>
        <p>Muitos estudos investigaram fatores de risco para desfechos adversos e complica&#231;&#245;es card&#237;acas durante a gesta&#231;&#227;o em pacientes cardiopatas.<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B6">6</xref> No entanto, s&#227;o poucos os estudos brasileiros que avaliam esses aspectos.<xref ref-type="bibr" rid="B7">7</xref> O presente estudo teve como objetivo estabelecer a preval&#234;ncia e a etiologia das doen&#231;as card&#237;acas em gestantes atendidas em nosso centro de refer&#234;ncia; identificar as complica&#231;&#245;es maternas mais frequentes e as suas repercuss&#245;es nos resultados maternos e perinatais; e avaliar vari&#225;veis preditoras de risco de complica&#231;&#245;es card&#237;acas que podem influenciar no desfecho materno-fetal.</p>
        <p>Avaliou-se ainda o &#237;ndice de risco materno-fetal, designado <italic>Cardiac Disease in Pregnancy</italic> (CARPREG), desenvolvido por Siu et al.,<xref ref-type="bibr" rid="B4">4</xref> com objetivo de classificar o risco da gestante com doen&#231;a card&#237;aca, e observar os preditores de complica&#231;&#245;es card&#237;acas e neonatais nessa popula&#231;&#227;o, com caracter&#237;sticas originalmente diferentes da popula&#231;&#227;o estudada pelos autores do referido &#237;ndice de risco.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Participaram deste estudo pacientes gr&#225;vidas cardiopatas acompanhadas desde a assist&#234;ncia pr&#233;-natal, no parto e puerp&#233;rio pela equipe do Setor de Assist&#234;ncia &#224;s Gesta&#231;&#245;es de Alto Risco entre janeiro de 2005 e julho de 2010. O total de 153 pacientes passou pelo setor durante esse per&#237;odo. O estudo foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa e as pacientes assinaram o Termo de Consentimento Livre e Esclarecido.</p>
        <p>Todas as gr&#225;vidas foram examinadas pelo mesmo cardiologista e se submeteram aos exames indicados para confirma&#231;&#227;o do diagn&#243;stico, classifica&#231;&#227;o e avalia&#231;&#227;o da gravidade da les&#227;o card&#237;aca, incluindo ecodopplercardiograma, eletrocardiograma e Holter-24 horas.</p>
        <p>Para a an&#225;lise dos preditores de risco de complica&#231;&#245;es card&#237;acas maternas, a partir dessa coorte hist&#243;rica, foram inclu&#237;das neste estudo apenas as pacientes cujas informa&#231;&#245;es eram completas, excluindo-se as que evolu&#237;ram para abortamento (perda fetal com menos de 20 semanas), as que tiveram partos em outras institui&#231;&#245;es e as gesta&#231;&#245;es gemelares. Tamb&#233;m foram exclu&#237;das as pacientes com cardiomiopatia periparto desenvolvidas no puerp&#233;rio. Assim, foram inclu&#237;das 132 das 153 pacientes gr&#225;vidas cardiopatas acompanhadas no setor.</p>
        <sec>
          <title>Vari&#225;veis analisadas</title>
          <p>Os poss&#237;veis fatores preditores de risco para complica&#231;&#245;es cardiovasculares maternas testados foram idade; paridade; n&#250;mero de consultas no pr&#233;-natal de alto risco (PNAR); in&#237;cio de PNAR no terceiro trimestre; tabagismo; complica&#231;&#245;es card&#237;acas pr&#233;vias e tratamentos cardiol&#243;gico cir&#250;rgico ou cl&#237;nico pr&#233;vios; necessidade de iniciar ou mudar tratamento medicamentoso durante a gesta&#231;&#227;o em pacientes que mudaram no m&#225;ximo uma classe funcional durante o acompanhamento, ou ajuste de dose para seguir um protocolo de acompanhamento; pr&#243;tese valvar; classe funcional da <italic>New York Heart Association</italic> (NYHA) &#8805; III no in&#237;cio do acompanhamento do PNAR; disfun&#231;&#227;o sist&#243;lica ventricular Esquerda (VE); pr&#233;-ecl&#226;mpsia ou hipertens&#227;o arterial sist&#234;mica (HAS) associada; doen&#231;as obstrutivas do lado esquerdo do cora&#231;&#227;o (DOLEC); e &#237;ndice CARPREG calculado. Foram agrupadas como DOLEC as seguintes doen&#231;as: estenose mitral com &#225;rea valvar &lt; 2,0 cm<sup>2</sup>, estenose a&#243;rtica com &#225;rea valvar &lt; 1,5 cm<sup>2</sup> e gradiente de pico na via de sa&#237;da do VE &gt; 30 mmHg.</p>
          <p>As vari&#225;veis avaliadas relativas &#224; gesta&#231;&#227;o atual foram: idade gestacional de in&#237;cio e n&#250;mero de consultas de pr&#233;-natal; complica&#231;&#245;es card&#237;acas durante a gesta&#231;&#227;o; procedimentos invasivos necess&#225;rios durante o pr&#233;-natal; classifica&#231;&#227;o funcional conforme a NYHA; doen&#231;as associadas (comorbidades); tipo de parto; tempo de interna&#231;&#227;o e complica&#231;&#245;es obst&#233;tricas. Quanto &#224;s vari&#225;veis neonatais, foram registrados a idade gestacional no parto e o peso ao nascimento.</p>
          <p>Foi calculado, retrospectivamente, para cada paciente, o &#237;ndice de predi&#231;&#227;o de risco de complica&#231;&#245;es relacionadas &#224; gravidez em mulheres com doen&#231;a card&#237;aca, o CARPREG. As vari&#225;veis relacionadas a complica&#231;&#245;es cardiovasculares pelo &#237;ndice CARPREG est&#227;o definidas no <xref ref-type="table" rid="t8">quadro 1</xref>. As gestantes s&#227;o classificadas como CARPREG 0, 1 ou &gt; 1 na vig&#234;ncia de nenhum, um ou mais do que um dos fatores de risco definidos.<xref ref-type="bibr" rid="B4">4</xref> As pacientes foram distribu&#237;das em tr&#234;s grupos: CARPREG 0, CARPREG 1 e CARPREG &gt; 1, e o porcentual de complica&#231;&#245;es ocorrido em cada grupo foi comparado ao predito pelo &#237;ndice original: 5, 27 e 75%, respectivamente.</p>
          <table-wrap id="t8">
            <label>Quadro 1</label>
            <caption>
              <title>&#205;ndice de risco Cardiac Disease in Pregnancy (CARPREG). NYHA: New York Heart Association; DOLEC: doen&#231;as obstrutivas do lado esquerdo do cora&#231;&#227;o.</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th align="left">
                    <bold>Preditores de eventos cardiovasculares</bold>
                  </th>
                  <th align="center">
                    <bold>Pontua&#231;&#227;o</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Evento card&#237;aco pr&#233;vio (fal&#234;ncia cardiaca, ataque isqu&#233;mico transit&#243;rio, infarto antes da gravidez ou arritmia)</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">Classe funcional de NYHA basal &gt; II ou cianose</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">DOLEC (valva mitral com &#225;rea &lt; 2 cm<sup>2</sup>, valva a&#243;rtica com &#225;rea &lt; 1,5 cm<sup>2</sup> ou gradiente de pico de fluxo de sa&#237;da &gt; 30 mmHg)</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">Fun&#231;&#227;o ventricular sist&#243;lica reduzida (fra&#231;&#227;o de eje&#231;&#227;o &lt; 40%)</td>
                  <td align="center">1</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
        <sec>
          <title>Defini&#231;&#227;o dos desfechos</title>
          <p>Complica&#231;&#245;es card&#237;acas foram descritas de acordo as defini&#231;&#245;es previamente propostas por Siu et al.<xref ref-type="bibr" rid="B4">4</xref>. Foram consideradas complica&#231;&#245;es card&#237;acas morte devido &#224; cardiopatia, fal&#234;ncia card&#237;aca com edema agudo de pulm&#227;o (documentado em raios X de t&#243;rax ou crepita&#231;&#245;es pulmonares bilaterais auscultadas em t&#243;rax posterior ao exame cl&#237;nico), infarto agudo do mioc&#225;rdio, taquiarritmia sintom&#225;tica sustentada ou bradiarritmia requerendo tratamento, piora maior ou igual a duas classes funcionais de NYHA comparada com a de base ou necessidade de procedimento invasivo de urg&#234;ncia durante a gravidez.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>A an&#225;lise estat&#237;stica foi realizada no programa <italic>Statistical Package for the Social Science</italic> (SPSS 17, Inc., Chicago, IL, Estados Unidos). Os dados cont&#237;nuos foram apresentados como m&#233;dia &#177; desvio padr&#227;o e os categ&#243;ricos como frequ&#234;ncia e porcentagem.</p>
          <p>As vari&#225;veis analisadas foram comparadas entre as gestantes que apresentaram complica&#231;&#245;es cardiovasculares na gesta&#231;&#227;o com as demais, que apresentaram evolu&#231;&#227;o favor&#225;vel por meio do teste qui quadrado (vari&#225;veis categ&#243;ricas) ou do teste <italic>t</italic> de Student n&#227;o pareado (vari&#225;veis cont&#237;nuas com distribui&#231;&#227;o normal).</p>
          <p>An&#225;lises de regress&#227;o log&#237;stica univariada e multivariada foram realizadas para se identificarem as vari&#225;veis associadas &#224;s complica&#231;&#245;es cardiovasculares na gesta&#231;&#227;o. O crit&#233;rio para sele&#231;&#227;o de vari&#225;veis no modelo multivariado foi relev&#226;ncia cl&#237;nica ou com p &lt; 0,20 na an&#225;lise univariada. O valor de p &lt; 0,05 foi considerado significante estatisticamente.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>A idade materna variou de 16 a 45 anos (m&#233;dia: 27,59 &#177; 7,17). Quanto ao n&#250;mero de gesta&#231;&#245;es, 50 pacientes (37,88%) eram primigestas, 38 (28,79%) eram secundigestas, 44 (33,33%) tiveram tr&#234;s ou mais gravidezes &#8722; dentre estas, 15 (11,36%) delas estavam na quinta gesta&#231;&#227;o ou mais.</p>
        <p>O acompanhamento no ambulat&#243;rio de PNAR foi iniciado no primeiro trimestre por apenas 34 (25,75%) pacientes. A maioria (79; 59,85%) iniciou o pr&#233;-natal no segundo trimestre e as demais 19 (14,40%) s&#243; no terceiro trimestre.</p>
        <p>Quanto ao diagn&#243;stico principal da cardiopatia, a popula&#231;&#227;o de estudo apresentou 82 (62,12%) pacientes com cardiopatias reum&#225;ticas, 18 (13,65%) com cardiopatias cong&#234;nitas, 15 (11,36%) de arritmias, seguidas de prolapso de valva mitral em seis (4,54%). As cardiomiopatias de causas diversas e outras doen&#231;as card&#237;acas somaram 11 (8,33%) casos.</p>
        <p>Entre as 82 gesta&#231;&#245;es em pacientes com cardiopatia reum&#225;tica, 19 (23,17%) eram em portadoras de pr&#243;tese valvar, sendo 14 (73,68%) pr&#243;teses normofuncionantes e cinco com disfun&#231;&#227;o residual ou les&#245;es associadas em outras valvas. A pr&#243;tese biol&#243;gica em posi&#231;&#227;o mitral foi a mais frequente (13; 68,42%), seguida da pr&#243;tese mec&#226;nica mitral (3; 15,79%); duas pacientes tinham pr&#243;teses mec&#226;nicas mitroa&#243;rticas e apenas uma possu&#237;a pr&#243;tese mec&#226;nica a&#243;rtica.</p>
        <p>Dos 18 casos de cardiopatia cong&#234;nita, a maioria de nove casos (50%) foi defeito de <italic>shunt</italic>: comunica&#231;&#227;o interventricular, comunica&#231;&#227;o interatrial, defeito de septo atrioventricular e persist&#234;ncia do canal arterial. Desses, 50% foram corrigidos cirurgicamente previamente &#224; gesta&#231;&#227;o. Entre as DOLEC, uma paciente tinha valva a&#243;rtica bic&#250;spide, e uma gestante era portadora de coarta&#231;&#227;o da aorta e valva a&#243;rtica bic&#250;spide. Nenhuma les&#227;o foi corrigida cirurgicamente antes da gesta&#231;&#227;o. Doen&#231;as da valva pulmonar (estenose valvar pulmonar ou dupla les&#227;o pulmonar) somaram tr&#234;s pacientes (16,7%). Entre as cardiopatias cianog&#234;nicas, tr&#234;s pacientes foram acompanhadas, sendo que duas delas tinham anomalia de Ebstein n&#227;o corrigidas cirurgicamente e um caso de tetralogia de Fallot corrigido. Foi observado tamb&#233;m um caso de insufici&#234;ncia tric&#250;spide grave.</p>
        <p>Quinze pacientes (11,36%) apresentavam doen&#231;a arr&#237;tmica do cora&#231;&#227;o. Oito delas (53,33%) apresentavam Taquiarritmias Supraventriculares (TPSV, <italic>flutter</italic> ou Fibrila&#231;&#227;o Atrial &#8722; FA). As bradiarritmias (Bloqueio Atrioventricular &#8722; BAV e bloqueios fasciculares) somaram quatro casos (26,67 %), e tr&#234;s pacientes apresentaram outras arritmias.</p>
        <p>Entre as pacientes, 20 (15,15%) fumavam uma m&#233;dia de 8,63 &#177; 8,95 cigarros por dia (5 a 40 cigarros). Dentre as tabagistas, 31,5% fumavam mais de dez cigarros por dia. Em rela&#231;&#227;o a comorbidades associadas, 23 pacientes (17,42%) apresentavam alguma comorbidade: duas eram diab&#233;ticas tipo I, 11 apresentavam DPOC /asma, quatro tinham doen&#231;as da tireoide, uma nefropata, tr&#234;s eram epil&#233;pticas, uma tinha dermatomiosite e outra tinha megaes&#244;fago.</p>
        <p>Em 132 gravidezes, 57 (43,18%) tiveram complica&#231;&#245;es cardiovasculares pr&#233;vias &#224; gesta&#231;&#227;o atual. A descompensa&#231;&#227;o card&#237;aca, seguida de arritmias, foi a complica&#231;&#227;o mais frequente.</p>
        <p>Das pacientes, 46 (34,85%) apresentavam DOLEC e, dessas, 44 (95,65%) eram portadoras de estenose mitral reum&#225;tica, com &#225;rea valvar m&#233;dia de 1,60 cm<sup>2</sup>, sendo que 11 delas (25,00%) foram consideradas com estenose grave.</p>
        <p>Quanto &#224; classe funcional da NYHA na primeira consulta de pr&#233;-natal, apenas quatro pacientes (3,3%) foram classificadas como classe funcional III. Dessas, tr&#234;s (75%) foram pacientes com estenose mitral moderada ou grave associadas &#224; regurgita&#231;&#227;o mitral moderada. Houve um caso de cardiomiopatia dilatada.</p>
        <p>Duas pacientes apresentaram fra&#231;&#227;o de eje&#231;&#227;o basal do VE inferior a 40%; 18 pacientes (13,63%) apresentavam fra&#231;&#227;o de eje&#231;&#227;o entre 40 e 60%. Os demais tinham FE normal &#8805; 60%.</p>
        <sec>
          <title>Desfechos adversos</title>
          <p>As complica&#231;&#245;es cardiovasculares ocorreram em 30 (22,72%) gestantes. A descompensa&#231;&#227;o card&#237;aca, diagnosticada pela piora de dois n&#237;veis na classe funcional da NYHA, ou piora em pacientes com classe funcional III basal foi a complica&#231;&#227;o mais frequente: 15 casos (11,36%). Arritmias card&#237;acas ocorreram em nove (6,82%) pacientes. Houve necessidade de procedimentos invasivos durante a gesta&#231;&#227;o em quatro casos (3,03%), sendo um implante de stent em coarta&#231;&#227;o da aorta e tr&#234;s valvoplastias mitral percut&#226;neas por cateter-bal&#227;o em pacientes com estenose mitral grave. Houve uma morte s&#250;bita no per&#237;odo p&#243;s-parto &#8722; de uma paciente com insufici&#234;ncia mitral grave e insufici&#234;ncia a&#243;rtica grave, portadora de s&#237;ndrome nefr&#243;tica (<xref ref-type="table" rid="t5">Tabela 1</xref>).</p>
          <table-wrap id="t5">
            <label>Tabela 1</label>
            <caption>
              <title>Distribui&#231;&#227;o das gesta&#231;&#245;es pacientes de acordo com a ocorr&#234;ncia de complica&#231;&#245;es cardiovasculares</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th align="left">
                    <bold>Complica&#231;&#245;es cardiovasculares</bold>
                  </th>
                  <th align="center">
                    <bold>n (%)</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Arritmias</td>
                  <td align="center">8(26,67)</td>
                </tr>
                <tr>
                  <td align="left">AVC</td>
                  <td align="center">2 (6,67)</td>
                </tr>
                <tr>
                  <td align="left">Descompensa&#231;&#227;o cardiaca</td>
                  <td align="center">15 (50,00)</td>
                </tr>
                <tr>
                  <td align="left">EAP</td>
                  <td align="center">0</td>
                </tr>
                <tr>
                  <td align="left">EI</td>
                  <td align="center">0</td>
                </tr>
                <tr>
                  <td align="left">Morte s&#250;bita<xref ref-type="table-fn" rid="TFN3">*</xref>
									</td>
                  <td align="center">1 (3,33)</td>
                </tr>
                <tr>
                  <td align="left">Necessidade de procedimento invasivo</td>
                  <td align="center">4 (13,33)</td>
                </tr>
                <tr>
                  <td align="left">VMCB</td>
                  <td align="center">3 (75)</td>
                </tr>
                <tr>
                  <td align="left">Stent Ao</td>
                  <td align="center">1 (25)</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN3">
                <label>*</label>
                <p>Insufici&#234;ncia mitral grave. AVC: acidente vascular cerebral; EAP: edema agudo de pulm&#227;o; EI: endocardite infecciosa; VMCB: valvoplastia mitral por cateter bal&#227;o, Ao: aorta.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>De acordo com o &#237;ndice de CARPREG, nossa popula&#231;&#227;o apresentou complica&#231;&#245;es nas seguintes propor&#231;&#245;es: 46 pacientes (34,85%) foram classificadas como CARPREG 0, 67 (57,76%) como CARPREG 1, e 19 (14,39%) gestantes foram classificadas no grupo CARPREG &gt; 1. As gestantes com GARPREG &gt; 1 evolu&#237;ram com significativo maior n&#250;mero de complica&#231;&#245;es durante a gravidez do que as outras classes de CARPREG (p = 0,0013), como demonstrado na <xref ref-type="table" rid="t6">tabela 2</xref>. O porcentual de complica&#231;&#245;es cardiovasculares do grupo estudado, de acordo com as classes do CARPREG, foi comparado ao que era esperado pelo &#237;ndice CARPREG original (<xref ref-type="fig" rid="f2">Figura 1</xref>).</p>
          <table-wrap id="t6">
            <label>Tabela 2</label>
            <caption>
              <title>Distribui&#231;&#227;o das gesta&#231;&#245;es de acordo com a ocorr&#234;ncia de complica&#231;&#245;es cardiovasculares, conforme classifica&#231;&#227;o pelo &#237;ndice de Cardiac Disease in Pregnancy (CARPREG), encontradas em rela&#231;&#227;o &#224;s esperadas</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th align="left" rowspan="2">
                    <bold>Categorias de risco</bold>
                  </th>
                  <th align="center" colspan="2" style="border-bottom-style:solid;border-bottom-width:thin">
                    <bold>Complica&#231;&#227;o cardiovascular</bold>
                  </th>
                  <th align="center" rowspan="2">
                    <bold>Valor de p</bold>
                  </th>
                </tr>
                <tr>
                  <th align="center">
                    <bold>Presente</bold>
                  </th>
                  <th align="center">
                    <bold>Ausente</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">CARPREG 0</td>
                  <td align="center">15,2</td>
                  <td align="center">84,8</td>
                  <td align="center" rowspan="3">0,013</td>
                </tr>
                <tr>
                  <td align="left">CARPREG1</td>
                  <td align="center">16,4</td>
                  <td align="center">83,6</td>
                </tr>
                <tr>
                  <td align="left">CARPREG &gt;1</td>
                  <td align="center">42,1</td>
                  <td align="center">57,9</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <fig id="f2">
            <label>Figura 1</label>
            <caption>
              <title>Porcentual de complica&#231;&#245;es esperadas durante a gesta&#231;&#227;o pelo &#237;ndice de Cardiac Disease in Pregnancy (CARPREG) vs. as encontradas.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-106-04-0289-60028-gf01-pt.jpg"/></fig>
          <p>Entre as 132 gesta&#231;&#245;es avaliadas para an&#225;lise dos fatores preditores de risco, idade materna (p = 0,071), n&#250;mero de consultas no PNAR (p = 0,344), tabagismo (p = 0,327), HAS (p = 0,295), pr&#233;-ecl&#226;mpsia (p = 0,450), in&#237;cio do pr&#233;-natal no terceiro trimestre (p = 0,379) e pr&#243;tese valvar (p = 0,542) n&#227;o foram vari&#225;veis preditoras de complica&#231;&#245;es cardiovasculares na gesta&#231;&#227;o. As doen&#231;as n&#227;o cardiovasculares associadas tamb&#233;m n&#227;o foram preditoras de complica&#231;&#227;o. A necessidade de iniciar ou mudar o tratamento medicamentoso durante a gesta&#231;&#227;o (p = 0,001), DOLEC (p = 0,018), complica&#231;&#245;es card&#237;acas pr&#233;vias &#224; gesta&#231;&#227;o (p = 0,002), fra&#231;&#227;o de eje&#231;&#227;o &lt; 40% (p = 0,038) e classifica&#231;&#227;o da NYHA III na primeira consulta do PNAR (p = 0,011) foram identificados como fatores preditores de risco na an&#225;lise univariada (<xref ref-type="table" rid="t7">Tabela 3</xref>).</p>
          <table-wrap id="t7">
            <label>Tabela 3</label>
            <caption>
              <title>An&#225;lise univariada de fatores de risco preditores de complica&#231;&#245;es cardiovasculares</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th align="left">
                    <bold>Vari&#225;veis<xref ref-type="table-fn" rid="TFN4">*</xref></bold>
                  </th>
                  <th align="center" colspan="2" style="border-bottom-style:solid;border-bottom-width:thin">
                    <bold>Complica&#231;&#227;o cardiovascular</bold>
                  </th>
                  <th align="center" rowspan="2">
                    <bold>OR</bold>
                  </th>
                  <th align="center" rowspan="2">
                    <bold>IC95%</bold>
                  </th>
                  <th align="center" rowspan="2">
                    <bold>Valor de p</bold>
                  </th>
                </tr>
                <tr>
                  <th align="left">
									</th>
                  <th align="center">
                    <bold>Presente</bold>
                  </th>
                  <th align="center">
                    <bold>Ausente</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Tratamento medicamentoso</td>
                  <td align="center">35,4</td>
                  <td align="center">65,6</td>
                  <td align="center">4,57</td>
                  <td align="center">1,84-11,35</td>
                  <td align="center">0,001</td>
                </tr>
                <tr>
                  <td align="left">Tabagismo</td>
                  <td align="center">29,4</td>
                  <td align="center">70,6</td>
                  <td align="center">1,86</td>
                  <td align="center">0,59-5,86</td>
                  <td align="center">0,327</td>
                </tr>
                <tr>
                  <td align="left">HAS</td>
                  <td align="center">13,0</td>
                  <td align="center">87,0</td>
                  <td align="center">0,56</td>
                  <td align="center">0,15-2,05</td>
                  <td align="center">0,295</td>
                </tr>
                <tr>
                  <td align="left">Pr&#233;-ecl&#226;mpsia</td>
                  <td align="center">08,3</td>
                  <td align="center">91,7</td>
                  <td align="center">0,34</td>
                  <td align="center">0,43-2,80</td>
                  <td align="center">0,450</td>
                </tr>
                <tr>
                  <td align="left">DOLEC</td>
                  <td align="center">60,9</td>
                  <td align="center">39,1</td>
                  <td align="center">3,04</td>
                  <td align="center">1,35-6,86</td>
                  <td align="center">0,018</td>
                </tr>
                <tr>
                  <td align="left">Complica&#231;&#245;es card&#237;acas pr&#233;vias</td>
                  <td align="center">38,6</td>
                  <td align="center">61,4</td>
                  <td align="center">3,65</td>
                  <td align="center">1,59-8,41</td>
                  <td align="center">0,002</td>
                </tr>
                <tr>
                  <td align="left">FE &gt; 60%</td>
                  <td align="center">18,5</td>
                  <td align="center">81,5</td>
                  <td align="center">2,38</td>
                  <td align="center">1,34-5,42</td>
                  <td align="center">0,038</td>
                </tr>
                <tr>
                  <td align="left">NYHA classe III</td>
                  <td align="center">25,0</td>
                  <td align="center">75,0</td>
                  <td align="center">3,89</td>
                  <td align="center">1,23-7,69</td>
                  <td align="center">0,011</td>
                </tr>
                <tr>
                  <td align="left">PNAR iniciado no 3&#176; trimestre</td>
                  <td align="center">15,4</td>
                  <td align="center">84,6</td>
                  <td align="center">1,34</td>
                  <td align="center">0,50-3,57</td>
                  <td align="center">0,379</td>
                </tr>
                <tr>
                  <td align="left">Pr&#243;tese valvar</td>
                  <td align="center">21,1</td>
                  <td align="center">79,0</td>
                  <td align="center">1,10</td>
                  <td align="center">0,33-3,65</td>
                  <td align="center">0,542</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN4">
                <label>*</label>
                <p>Porcentagem. Necessidade de iniciar/ modificar tratamento medicamentoso. OR: odds ratio; IC95%: intervalo de confian&#231;a de 95%; HAS: hipertens&#227;o arterial sist&#234;mica; DOLEC: doen&#231;a obstrutiva do lado esquerdo do cora&#231;&#227;o; FE: fra&#231;&#227;o de eje&#231;&#227;o; PNAR: pr&#233;-natal de alto risco; CARPREG: Cardiac Disease in Pregnancy.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>Na an&#225;lise multivariada, a necessidade de iniciar ou mudar o tratamento medicamentoso durante a gesta&#231;&#227;o (p = 0,009; Intervalo de Confian&#231;a de 95% - IC95%: 0,058-0,408), complica&#231;&#245;es card&#237;acas pr&#233;vias (p = 0,013; IC95%: 0,401-0,342) e classe funcional III na primeira consulta do pr&#233;-natal (p = 0,041; IC95%: 0,032-0,134) foram fatores de risco preditores independentes de complica&#231;&#245;es cardiovasculares que podem influenciar no desfecho materno-fetal.</p>
          <p>Os resultados perinatais foram avaliados em 129 gesta&#231;&#245;es e verificamos 13 (10,07%) rec&#233;m-nascidos Pequenos para Idade Gestacional (PIG) e 34 (26,36%) prematuros, isto &#233;, (quatro com menos de 30 semanas, 14 entre 32 e 34 semanas, 16 entre 35 e 37 semanas). N&#227;o foi encontrada associa&#231;&#227;o dessas complica&#231;&#245;es com fatores de risco para complica&#231;&#245;es cardiovasculares maternas.</p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>O presente estudo traz a descri&#231;&#227;o do perfil de uma popula&#231;&#227;o de gestantes cardiopatas com predom&#237;nio de les&#245;es reum&#225;ticas, habitual em nossa popula&#231;&#227;o. Foi encontrada preval&#234;ncia de 22,72% de complica&#231;&#245;es cardiovasculares na gesta&#231;&#227;o, taxa pr&#243;xima &#224; encontrada nessa mesma institui&#231;&#227;o em 1997<xref ref-type="bibr" rid="B7">7</xref> e no Instituto do Cora&#231;&#227;o (Incor) da Faculdade de Medicina da Universidade de S&#227;o Paulo:<xref ref-type="bibr" rid="B8">8</xref> 23,9% e 23,5% de complica&#231;&#245;es cardiovasculares, respectivamente. Os dados internacionais mais recentes revelam um n&#250;mero mais baixo de complica&#231;&#245;es: estudo canadense registrou 13% de complica&#231;&#245;es;<xref ref-type="bibr" rid="B4">4</xref> o estudo ZAHARA I, realizado na Holanda, em 2010,<xref ref-type="bibr" rid="B5">5</xref> encontrou incid&#234;ncia de 7,6% e, mais recente ainda, em 2013, foi encontrado 10% de complica&#231;&#245;es cardiovasculares num estudo colaborativo europeu.<xref ref-type="bibr" rid="B9">9</xref> Essa diferen&#231;a de complica&#231;&#245;es em rela&#231;&#227;o aos dados internacionais pode ser explicada, em parte, pela diferen&#231;a das caracter&#237;sticas das popula&#231;&#245;es em estudo. Al&#233;m disso, provavelmente, gestantes cardiopatas em pa&#237;ses desenvolvidos, disp&#245;em de acesso mais precoce e facilitado para acompanhamento pr&#233;-natal, o que n&#227;o aconteceu em 75% dessa popula&#231;&#227;o.</p>
        <p>Esta pesquisa mostra que a popula&#231;&#227;o de gr&#225;vidas cardiopatas assistidas por nossa institui&#231;&#227;o n&#227;o mudou muito nos &#250;ltimos 17 anos em rela&#231;&#227;o a etiologia. Mais da metade dessa popula&#231;&#227;o (62%) tinha cardiopatia reum&#225;tica, porcentual semelhante ao obtido por Bacha et al.,<xref ref-type="bibr" rid="B7">7</xref> no per&#237;odo de 1990 a 1995, cuja propor&#231;&#227;o foi de 56,8%. Esse porcentual tamb&#233;m foi bastante pr&#243;ximo do registrado por &#193;vila et al.<xref ref-type="bibr" rid="B8">8</xref> em 1.000 pacientes acompanhados no Incor em per&#237;odo semelhante.</p>
        <p>Das avalia&#231;&#245;es de predi&#231;&#227;o de risco de complica&#231;&#245;es cardiovasculares durante a gesta&#231;&#227;o, Siu et al.<xref ref-type="bibr" rid="B4">4</xref> e Tanous et al.<xref ref-type="bibr" rid="B10">10</xref> foram os &#250;nicos que inclu&#237;ram tanto doen&#231;as card&#237;acas cong&#234;nitas quanto as adquiridas, mas com a maioria composta por cardiopatias cong&#234;nitas: 74% em ambos. Nos demais estudos, todas as popula&#231;&#245;es analisadas consistiam de gestantes portadoras apenas de cardiopatias cong&#234;nitas.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref> Das complica&#231;&#245;es apresentadas por nossas pacientes, a mais frequentemente constatada foi a descompensa&#231;&#227;o card&#237;aca, com 11,36%. No entanto, esse diagn&#243;stico &#233;, por vezes, impreciso, uma vez que, na gesta&#231;&#227;o, &#233; dif&#237;cil a distin&#231;&#227;o entre as altera&#231;&#245;es fisiol&#243;gicas pr&#243;prias da gravidez e os sinais de doen&#231;a card&#237;aca. Os crit&#233;rios usados para considerar descompensa&#231;&#227;o card&#237;aca, conforme discutido no estudo ZAHARA,<xref ref-type="bibr" rid="B5">5</xref> precisam ser mais bem definidos e podem explicar o elevado porcentual de complica&#231;&#245;es em nossa popula&#231;&#227;o, em rela&#231;&#227;o a outras publica&#231;&#245;es.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref>
				</p>
        <sec>
          <title>Compara&#231;&#227;o com o &#237;ndice CARPREG</title>
          <p>Apesar da frequ&#234;ncia total de complica&#231;&#245;es ter sido mais alta em nossas pacientes, quando se avaliou a incid&#234;ncia de complica&#231;&#245;es cardiovasculares pelo &#237;ndice CARPREG, verificou-se que houve superestima&#231;&#227;o do risco por esse &#237;ndice na popula&#231;&#227;o do estudo em gestantes CARPREG classe 1 e &gt; 1. Nossas pacientes, que foram classificadas como CARPREG 1, tiveram 16,42% de complica&#231;&#245;es vs. os 27% propostos pelo estudo de Siu et al.;<xref ref-type="bibr" rid="B4">4</xref> e as classificadas como CARPREG &gt; 1 tiveram cerca de 42,11% de complica&#231;&#245;es cardiovasculares vs. 75% do esperado pelo mesmo &#237;ndice. Este resultado pode ser explicado pelo fato de nossa popula&#231;&#227;o ser, aparentemente, constitu&#237;da por gestantes com cardiopatias de menor gravidade.</p>
          <p>Da mesma forma, as DOLEC, em nossa popula&#231;&#227;o, evolu&#237;ram com menor frequ&#234;ncia de descompensa&#231;&#227;o card&#237;aca ou outras complica&#231;&#245;es. Enquanto a &#225;rea valvar mitral m&#233;dia do nosso grupo de pacientes foi de 1,62 cm<sup>2</sup> e de 1,4 cm<sup>2</sup> para &#225;rea da valva a&#243;rtica, as gestantes acompanhadas no estudo CARPREG<xref ref-type="bibr" rid="B4">4</xref> apresentaram menores &#225;reas valvares m&#233;dias, de 1,3 e 0,9 cm<sup>2</sup>, respectivamente.</p>
          <p>As doen&#231;as cong&#234;nitas apresentadas pelas pacientes desta investiga&#231;&#227;o, al&#233;m de menos frequentes, foram menos complexas, refletindo o reduzido n&#250;mero de pacientes com disfun&#231;&#227;o ventricular e com cardiopatias cong&#234;nitas complexas que chegam a idade procriativa em nossa popula&#231;&#227;o.</p>
          <p>Apesar das pacientes classificadas como CARPREG 1 e &gt; 1 terem tido porcentual de complica&#231;&#245;es mais baixo do que o esperado, o grupo de CARPREG 0 apresentou duas vezes mais complica&#231;&#245;es do que o esperado pelo &#237;ndice CARPREG<xref ref-type="bibr" rid="B2">2</xref> (11,36%). Essa subestima&#231;&#227;o do risco pode refletir diagn&#243;stico tardio de cardiopatias em mulheres jovens, sendo a gesta&#231;&#227;o o momento do primeiro diagn&#243;stico.</p>
          <p>Outros estudos realizados em outras popula&#231;&#245;es tamb&#233;m relataram superestima&#231;&#227;o do risco de complica&#231;&#245;es pelo &#237;ndice de CARPREG. Os autores do ZAHARA I<xref ref-type="bibr" rid="B5">5</xref> atribu&#237;ram essa superestima&#231;&#227;o do &#237;ndice CARPREG &#224; possibilidade de as pacientes com cardiopatias adquiridas apresentarem les&#245;es de maior gravidade no estudo CARPREG do que nos outros estudos e aos crit&#233;rios usados para definir descompensa&#231;&#227;o card&#237;aca. Tanous et al.<xref ref-type="bibr" rid="B10">10</xref> e Curtis et al.<xref ref-type="bibr" rid="B13">13</xref> tamb&#233;m observaram superestima&#231;&#227;o do &#237;ndice de CARPREG quando o utilizaram em suas pacientes e sugeriram que as diferen&#231;as populacionais seriam o fator primordial para esses resultados.</p>
          <p>O ZAHARA II<xref ref-type="bibr" rid="B6">6</xref> considerou que o CARPREG tem alto poder de predi&#231;&#227;o de eventos card&#237;acos para casos de moderado e alto risco, mas que poderia subestimar o risco em pacientes classificadas como baixo risco.</p>
          <p>Em rela&#231;&#227;o &#224; presen&#231;a de classe funcional elevada ao in&#237;cio da gesta&#231;&#227;o, todos os estudos, independentemente da popula&#231;&#227;o estudada, apontam essa vari&#225;vel como preditora de risco, assim como em nossa popula&#231;&#227;o. Desde os estudos de Bacha et al.,<xref ref-type="bibr" rid="B7">7</xref> essa associa&#231;&#227;o de complica&#231;&#245;es maternas &#233; apontada quando a gestante tinha classifica&#231;&#227;o NYHA III ou IV logo no inicio do pr&#233;-natal ou era portadora de hipertens&#227;o pulmonar .<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>
					</p>
          <p>O tabagismo n&#227;o mostrou ser fator de risco independente para complica&#231;&#245;es maternas, o que foi tamb&#233;m observado por alguns autores.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> Khairy et al.,<xref ref-type="bibr" rid="B11">11</xref> entretanto, encontraram associa&#231;&#227;o do tabagismo com complica&#231;&#245;es maternas, indicando que uma interpreta&#231;&#227;o mais cuidadosa deve ser feita em rela&#231;&#227;o a esse h&#225;bito.</p>
          <p>As vari&#225;veis apontadas na an&#225;lise multivariada como preditoras de complica&#231;&#227;o nessa popula&#231;&#227;o s&#227;o muito evidentes na pr&#225;tica cl&#237;nica. A necessidade de iniciar ou mudar as medica&#231;&#245;es durante a gesta&#231;&#227;o se associou &#224;s complica&#231;&#245;es maternas, com de OR 4,57, e pode ser interpretada como um equivalente da necessidade de interven&#231;&#227;o por piora da classe funcional de NYHA, durante o ciclo grav&#237;dico-puerperal.<xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>
					</p>
          <p>Outros fatores de risco propostos pelo estudo CARPREG, como DOLEC, disfun&#231;&#227;o ventricular e complica&#231;&#245;es card&#237;acas pr&#233;vias, foram associados &#224;s complica&#231;&#245;es maternas na an&#225;lise univariada, mas n&#227;o foram considerados significativas no modelo de regress&#227;o log&#237;stica<xref ref-type="bibr" rid="B13">13</xref>. Provavelmente, o reduzido n&#250;mero de casos com essas altera&#231;&#245;es na nossa s&#233;rie de casos poderia explicar essa diferen&#231;a. Essa an&#225;lise sugere que, em popula&#231;&#245;es em que as cardiopatias adquiridas reum&#225;ticas s&#227;o ainda a maioria, as DOLEC, que realmente predizem complica&#231;&#245;es cardiovasculares na gesta&#231;&#227;o, s&#227;o as com predomin&#226;ncia de estenose mitral, principalmente quando a redu&#231;&#227;o da &#225;rea valvar for grave.</p>
          <p>Em rela&#231;&#227;o aos desfechos perinatais, cerca de um quarto dos rec&#233;m-nascidos foram prematuros e/ou de PIG, o que geralmente &#233; a complica&#231;&#227;o mais direta das complica&#231;&#245;es maternas graves, que levam a interrup&#231;&#245;es prematuras da gesta&#231;&#227;o e a redu&#231;&#227;o da nutri&#231;&#227;o placent&#225;ria. No entanto, nesta popula&#231;&#227;o, apenas quatro rec&#233;m-nascidos foram prematuros extremos e, provavelmente, devido ao baixo n&#250;mero, n&#227;o encontramos a associa&#231;&#227;o esperada com os desfechos maternos.<xref ref-type="bibr" rid="B14">14</xref>
					</p>
        </sec>
        <sec>
          <title>Limita&#231;&#245;es do estudo</title>
          <p>N&#227;o houve controle dos fatores obst&#233;tricos, o que pode ter influenciado nos resultados do presente estudo.</p>
          <p>Siu et al.<xref ref-type="bibr" rid="B4">4</xref> relataram que mesmo em caso de presen&#231;a de DOLEC, cianose e classe funcional de NYHA avan&#231;ada, mulheres cardiopatas sem outro fator de risco obst&#233;trico associado apresentaram risco minimamente aumentado de complica&#231;&#245;es neonatais. Al&#233;m disso, n&#227;o tivemos casos de pacientes com cianose e o n&#250;mero de mulheres com classe funcional avan&#231;ada tamb&#233;m foi relativamente baixo.</p>
        </sec>
        <sec>
          <title>Implica&#231;&#245;es cl&#237;nicas</title>
          <p>O presente estudo enfatiza a necessidade de avalia&#231;&#227;o precoce da cardiopatia no contexto da gravidez, isto &#233;, em mulheres jovens. A m&#233;dia de idade de nossas pacientes foi de 27 anos, condizente com a m&#233;dia de idade descrita por quase todos os estudos internacionais, mas a maioria delas chega ao ambulat&#243;rio de PNAR a partir do segundo trimestre, e 40% ap&#243;s a 20<sup>(a)</sup> semana de gesta&#231;&#227;o. Esse dados mostram que nossas pacientes s&#227;o encaminhadas mais tardiamente para o centro de refer&#234;ncia. Outro dado que chama a aten&#231;&#227;o para a qualidade do acompanhamento dessas pacientes e do planejamento familiar oferecido &#233; que a maioria estava entre a segunda e a quinta gesta&#231;&#227;o e, praticamente, 12% delas estavam na quinta gesta&#231;&#227;o ou mais. Comparados aos dados de pa&#237;ses desenvolvidos, como os de Siu et al.,<xref ref-type="bibr" rid="B4">4</xref> em que apenas 1% delas estava na quinta gesta&#231;&#227;o e a maioria (58%) na primeira gesta&#231;&#227;o, percebe-se a grande diferen&#231;a na preven&#231;&#227;o de complica&#231;&#245;es cardiovasculares a partir de aconselhamento pr&#233;-natal e planejamento familiar eficaz entre os pa&#237;ses desenvolvidos e os em desenvolvimento. &#201; prov&#225;vel que nossas pacientes n&#227;o tenham acompanhamento regular pelo cardiologista e, portanto, que recebam pouca informa&#231;&#227;o sobre os riscos da gesta&#231;&#227;o em rela&#231;&#227;o ao problema card&#237;aco. O ideal seria que a gravidez fosse plenamente planejada num momento de estabilidade da doen&#231;a, e que o acompanhamento obst&#233;trico j&#225; fosse iniciado em seu primeiro trimestre.<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref>
					</p>
          <p>Grande parte das doen&#231;as reum&#225;ticas graves deveria ser tratada, muitas vezes com procedimentos invasivos antes da gesta&#231;&#227;o. Isso evitaria esses procedimentos durante a pr&#243;pria gesta&#231;&#227;o, diminuindo a morbimortalidade materna e fetal.<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref> Outras pacientes com formas mais graves e sem possibilidade de tratamento eficaz deveriam ser desaconselhadas a engravidar e receberem prontamente m&#233;todos contraceptivos eficazes.<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref>
					</p>
          <p>O acompanhamento prospectivo de um n&#250;mero significativo de pacientes com cardiopatias graves a m&#233;dio e longo prazo pode proporcionar an&#225;lise mais adequada das situa&#231;&#245;es de quase perda (<italic>near miss)</italic>, e do impacto da doen&#231;a na qualidade de vida, sa&#250;de sexual e reprodutiva, e das consequ&#234;ncias a longo prazo da sobrecarga da gravidez &#224; paciente que tem comprometimento da fun&#231;&#227;o card&#237;aca, al&#233;m de contribuir para o surgimento de pol&#237;ticas de sa&#250;de voltadas para esse grupo de pacientes.</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Neste estudo em gestantes cardiopatas, com n&#237;tido predom&#237;nio de cardiopatia reum&#225;tica, o in&#237;cio ou a modifica&#231;&#227;o de tratamento medicamentoso durante a gesta&#231;&#227;o, ter apresentado complica&#231;&#245;es card&#237;acas pr&#233;vias ao per&#237;odo gestacional e estar em classe funcional III da NY HA no in&#237;cio do acompanhamento pr&#233;-natal foram fatores de risco independentes para complica&#231;&#245;es cardiovasculares durante a gesta&#231;&#227;o. Tamb&#233;m observamos que a utiliza&#231;&#227;o do &#237;ndice CARPREG nesta popula&#231;&#227;o tendeu a subestimar o risco nas pacientes classificadas como baixo risco e superestimar os riscos nas classificadas como de risco moderado ou elevado.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <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>Este artigo &#233; parte de Disserta&#231;&#227;o de Mestrado de Luciana Carvalho Martins pela UFMG.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
