<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "https://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" dtd-version="1.0" specific-use="sps-1.3" article-type="other" 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">wYWcy3DhvsrV55XZbQnV9pw</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2015002300328</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20150136</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Special Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Executive Summary of the Guidelines on Stable Coronary Disease</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>C&#233;sar</surname>
            <given-names>Luiz Antonio Machado</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mansur</surname>
            <given-names>Antonio de P&#225;dua</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ferreira</surname>
            <given-names>Jo&#227;o Fernando Monteiro</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">FM</institution>
        <institution content-type="orgdiv2">HC</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o (InCor) HC-FMUSP, S&#227;o Paulo, SP &#8211; Brasil</institution>
        <institution content-type="normalized">Universidade de S&#227;o Paulo</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><bold>Mailing Address: Luiz Antonio Machado C&#233;sar</bold>, Av. Dr. En&#233;as de Carvalho Aguiar, 44. Cerqueira Cesar, Postal Code 05403-000. S&#227;o Paulo, SP &#8211; Brazil Email: <email>luiz.cesar@incor.usp.br</email> </corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Writing of the manuscript and Critical revision of the manuscript for intellectual content: C&#233;sar LAM, Mansur AP, Ferreira JFM.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>Drs. Luiz Antonio Machado C&#233;sar and Jo&#227;o Fernando Monteiro Ferreira participated in clinical studies and / or experimental trials supported by Servier e Astra-Zeneca.</p>
          <p>Dr. Luiz Antonio Machado C&#233;sar has spoken at events or activities sponsored by Servier e Astra-Zeneca; It was (is) advisory board member or director of a Servier e Astra-Zeneca; Committees participated in completion of research sponsored by Servier e Astra-Zeneca; Personal or institutional aid received from Servier e Astra-Zeneca; Produced scientific papers in journals sponsored by Servier e Astra-Zeneca.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <month>10</month>
        <year>2015</year>
      </pub-date>
      <volume>105</volume>
      <issue>4</issue>
      <fpage>328</fpage>
      <lpage>338</lpage>
      <history>
        <date date-type="received">
          <day>23</day>
          <month>09</month>
          <year>2015</year>
        </date>
        <date date-type="rev-recd">
          <day>23</day>
          <month>09</month>
          <year>2015</year>
        </date>
        <date date-type="accepted">
          <day>23</day>
          <month>09</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>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Coronary Artery Disease</kwd>
        <kwd>Diagnosis</kwd>
        <kwd>Risk Factors</kwd>
        <kwd>Physical Examination</kwd>
        <kwd>Atherosclerosis</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec>
      <title>Part I &#8211; Diagnosis and risk stratification</title>
      <sec>
        <title>Introduction</title>
        <p>These guidelines aim to assist physicians, particularly cardiologists, to identify adults at high risk of coronary disease as early as possible, and to highlight its most common symptoms, especially coronary arery disease (CAD) symptoms.</p>
        <p>According to Brazilian&#8217;s Unified Health System database (DATASUS), cardiovascular causes represent nearly 30% of all causes of death in Brazil<xref ref-type="bibr" rid="B01">1</xref>.</p>
        <list list-type="bullet">
          <title>Recommendation levels:</title>
          <list-item>
            <p>Class I: conditions for which there is conclusive evidence or general agreement that the procedure is useful/effective;</p>
          </list-item>
          <list-item>
            <p>Class II: conditions for which there is conflicting evidence and/or divergence of opinion about the usefulness/efficacy of the procedure;</p>
          </list-item>
          <list-item>
            <p>Class IIa: weight of evidence/opinion in favor of usefulness/efficacy. Approved by the majority of the professionals;</p>
          </list-item>
          <list-item>
            <p>Class IIb: safety and usefulness/efficacy is less well established, with no predominance of opinion in favor of the procedure;</p>
          </list-item>
          <list-item>
            <p>Class III: conditions for which there is evidence and/or general agreement that the procedure is not useful or effective and in some cases may be harmful;</p>
          </list-item>
        </list>
        <list list-type="bullet">
          <title>Evidence level:</title>
          <list-item>
            <p>Level A: data derived from multiple consistent, large randomized clinical trials and/or robust systematic meta&#8209;analysis of randomized clinical trials.</p>
          </list-item>
          <list-item>
            <p>Level of evidence B: data derived from a less robust meta-analysis, a single randomized trial or nonrandomized (observational) studies.</p>
          </list-item>
          <list-item>
            <p>Level of evidence C: data derived from consensus opinion of experts.</p>
          </list-item>
        </list>
      </sec>
      <sec>
        <title>Diagnosis</title>
        <sec>
          <title>Diagnosis of subclinical coronary artery disease</title>
          <p>The risk of atherosclerotic disease may be measured by the sum of individual risks and by the synergism between the known risk factors for cardiovascular disease. Due to these complex interactions, an intuitive approach of risk attribution frequently lead to underestimation or overestimation of cases with higher or low risk, respectively.</p>
          <sec>
            <title>Diagnosis of symptomatic patients</title>
            <p>The approach proposed by Diamond and Forrester<xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B03">3</xref> (<xref ref-type="table" rid="t01">Table 1</xref>): Level of recommendation I, evidence level B was considered for diagnosis.</p>
            <table-wrap id="t01">
              <label>Table 1</label>
              <caption>
                <title>Pre-test probability of coronary artery disease in symptomatic patients by age and sex (Diamond/Forrester e CASS Data)</title>
              </caption>
              <table frame="hsides" rules="groups">
                <thead>
                  <tr style="border-bottom-width:thin;border-bottom-style:solid">
                    <th rowspan="2" align="center">Age (years)</th>
                    <th colspan="2" align="center">Nonanginal chest pain</th>
                    <th colspan="2" align="center">Atypical angina</th>
                    <th colspan="2" align="center">Typical angina</th>
                  </tr>
                  <tr>
                    <th align="center">Male</th>
                    <th align="center">Female</th>
                    <th align="center">Male</th>
                    <th align="center">Female</th>
                    <th align="center">Male</th>
                    <th align="center">Female</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td align="left">35</td>
                    <td align="center">3-35</td>
                    <td align="center">1-19</td>
                    <td align="center">8-59</td>
                    <td align="center">2-39</td>
                    <td align="center">30-88</td>
                    <td align="center">10-78</td>
                  </tr>
                  <tr>
                    <td align="left">45</td>
                    <td align="center">9-47</td>
                    <td align="center">2-22</td>
                    <td align="center">21-70</td>
                    <td align="center">5-43</td>
                    <td align="center">51-92</td>
                    <td align="center">20-79</td>
                  </tr>
                  <tr>
                    <td align="left">55</td>
                    <td align="center">23-59</td>
                    <td align="center">4-25</td>
                    <td align="center">25-79</td>
                    <td align="center">10-47</td>
                    <td align="center">80-95</td>
                    <td align="center">38-82</td>
                  </tr>
                  <tr>
                    <td align="left">65</td>
                    <td align="center">49-69</td>
                    <td align="center">9-29</td>
                    <td align="center">71-86</td>
                    <td align="center">20-51</td>
                    <td align="center">93-97</td>
                    <td align="center">56-84</td>
                  </tr>
                </tbody>
              </table>
            </table-wrap>
            <p>For the assessment of cardiovascular risk, the Brazilian Guidelines for Atherosclerosis Prevention and the V Brazilian Guidelines on Dyslipidemia and Atherosclerosis Prevention were used<xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B05">5</xref>. (Level of recommendation IIa, evidence level B).</p>
          </sec>
        </sec>
        <sec>
          <title>Diagnosis of manifest coronary artery disease</title>
          <sec>
            <title>History, physical examination, differential diagnosis</title>
            <sec>
              <title>Definition of angina</title>
              <p>Angina is a clinical syndrome characterized by pain or discomfort in any of the following regions: chest, epigastrium, mandible, shoulder, dorsum, or upper limbs. It is triggered or aggravated by physical activity or emotional stress and attenuated by nitroglycerin and its derivatives.</p>
            </sec>
            <sec>
              <title>Clinical assessment of patients with chest pain</title>
              <p><bold>a) Clinical history:</bold> Detailed clinical history. Some characteristics should be carefully investigated to determine the probability of the presence of angina:</p>
              <p>quality: constriction, tightness, heaviness, distress, suffocation, discomfort, burning, and stabbing; location: precordium, retrosternal area, shoulder, epigastrium, neck, hemithorax and dorsum; irradiation: upper limbs (right, left, or both), shoulder, mandible, neck, dorsum, and epigastrium; duration: seconds, minutes, hours, or days; triggering factors: exertion, sexual activity, position, eating habits, breathing, emotional component , and spontaneous; relieving factors: rest, sublingual nitrates, analgesic, food, antacids, position, and apnea; associated symptoms: sweating, nausea, vomiting, pallor, dyspnea, hemoptysis, cough, presyncope, and syncope.</p>
              <p>An episode of angina lasts for a few minutes. It is generally triggered by exertion of emotional stress, and relieved by rest. The use of nitroglycerin, such as sublingual nitrate, relieves angina within approximately 1 min. Pain in the chondrosternal joints is rarely of cardiac origin.</p>
              <p>The Canadian Cardiovascular Society (CCS) grading of angina pectoris<xref ref-type="bibr" rid="B06">6</xref> is the most widely used classification of angina (<xref ref-type="table" rid="t02">Chart 1</xref>).</p>
              <table-wrap id="t02">
                <label>Chart 1</label>
                <caption>
                  <title>Canadian Cardiovascular Society grading of angina pectoris</title>
                </caption>
                <table frame="hsides" rules="groups">
                  <tbody>
                    <tr>
                      <td align="left" valign="top">Class I</td>
                      <td align="left" valign="top">Habitual physical activity, such as walking and climbing sairs, does not cause angina. Angina occurs during prolonged or strenuous physical activity.</td>
                    </tr>
                    <tr>
                      <td align="left" valign="top">Class II</td>
                      <td align="left" valign="top">Slight limitation for habitual activities. Angina during walking or climbing stairs rapidly, walking uphill, walking or climbing stairs after meals or in the cold, in the wind or under emotional stress, or within a few hours after waking up. Angina occurs after walking two blocks or climbing more than 1 flight of stairs in normal conditions.</td>
                    </tr>
                    <tr>
                      <td align="left" valign="top">Class III</td>
                      <td align="left" valign="top">Limitation of habitual activities. Angina occurs after walking one block or climbing 1 flight of stairs.</td>
                    </tr>
                    <tr>
                      <td align="left" valign="top">Class IV</td>
                      <td align="left" valign="top">Unable to carry on any habitual physical without discomfort. Angina symptoms may be present at rest.</td>
                    </tr>
                  </tbody>
                </table>
              </table-wrap>
              <p><bold>b) Physical examination:</bold> Physical examination is usually normal in patients with stable angina. However, during an episode of angina, it may provide important evidence about the presence of absence of CAD. When physical examination is performed during an episode of pain, third heart sound (S3), fourth heart sound (S4) or gallop, mitral regurgitation, paradoxical splitting of the second heart sound (S2), and bibasilar crackles are suggestive and predictive indicators of DAC<xref ref-type="bibr" rid="B07">7</xref>. The occurrence of atherosclerosis in other regions, including decreased pulse in lower limbs, arterial hardening, and abdominal aneurysm, increase the likelihood of CAD.</p>
            </sec>
            <sec>
              <title>Differential diagnosis of chest pain: associated conditions, and provoking and relieving factors of angina</title>
              <p>In all patients, especially in those with typical angina, associated (simultaneous) diseases that can precipitate "functional" angina, i.e. myocardial ischemia in the absence of significant anatomic coronary obstruction, should be considered. These diseases generally cause myocardial ischemia either by increasing myocardial oxygen consumption or by decreasing the oxygen supply. An increase in oxygen consumption may be caused by hyperthermia, hyperthyroidism, and cocaine use. Obstructive sleep apnea should be seriously considered in patients with significant nocturnal symptoms.</p>
            </sec>
          </sec>
          <sec>
            <title>Noninvasive tests</title>
            <p>Additional tests in stable angina are based on the probability of CAD. After estimating the probability, it is categorized as low, intermediate, or high according to established values: 10%&#8211;90% in intermediate probability, &lt; 10% in low probability, and &gt; 90% in high probability cases.</p>
            <p>Since overall mortality of patients with stable angina varies from 1.2% to 2.4% per year<xref ref-type="bibr" rid="B08">8</xref>, a diagnostic method that leads to a higher incidence of complications and death would be inappropriate.</p>
            <sec>
              <title>Electrocardiogram</title>
              <p>The test is indicated when a cardiac cause of chest pain is suspected (level of recommendation I, evidence level B).</p>
            </sec>
            <sec>
              <title>Chest radiography</title>
              <p>Chest radiography is indicated for patients with CAD and signs or symptoms of congestive heart failure (level of recommendation I, evidence level B), and patients with signs and symptoms of pulmonary disease (level of recommendation IIa, evidence level B).</p>
            </sec>
            <sec>
              <title>Exercise treadmill test</title>
              <p>The most predictive variables in the diagnosis of coronary obstruction are ST-segment depression &#8805; 1 mm (measured at 0.80 seconds from the J-point), with a horizontal or descending pattern, and presence of anginal pain.</p>
              <sec>
                <title>
                  <underline>Exercise treadmill test for the diagnosis of coronary obstruction</underline>
                </title>
                <list list-type="simple">
                  <list-item>
                    <p>
                      <bold>Level of recommendation I, evidence level B</bold>
                    </p>
                  </list-item>
                  <list-item>
                    <p>1. Intermediate probability</p>
                  </list-item>
                  <list-item>
                    <p>
                      <bold>Level of recommendation IIa, evidence level B</bold>
                    </p>
                  </list-item>
                  <list-item>
                    <p>1. Suspected vasospastic angina.</p>
                  </list-item>
                  <list-item>
                    <p>2. Coronary angiography for assessment of intermediate lesions.</p>
                  </list-item>
                  <list-item>
                    <p>3. Asymptomatic individuals with more than two risk factors.</p>
                  </list-item>
                  <list-item>
                    <p>
                      <bold>Level of recommendation IIb, evidence level B</bold>
                    </p>
                  </list-item>
                  <list-item>
                    <p>1. A high or low pretest probability of coronary obstruction, based on age, sex and symptoms.</p>
                  </list-item>
                  <list-item>
                    <p>2. Risk assessment for noncardiac surgery (in low cardiovascular risk).</p>
                  </list-item>
                </list>
                <p><bold>Level of recommendation III:</bold> abnormalities: pre-excitation syndrome or Wolff-Parkinson-White syndrome, pacemaker rhythm, ST-segment depression &gt;1 mm at rest, and complete left bundle-branch block.</p>
                <sec>
                  <title>Echocardiography</title>
                  <p>Echocardiography may help in the diagnosis<xref ref-type="bibr" rid="B09">9</xref>, by showing reversible and irreversible abnormalities in segmental motion in patients with clinical features of CAD.</p>
                  <p><bold>a) Stress echocardiography in chronic coronary atherosclerotic disease:</bold> the test is used in diagnosis and prognosis, to assess the impact of revascularization therapies and myocardial viability, and to support therapeutic decisions. The test has good accuracy for induced myocardial ischemia in patients with intermediate or high pretest probability, with higher diagnostic sensitivity and specificity as compared with the exercise treadmill test<xref ref-type="bibr" rid="B10">10</xref>.</p>
                  <p><bold>b) Preoperative evaluation:</bold> according to recommendations of the American College of Cardiology/American Heart Association (ACC/AHA) and the European Association of Cardiovascular Imaging (EACVI), dobutamine stress echocardiography has been valuable in preoperative risk stratification in patients with CAD<xref ref-type="bibr" rid="B11">11</xref>.</p>
                </sec>
                <sec>
                  <title>Radioisotopes</title>
                  <p>Aspects of myocardial perfusion, cellular integrity, myocardial metabolism, myocardial contractility, and global or segmental ventricular function are evaluated<xref ref-type="bibr" rid="B12">12</xref>. The radioisotope thallium-201 is less frequently used because of its association with higher radiation, and is indicated for the detection of ischemia concomitant with viable myocardium.</p>
                </sec>
                <sec>
                  <title>Coronary angiography</title>
                  <p>Coronary lesions are significant when one or more epicardial arteries are obstructed, with at least 70% stenosis and/or stenosis greater than 50% of the left main coronary artery. Assessment and measurement of obstructions are performed using coronary angiography (<xref ref-type="table" rid="t03">Chart 2</xref>).</p>
                  <table-wrap id="t03">
                    <label>Chart 2</label>
                    <caption>
                      <title>Recommendations for coronary angiography in patients with coronary artery disease</title>
                    </caption>
                    <table frame="hsides" rules="groups">
                      <tbody>
                        <tr>
                          <td rowspan="4" align="left" valign="top">Class I</td>
                          <td align="left" valign="top">Stable angina (CCS III or IV) despite clinical treatment (B)</td>
                        </tr>
                        <tr>
                          <td align="left" valign="top">High risk in noninvasive tests, regardless of angina (B)</td>
                        </tr>
                        <tr>
                          <td align="left" valign="top">Angina and cardiac arrest or severe ventricular arrhythmia survivors (B)</td>
                        </tr>
                        <tr>
                          <td align="left" valign="top">Angina and symptoms/signs of congestive heart failure (C)</td>
                        </tr>
                        <tr>
                          <td rowspan="4" align="left" valign="top">Class IIa</td>
                          <td align="left" valign="top">Patients with uncertain diagnosis after noninvasive tests, when the benefits of an accurate diagnosis outweigh the risks and costs of coronary angiography (C)</td>
                        </tr>
                        <tr>
                          <td align="left" valign="top">Unable to undergo noninvasive tests due to physical disability, illness, or obesity (C)</td>
                        </tr>
                        <tr>
                          <td align="left" valign="top">High-risk jobs that require an accurate diagnosis (C)</td>
                        </tr>
                        <tr>
                          <td align="left" valign="top">Patients with uncertain prognostic information after noninvasive tests (C)</td>
                        </tr>
                        <tr>
                          <td align="left" valign="top">Class IIb</td>
                          <td align="left" valign="top">Multiple hospitalizations for chest pain, when a definitive diagnosis is considered necessary (C)</td>
                        </tr>
                        <tr>
                          <td rowspan="3" align="left" valign="top">Class III</td>
                          <td align="left" valign="top">Significant comorbidities, when the risks of angiography outweigh the benefits of the procedure (C)</td>
                        </tr>
                        <tr>
                          <td align="left" valign="top">Stable angina (CCS I or II) that responds to drug treatment and no evidence of ischemia in noninvasive tests (C)</td>
                        </tr>
                        <tr>
                          <td align="left" valign="top">Preference to avoid revascularization (C)</td>
                        </tr>
                      </tbody>
                    </table>
                    <table-wrap-foot>
                      <fn id="TFN01">
                        <p>CCS: Canadian Cardiovascular Society.</p>
                      </fn>
                    </table-wrap-foot>
                  </table-wrap>
                </sec>
                <sec>
                  <title>Cardiac computed tomography</title>
                  <p>There are two main modes of examinations using cardiac computed tomography that use different techniques and provide different information: the calcium score and coronary computed tomography angiography.</p>
                  <p>
                    <bold>a) Calcium score</bold>
                  </p>
                  <p>Quantification of coronary artery calcification using calcium score correlates with the atheroscleroctic load<xref ref-type="bibr" rid="B13">13</xref>.</p>
                  <p>
                    <bold>Level of recommendation I, evidence level A</bold>
                  </p>
                  <p>Asymptomatic individuals at intermediate risk using the overall risk score.</p>
                  <p>
                    <bold>Level of recommendation IIa, evidence level B</bold>
                  </p>
                  <p>Asymptomatic individuals at low risk using the overall risk score and family history of early CAD.</p>
                  <list list-type="order">
                    <title>Level of recommendation IIIa, evidence level B</title>
                    <list-item>
                      <p>Asymptomatic patients at high risk of CAD or with known CAD.</p>
                    </list-item>
                    <list-item>
                      <p>Follow-up of coronary calcification progression.</p>
                    </list-item>
                    <list-item>
                      <p>Symptomatic patients.</p>
                    </list-item>
                  </list>
                  <p>
                    <bold>b) Coronary computed tomography angiography</bold>
                  </p>
                  <p>Coronary computed tomography angiography enables the noninvasive evaluation of the lumen of coronary arteries<xref ref-type="bibr" rid="B14">14</xref>.</p>
                  <p>The test is clinically indicated for symptomatic patients with conflicting results between ischemia and clinical tests.</p>
                  <p>
                    <bold>Level of recommendation IIa, evidence level A</bold>
                  </p>
                  <list list-type="simple">
                    <list-item>
                      <p>Suspected chronic CAD using:</p>
                    </list-item>
                    <list-item>
                      <p>a) Previous conflicting or inconclusive ischemia tests;</p>
                    </list-item>
                    <list-item>
                      <p>b) Continuous symptoms and ischemia tests with normal or inconclusive results.</p>
                    </list-item>
                  </list>
                  <p>
                    <bold>Level of recommendation IIa, evidence level B</bold>
                  </p>
                  <list list-type="order">
                    <list-item>
                      <p>To assess the patency of grafts for myocardial revascularization in symptomatic individuals with pretest probability.</p>
                    </list-item>
                  </list>
                  <p>
                    <bold>Level of recommendation IIb, evidence level B</bold>
                  </p>
                  <list list-type="order">
                    <list-item>
                      <p>Symptomatic individuals with intermediate probability of CAD and positive ischemia tests.</p>
                    </list-item>
                    <list-item>
                      <p>Symptomatic individuals with low probability of CAD and negative ischemia tests.</p>
                    </list-item>
                    <list-item>
                      <p>Assessment of in-stent restenosis in symptomatic individuals with intermediate pretest probability.</p>
                    </list-item>
                  </list>
                  <p>
                    <bold>Level of recommendation III, evidence level B</bold>
                  </p>
                  <list list-type="order">
                    <list-item>
                      <p>Symptomatic individuals with high probability of CAD.</p>
                    </list-item>
                    <list-item>
                      <p>Initial evaluation of CAD in asymptomatic individuals, able to exercise and with interpretable electrocardiogram.</p>
                    </list-item>
                    <list-item>
                      <p>Follow-up of coronary atheroscleroctic lesions in asymptomatic individuals.</p>
                    </list-item>
                  </list>
                </sec>
                <sec>
                  <title>Cardiovascular magnetic resonance imaging</title>
                  <p>Magnetic resonance imaging is an excellent diagnostic method; it allows the assessment of cardiac and vascular anatomy, ventricular function, myocardial perfusion, and tissue characterization in an accurate, reproducible manner, in a single test<xref ref-type="bibr" rid="B15">15</xref>.</p>
                  <p>
                    <bold>a) Myocardial ischemia</bold>
                  </p>
                  <p>The protocols for the investigation of ischemia by magnetic resonance with myocardial perfusion are similar to those used in scintigraphy.</p>
                  <p>
                    <bold>b) Delayed enhancement</bold>
                  </p>
                  <p>The diagnosis and characterization of areas of myocardial infarction/necrosis/fibrosis using CMR is based on the delayed enhancement technique<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B18">18</xref>.</p>
                  <p>c) Coronary magnetic resonance angiography</p>
                  <p>The clinical use of the test has been focused on the assessment of congenital anomalies and the origin and course of the coronary arteries<xref ref-type="bibr" rid="B19">19</xref>.</p>
                </sec>
              </sec>
              <sec>
                <title>
                  <underline>Recommendations for magnetic resonance imaging</underline>
                </title>
                <sec>
                  <title>Level of recommendation I, evidence level A</title>
                  <p>Evaluation of the global (left and right) ventricular function, volume, and mass</p>
                  <p>Detection of ischemia:</p>
                  <list list-type="bullet">
                    <list-item>
                      <p>Assessment of myocardial perfusion under stress using vasodilators.</p>
                    </list-item>
                    <list-item>
                      <p>Assessment of ventricular contractility using dobutamine stress magnetic resonance.</p>
                    </list-item>
                    <list-item>
                      <p>Detection and quantification of myocardial fibrosis and infarction.</p>
                    </list-item>
                    <list-item>
                      <p>Assessment of myocardial viability.</p>
                    </list-item>
                  </list>
                </sec>
                <sec>
                  <title>Level of recommendation I, evidence level B</title>
                  <p>Differentiation between ischemic and nonischemic cardiopahty</p>
                  <list list-type="bullet">
                    <list-item>
                      <p>Coronary magnetic resonance angiography:</p>
                    </list-item>
                    <list-item>
                      <p>Assessment of congenital anomalies.</p>
                    </list-item>
                  </list>
                </sec>
              </sec>
            </sec>
          </sec>
        </sec>
        <sec>
          <title>Cardiovascular risk stratification in CAD</title>
          <p>The strategies and methods used in the diagnosis of CAD also provide information on disease severity, with implications for complementary invasive methods, including coronary angiography, and therapeutic decision-making.</p>
          <sec>
            <title>Exercise treadmill test for the prognosis of coronary atherosclerosis</title>
            <p>
              <bold>Level of recommendation I, evidence level B</bold>
            </p>
            <p>Patients with intermediate or high probability of CAD after initial evaluation; patients showing changes in symptoms.</p>
            <p>
              <bold>Level of recommendation IIb, evidence level B</bold>
            </p>
            <p>Patients with pre-excitation, ST-segment depression &gt; 1 mm in echocardiogram at rest, pacemaker rhythm, and complete left bundle-branch block.</p>
            <p>
              <bold>Level of recommendation IIa, evidence level C</bold>
            </p>
            <p>Revascularized patients with symptoms suggestive of ischemia.</p>
            <p>
              <bold>Level of recommendation III, evidence level C</bold>
            </p>
            <p>Patients with severe comorbidities.</p>
            <p>In patients with CAD who are able to reach stage 3 of the Bruce protocol, the annual mortality rate is approximately 1%, whereas in those unable to exceed 5 METs, the annual mortality rate is approximately 5%<xref ref-type="bibr" rid="B20">20</xref>.</p>
            <p>Other high-risk variables include ST-segment depression in multiple leads, persistent ST-segment depression in recovery phase &gt; 5 min, inadequate chronotropic response, fall in systolic blood pressure during physical exertion or a flat curve, and severe ventricular arrhythmia at low level of exercise in the presence of ST-segment depression or anginal pain.</p>
            <sec>
              <title>
                <underline>Stress echocardiography</underline>
              </title>
              <p>Echocardiography for CAD prognosis takes into account mainly the left ventricle function, and the presence or absence of myocardial ischemia induced by physical or pharmacological stress on echocardiography. In asymptomatic patients who have successfully undergone coronary artery bypass graft surgery (CABG), routine evaluation using stress echocardiography is not indicated. Other important variables for risk stratification include pulmonary uptake of thallium in myocardial perfusion scintigraphy, and the transient increase in the left ventricle.</p>
            </sec>
          </sec>
        </sec>
        <sec>
          <title>Strategies for the diagnosis and stratification of coronary artery disease</title>
          <p>The prognosis of CAD may also be based on the direct anatomical visualization of the coronary lesion by coronary angiography. Normal functional testing, performed with appropriate stress protocol yields the same prognosis as compared with the standard coronary angiography test.</p>
        </sec>
      </sec>
    </sec>
    <sec>
      <title>Part II &#8211; Drug Treatment</title>
      <p>The main objectives of the treatment of CAD are to prevent myocardial infarction and decrease mortality, and to reduce symptoms and the incidence of myocardial ischemia, providing a better quality of life.</p>
      <sec>
        <title>Drug treatments to reduce the risk of myocardial infarction and mortality</title>
        <sec>
          <title>Antiplatelet drugs</title>
          <p><bold>a) Acetylsalicylic acid (ASA):</bold> Level of recommendation I, evidence level A.</p>
          <p>b) Thienopyridine derivatives:</p>
          <p><bold>Clopidogrel:</bold> Level of recommendation I, evidence level B. Indicated when aspirin is absolutely contraindicated, and associated with aspirin after stent implant for at least 30 days.</p>
          <p><bold>Ticlopidine:</bold> Level of recommendation IIa, evidence level B. Indicated when aspirin is absolutely contraindicated, and associated with aspirin after stent implant for at least 30 days.</p>
          <p><bold>c) Dipyridamole:</bold> Level of recommendation III, evidence level B.</p>
          <p><bold>d) Anticoagulants:</bold> should be used in combination with aspirin in case of high risk of thrombosis, especially after myocardial infarction. Level of recommendation I, evidence level A.</p>
          <p>As an alternative to aspirin intolerance: Level of recommendation IIa, evidence level A.</p>
          <p>For specific situations and after implantation of antiproliferative drugs-coated stent, follow the Brazilian Guidelines of Antiplatelet Agents and Anticoagulants in Cardiology.</p>
        </sec>
        <sec>
          <title>Secondary prevention: Hypolipidemic agent</title>
          <p>Lifestyle change (LC) is recommended for all patients with CAD (<xref ref-type="table" rid="t04">Chart 3</xref>).</p>
          <table-wrap id="t04">
            <label>Chart 3</label>
            <caption>
              <title>Recommendations for drug therapy in dyslipidemias</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th align="left">Indications</th>
                  <th align="center">Class-level of evidence</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Statins are first choice treatment in primary and secondary prevention</td>
                  <td align="center">I-A</td>
                </tr>
                <tr>
                  <td align="left">Fibrate monotherapy or in combination with statins to prevent microvascular diseases in type 2 diabetes patients</td>
                  <td align="center">I-A</td>
                </tr>
                <tr>
                  <td align="left">Associations of ezetimibe or resins with statins when LDL-C target levels are not achieved</td>
                  <td align="center">IIa-C</td>
                </tr>
                <tr>
                  <td align="left">Association of niacin with statins</td>
                  <td align="center">III-A</td>
                </tr>
                <tr>
                  <td align="left">Omega-3 fatty acids for cardiovascular prevention</td>
                  <td align="center">IIII-A</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN02">
                <p>Source: Brazilian guidelines for cardiovascular disease prevention<xref ref-type="bibr" rid="B10">10</xref>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Blockade of the renin&#8211;angiotensin system</title>
          <p><bold>a) ACE inhibitors:</bold> the benefits of ACE inhibitors in the treatment of CAD have been shown in clinical trials involving asymptomatic patients with reduced ejection fraction<xref ref-type="bibr" rid="B21">21</xref> and patients with ventricular dysfunction after acute myocardial infarction<xref ref-type="bibr" rid="B21">21</xref><sup>,</sup><xref ref-type="bibr" rid="B22">22</xref>. They should be used routinely for ventricular dysfunction, and/or heart failure, and/or diabetes mellitus management<xref ref-type="bibr" rid="B23">23</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref>. Level of recommendation I, evidence level A.</p>
          <p>It should be used routinely in all patients with CAD: Level of recommendation IIa, evidence level A.</p>
          <p><bold>b) Angiotensin receptor blockers:</bold> alternative therapy for patients intolerant to ACE inhibitors, since no study has been conducted on the use of this group of drugs in stable coronary disease. In other situations, angiotensin receptor blockers have provided no additional benefits over those of ACE inhibitors, which can decrease the incidence of infarction.</p>
        </sec>
      </sec>
      <sec>
        <title>Treatment to reduce symptoms and myocardial ischemia</title>
        <p><bold>a) Beta-blockers:</bold> beta-blockers are drugs of choice, to be administered alone or in combination with other antianginal drugs. Indicated as first-line agents in patients with stable angina without previous myocardial infarction and/or left ventricle dysfunction<xref ref-type="bibr" rid="B25">25</xref>. Level of recommendation I, evidence level B.</p>
        <list list-type="simple">
          <list-item>
            <p>First-line agents in patients with stable angina within 2 years of myocardial infarction and/or left ventricle. Level of recommendation III, evidence level C.</p>
          </list-item>
          <list-item>
            <p>For symptomatic relief in patients with vasospastic angina: Level of recommendation III, evidence level C.</p>
          </list-item>
        </list>
        <p><bold>b) Calcium-channel blockers:</bold> heterogeneous group of drugs with pharmacological effects that include smooth muscle relaxation, afterload reduction, and negative inotropic effects (some formulations). On the other hand, they are contraindicated in case of ventricular dysfunction (verapamil and diltiazem)<xref ref-type="bibr" rid="B26">26</xref>.</p>
        <list list-type="simple">
          <list-item>
            <p>&#8211; First-line agents for symptomatic relief in patients with vasospastic angina. Level of recommendation IIa, evidence level B.</p>
          </list-item>
          <list-item>
            <p>&#8211; In symptomatic patients with stable angina on beta-blockers (dihydropyridines). Level of recommendation I, evidence level B.</p>
          </list-item>
          <list-item>
            <p>&#8211; In symptomatic patients with stable angina on beta-blockers (verapamil or diltiazem). Level of recommendation III, evidence level B.</p>
          </list-item>
          <list-item>
            <p>&#8211; In patients with stable angina and contraindications to beta-blockers (preferably verapamil or diltiazem). Level of recommendation I, evidence level B.</p>
          </list-item>
          <list-item>
            <p>&#8211; In symptomatic patients with stable angina (fast-acting ihydropyridines). Level of recommendation III, evidence level B.</p>
          </list-item>
        </list>
        <p>
          <bold>c) Nitrates:</bold>
        </p>
        <list list-type="simple">
          <list-item>
            <p>&#8211; <bold>Fast-acting nitrates:</bold> for symptomatic relief of acute angina. Level of recommendation I, evidence level B.</p>
          </list-item>
          <list-item>
            <p>&#8211; <bold>Long-acting nitrates:</bold> continuous use of long-acting nitrates leads to drug tolerance.</p>
          </list-item>
          <list-item>
            <p>&#8211; First-line agents in patients with stable angina. Level of recommendation III, evidence level C.</p>
          </list-item>
          <list-item>
            <p>&#8211; Third-line agents in stable angina patients who still have symptoms even after using other antianginal agents associated. Level of recommendation IIa, evidence level B.</p>
          </list-item>
          <list-item>
            <p>&#8211; For symptomatic relief in patients with vasospastic angina after using calcium-channel blockers. Level of recommendation IIa, evidence level B.</p>
          </list-item>
        </list>
        <p><bold>d) Trimetazidine:</bold> drug with metabolic and anti-ischemic effects and no effect on cardiovascular hemodynamics<xref ref-type="bibr" rid="B27">27</xref>.</p>
        <list list-type="simple">
          <list-item>
            <p>&#8211; In symptomatic patients with stable angina on beta-blockers alone or in combination with other antianginal agents. Level of recommendation IIa, evidence level B.</p>
          </list-item>
          <list-item>
            <p>&#8211; In patients with stable angina and left ventricle dysfunction associated with optimized medical therapy. Level of recommendation IIa, evidence level B.</p>
          </list-item>
          <list-item>
            <p>&#8211; In patients with stable angina during myocardial revascularization procedures (percutaneous or surgical). Level of recommendation IIa, evidence level B.</p>
          </list-item>
        </list>
        <p><bold>e) Ivabradine:</bold> a specific sinus node I<sub><italic>f</italic></sub>current i inhibitor, which specifically decreases the heart rate<xref ref-type="bibr" rid="B28">28</xref>.</p>
        <list list-type="simple">
          <list-item>
            <p>&#8211; In symptomatic patients with stable angina on beta-blockers alone or with other antianginal agents, and heart rate &gt; 70 bpm. Level of recommendation IIa, evidence level B.</p>
          </list-item>
          <list-item>
            <p>&#8211; In symptomatic patients with stable angina who are intolerant to beta-blockers alone or with other antianginal agents. Level of recommendation IIb, evidence level B.</p>
          </list-item>
          <list-item>
            <p>&#8211; In patients with stable angina, left ventricle dysfunction (LVEF &lt; 40%) and heart rate &#8805; 70 bpm under optimized medical therapy. Level of recommendation IIa, evidence level B.</p>
          </list-item>
        </list>
        <p><bold>f) Ranolazine:</bold> piperazine derivative. Similar to trimetazidine, it protects patients from ischemia by increasing glucose metabolism and decreasing fatty acids oxidation. However, its major effect appears to be the inhibition of late sodium current<xref ref-type="bibr" rid="B29">29</xref>.</p>
        <p><xref ref-type="fig" rid="f01">Figures 1</xref> and <xref ref-type="fig" rid="f02">2</xref> depict algorithms that facilitate understanding of drug therapy options in stable CAD.</p>
        <fig id="f01">
          <label>Figure 1</label>
          <caption>
            <title>Algorithm for drug treatment of stable angina with antianginal drugs to relieve symptoms and improve quality of life. Details, levels of recommendation and evidence level: see the corresponding text.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-105-04-0328-50136-gf01.jpg"/></fig>
        <fig id="f02">
          <label>Figure 2</label>
          <caption>
            <title>Algorithm for reduction of cardiovascular events in the presence of left ventricular dysfunction. Details, levels of recommendation and evidence level: see the corresponding text. ASA: Acetylsalicylic acid; AH: Arterial hypertension; ACE inhibitors: Angiotensin-converting enzyme inhibitors; ARB: Angiotensin receptor blocker I; AP: Arterial pressure; HR: Heart rate.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-105-04-0328-50136-gf02.jpg"/></fig>
      </sec>
    </sec>
    <sec>
      <title>Part III &#8211; Treatment with invasive measures</title>
      <sec>
        <title>Treatment with invasive measures</title>
        <sec>
          <title>Direct surgical revascularization</title>
          <p>The Guidelines on Myocardial Revascularization<xref ref-type="bibr" rid="B30">30</xref> cover the procedure techniques, alternatives, and current practices. They also briefly review classic studies, comparing surgical treatment strategies with clinical treatment and percutaneous coronary intervention.</p>
          <sec>
            <title>Main indications for direct revascularization</title>
            <p>
              <bold>Level of recommendation I</bold>
            </p>
            <p>Left main coronary artery stenosis &#8805; 50% or equivalent conditions (left descending anterior and circumflex arteries in the ostium, or before the exit of important branches). Evidence level A.</p>
            <p>Proximal stenosis (&gt; 70%) in the three main arteries with or without involvement of proximal left anterior descending artery, especially in patients with ejection fraction &lt; 50% or functional evidence of moderate to severe ischemia. Evidence level B.</p>
            <p>Stenosis in two main vessels, with proximal left anterior descending artery lesion in patients with ejection fraction &lt; 50% or functional evidence of moderate to severe ischemia. Evidence level B.</p>
            <p>
              <bold>Level of recommendation IIa</bold>
            </p>
            <p>Left internal mammary artery graft in patients with significant stenosis (&gt; 70%) in proximal left anterior descending artery and evidence of extensive ischemia, aiming to improve survival. Evidence level B.</p>
            <p>Coronary artery by-pass surgery instead of percutaneous coronary intervention in patients with multivessel CAD and diabetes mellitus, particularly in those who underwent internal mammary artery grafting with revascularization to the left anterior descending artery. Evidence level B.</p>
            <p>
              <bold>Level of recommendation III</bold>
            </p>
            <p>Asymptomatic patients with normal ventricular function, without extensive areas of ischemia or involvement of the left anterior descending artery. Evidence level C.</p>
            <p>Asymptomatic patients without significant anatomical lesions (&lt; 70%, or &lt; 50% of the left main coronary artery) or functional lesions (e.g., fractional flow reserve &gt; 0.8 or mild ischemia in noninvasive tests). Evidence level C.</p>
            <p>Involvement of one or two arteries, except for the proximal left anterior descending artery, with no evidence of relevant ischemia in functional tests, and presence of perfusion in small areas of viable myocardium. Evidence level B.</p>
            <p>Moderate lesions (between 50% and 60%) except in left main coronary artery, without moderate ischemia in functional tests.</p>
            <p>Insignificant lesions (&lt; 50%).</p>
          </sec>
          <sec>
            <title>The "Heart Team" concept for myocardial revascularization</title>
            <sec>
              <title>
                <underline>Class I</underline>
              </title>
              <p>A team made up of clinical cardiologists, cardiac surgeons and interventional cardiologists is recommended to individualize the indication for the treatment of left main coronary artery lesions or complex CAD. Evidence level C<xref ref-type="bibr" rid="B31">31</xref>.</p>
            </sec>
          </sec>
        </sec>
        <sec>
          <title>Catheter-based revascularization: clinical indications</title>
          <sec>
            <title>Revascularization vs. drug treatment (<xref ref-type="fig" rid="f03">Figure 3</xref>)</title>
            <fig id="f03">
              <label>Figure 3</label>
              <caption>
                <title>Percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) in stable coronary atheroscleroctic disease without involvement of left main coronary artery. a&#8805; 50% stenosis and confirmation of ischemia, lesion &gt; 90% confirmed by two physicians or fractional flow reserve of 0.80; bCABG is the preferred option in most patients, unless in case of comorbidities or other particularities that require discussion with the Heart Team. Adapted from: 2010 Guidelines on myocardial revascularization of the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-105-04-0328-50136-gf03.jpg"/></fig>
            <sec>
              <title>Percutaneous coronary intervention vs. clinical treatment</title>
              <p>To date, no study has demonstrated that percutaneous coronary intervention in patients with CAD improves survival rates<xref ref-type="bibr" rid="B32">32</xref>.</p>
            </sec>
            <sec>
              <title>Appropriate use of revascularization</title>
              <sec>
                <title>Patients with three-vessel disease</title>
                <p>The coronary artery bypass surgery is the preferred strategy for three-vessel disease patients with increased age, low ejection fraction, renal dysfunction, peripheral vascular disease, diabetes mellitus, or Syntax score &gt; 22.</p>
              </sec>
            </sec>
          </sec>
        </sec>
      </sec>
      <sec>
        <title>Special situations</title>
        <sec>
          <title>Patients with diabetes mellitus</title>
          <p>Diabetes mellitus is an increasingly prevalent condition associated with increased risk of cardiovascular complications, especially late mortality.</p>
          <sec>
            <title>Indications for myocardial revascularization</title>
            <sec>
              <title>Comparison of revascularization strategies in diabetic patients with multi-vessel CAD</title>
              <p>Sensitivity analysis showed that the superiority of coronary artery bypass surgery was more evident in individuals with high Syntax score (&gt; 33), with no significant difference between the low score and intermediate score groups<xref ref-type="bibr" rid="B33">33</xref>.</p>
            </sec>
            <sec>
              <title>Aspects of percutaneous coronary intervention in diabetes mellitus patients</title>
              <p>Drug-eluting stents are recommended to reduce restenosis and the need of a new target vessel revascularization<xref ref-type="bibr" rid="B34">34</xref><sup>,</sup><xref ref-type="bibr" rid="B35">35</xref>.</p>
              <p>The dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is an essential component of drug regiments for perioperative and postoperative periods. Patients who receive drug-eluting stents should use the therapy for 12 months, and those who receive non-drug-eluting stents should use it for 1 month.</p>
            </sec>
          </sec>
          <sec>
            <title>Patients with previous revascularization</title>
            <p>The main indications for revascularization are persistence of symptoms, despite optimized medical therapy and/or prognosis.</p>
          </sec>
        </sec>
      </sec>
    </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 study is not associated with any thesis or dissertation work.</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>References</title>
      <ref id="B01">
        <label>1</label>
        <mixed-citation>Mansur AP, Favarato D. Mortality due to cardiovascular diseases in Brazil and in the metropolitan region of S&#227;o Paulo: a 2011 update. Arq Bras Cardiol. 2012;99(2):755-61.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Mansur</surname>
              <given-names>AP</given-names>
            </name>
            <name>
              <surname>Favarato</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>Mortality due to cardiovascular diseases in Brazil and in the metropolitan region of S&#227;o Paulo: a 2011 update</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2012</year>
          <volume>99</volume>
          <issue>2</issue>
          <fpage>755</fpage>
          <lpage>761</lpage>
        </element-citation>
      </ref>
      <ref id="B02">
        <label>2</label>
        <mixed-citation>Diamond GA, Forrester JS. Analysis of probability as an aid the clinical diagnosis of coronary-artery disease. N Engl J Med. 1979;300(24):1350-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Diamond</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Forrester</surname>
              <given-names>JS</given-names>
            </name>
          </person-group>
          <article-title>Analysis of probability as an aid the clinical diagnosis of coronary-artery disease</article-title>
          <source>N Engl J Med</source>
          <year>1979</year>
          <volume>300</volume>
          <issue>24</issue>
          <fpage>1350</fpage>
          <lpage>1358</lpage>
        </element-citation>
      </ref>
      <ref id="B03">
        <label>3</label>
        <mixed-citation>Chaitman BR, Bourassa MG, Davis K, Rogers WJ, Tyras DH, Berger R, et al. Angiographic prevalence of high-risk coronary artery disease in patient subsets (CASS). Circulation. 1981;64(2):360-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chaitman</surname>
              <given-names>BR</given-names>
            </name>
            <name>
              <surname>Bourassa</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Davis</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Rogers</surname>
              <given-names>WJ</given-names>
            </name>
            <name>
              <surname>Tyras</surname>
              <given-names>DH</given-names>
            </name>
            <name>
              <surname>Berger</surname>
              <given-names>R</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Angiographic prevalence of high-risk coronary artery disease in patient subsets (CASS)</article-title>
          <source>Circulation</source>
          <year>1981</year>
          <volume>64</volume>
          <issue>2</issue>
          <fpage>360</fpage>
          <lpage>367</lpage>
        </element-citation>
      </ref>
      <ref id="B04">
        <label>4</label>
        <mixed-citation>Sim&#227;o AF, Pr&#233;coma DB, Andrade JP, Correa Filho H, Saraiva JF, Oliveira GM, et al; Sociedade Brasileira de Cardiologia. [I Brazilian Guidelines for cardiovascular prevention]. Arq Bras Cardiol. 2013;101(6 Suppl. 2):1-63.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sim&#227;o</surname>
              <given-names>AF</given-names>
            </name>
            <name>
              <surname>Pr&#233;coma</surname>
              <given-names>DB</given-names>
            </name>
            <name>
              <surname>Andrade</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Correa</surname>
              <given-names>H</given-names>
              <suffix>Filho</suffix>
            </name>
            <name>
              <surname>Saraiva</surname>
              <given-names>JF</given-names>
            </name>
            <name>
              <surname>Oliveira</surname>
              <given-names>GM</given-names>
            </name>
            <etal/>
            <collab>Sociedade Brasileira de Cardiologia</collab>
          </person-group>
          <article-title>I Brazilian Guidelines for cardiovascular prevention</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2013</year>
          <volume>101</volume>
          <issue>6</issue>
          <supplement>Suppl. 2</supplement>
          <fpage>1</fpage>
          <lpage>63</lpage>
        </element-citation>
      </ref>
      <ref id="B05">
        <label>5</label>
        <mixed-citation>Xavier HT, Izar MC, Faria Neto JR, Assad MH, Rocha VZ, Sposito AC, et al; Sociedade Brasileira de Cardiologia. V Diretriz brasileira de dislipidemias e preven&#231;&#227;o da aterosclerose. Arq Bras Cardiol. 2013;101(4 supl. 1):1-36.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Xavier</surname>
              <given-names>HT</given-names>
            </name>
            <name>
              <surname>Izar</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Faria</surname>
              <given-names>JR</given-names>
              <suffix>Neto</suffix>
            </name>
            <name>
              <surname>Assad</surname>
              <given-names>MH</given-names>
            </name>
            <name>
              <surname>Rocha</surname>
              <given-names>VZ</given-names>
            </name>
            <name>
              <surname>Sposito</surname>
              <given-names>AC</given-names>
            </name>
            <etal/>
            <collab>Sociedade Brasileira de Cardiologia</collab>
          </person-group>
          <article-title>V Diretriz brasileira de dislipidemias e preven&#231;&#227;o da aterosclerose</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2013</year>
          <volume>101</volume>
          <issue>4</issue>
          <supplement>supl. 1</supplement>
          <fpage>1</fpage>
          <lpage>36</lpage>
        </element-citation>
      </ref>
      <ref id="B06">
        <label>6</label>
        <mixed-citation>Campeau L. The Canadian Cardiovascular Society grading of angina pectoris revisited 30 years later. Can J Cardiol. 2002;18(4):371-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Campeau</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>The Canadian Cardiovascular Society grading of angina pectoris revisited 30 years later</article-title>
          <source>Can J Cardiol</source>
          <year>2002</year>
          <volume>18</volume>
          <issue>4</issue>
          <fpage>371</fpage>
          <lpage>379</lpage>
        </element-citation>
      </ref>
      <ref id="B07">
        <label>7</label>
        <mixed-citation>Levine HJ. Difficult problems in the diagnosis of chest pain. Am Heart J. 1980;100(1):108-18.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Levine</surname>
              <given-names>HJ</given-names>
            </name>
          </person-group>
          <article-title>Difficult problems in the diagnosis of chest pain</article-title>
          <source>Am Heart J</source>
          <year>1980</year>
          <volume>100</volume>
          <issue>1</issue>
          <fpage>108</fpage>
          <lpage>118</lpage>
        </element-citation>
      </ref>
      <ref id="B08">
        <label>8</label>
        <mixed-citation>Steg PG, Greenlaw N, Tardif JC, Tendera M, Ford I, Kaab S, et al. Women and men with stable coronary artery disease have similar clinical outcomes: insights from the international prospective CLARIFY registry. Eur Heart J. 2012;33(22):2831-40.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Steg</surname>
              <given-names>PG</given-names>
            </name>
            <name>
              <surname>Greenlaw</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Tardif</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Tendera</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Ford</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Kaab</surname>
              <given-names>S</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Women and men with stable coronary artery disease have similar clinical outcomes: insights from the international prospective CLARIFY registry</article-title>
          <source>Eur Heart J</source>
          <year>2012</year>
          <volume>33</volume>
          <issue>22</issue>
          <fpage>2831</fpage>
          <lpage>2840</lpage>
        </element-citation>
      </ref>
      <ref id="B09">
        <label>9</label>
        <mixed-citation>Barbosa MM, Nunes MC, Campos Filho O, Camarozano A, Rabischoffsky A, Maciel BC, et al; Sociedade Brasileira de Cardiologia. Diretrizes das indica&#231;&#245;es da ecocardiografia. Arq Bras Cardiol. 2009;93(6 supl.3):e265-302.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Barbosa</surname>
              <given-names>MM</given-names>
            </name>
            <name>
              <surname>Nunes</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Campos</surname>
              <given-names>O</given-names>
              <suffix>Filho</suffix>
            </name>
            <name>
              <surname>Camarozano</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Rabischoffsky</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Maciel</surname>
              <given-names>BC</given-names>
            </name>
            <etal/>
            <collab>Sociedade Brasileira de Cardiologia</collab>
          </person-group>
          <article-title>Diretrizes das indica&#231;&#245;es da ecocardiografia</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2009</year>
          <volume>93</volume>
          <issue>6</issue>
          <supplement>supl.3</supplement>
          <fpage>e265</fpage>
          <lpage>e302</lpage>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>Mathias W Jr, Arruda AL, Andrade JL, Campos O, Porter TR. Endocardial border delineation during dobutamine infusion through use of contrast echocardiography. Echocardiography. 2002;19(2):109-14.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Mathias</surname>
              <given-names>W Jr</given-names>
            </name>
            <name>
              <surname>Arruda</surname>
              <given-names>AL</given-names>
            </name>
            <name>
              <surname>Andrade</surname>
              <given-names>JL</given-names>
            </name>
            <name>
              <surname>Campos</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Porter</surname>
              <given-names>TR</given-names>
            </name>
          </person-group>
          <article-title>Endocardial border delineation during dobutamine infusion through use of contrast echocardiography</article-title>
          <source>Echocardiography</source>
          <year>2002</year>
          <volume>19</volume>
          <issue>2</issue>
          <fpage>109</fpage>
          <lpage>114</lpage>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, et al; European Association of Echocardiography. Stress echocardiography expert consensus statement. European Association of Echocardiography (EAE). Eur J Echocardiogr. 2008;9(4):415-37.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sicari</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Nihoyannopoulos</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Evangelista</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Kasprzak</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Lancellotti</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Poldermans</surname>
              <given-names>D</given-names>
            </name>
            <etal/>
            <collab>European Association of Echocardiography</collab>
          </person-group>
          <article-title>Stress echocardiography expert consensus statement. European Association of Echocardiography (EAE)</article-title>
          <source>Eur J Echocardiogr</source>
          <year>2008</year>
          <volume>9</volume>
          <issue>4</issue>
          <fpage>415</fpage>
          <lpage>437</lpage>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>Marcassa C, Bax JJ, Bengel F, Hesse B, Petersen CL, Reyes E, et al. Clinical value, cost effectiveness, and safety of myocardial perfusion scintigraphy: a position statement. Eur Heart J. 2008;29(4):557-63.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marcassa</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Bax</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>Bengel</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Hesse</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Petersen</surname>
              <given-names>CL</given-names>
            </name>
            <name>
              <surname>Reyes</surname>
              <given-names>E</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Clinical value, cost effectiveness, and safety of myocardial perfusion scintigraphy: a position statement</article-title>
          <source>Eur Heart J</source>
          <year>2008</year>
          <volume>29</volume>
          <issue>4</issue>
          <fpage>557</fpage>
          <lpage>563</lpage>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med. 2008;358(13):1336-45.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Detrano</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Guerci</surname>
              <given-names>AD</given-names>
            </name>
            <name>
              <surname>Carr</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>Bild</surname>
              <given-names>DE</given-names>
            </name>
            <name>
              <surname>Burke</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Folsom</surname>
              <given-names>AR</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Coronary calcium as a predictor of coronary events in four racial or ethnic groups</article-title>
          <source>N Engl J Med</source>
          <year>2008</year>
          <volume>358</volume>
          <issue>13</issue>
          <fpage>1336</fpage>
          <lpage>1345</lpage>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008;52(21):1724-32.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Budoff</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Dowe</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Jollis</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Gitter</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Sutherland</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Halamert</surname>
              <given-names>E</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2008</year>
          <volume>52</volume>
          <issue>21</issue>
          <fpage>1724</fpage>
          <lpage>1732</lpage>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>Hundley WG, Bluemke DA, Finn JP, Flamm SD, Fogel MA, Friedrich MG, et al; American College of Cardiology Foundation Task Force on Expert Consensus Documents.ACCF/ACR/AHA/NASCI/SCMR 2010 expert consensus document on cardiovascular magnetic resonance: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Circulation. 2010;121(22):2462-508.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hundley</surname>
              <given-names>WG</given-names>
            </name>
            <name>
              <surname>Bluemke</surname>
              <given-names>DA</given-names>
            </name>
            <name>
              <surname>Finn</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Flamm</surname>
              <given-names>SD</given-names>
            </name>
            <name>
              <surname>Fogel</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Friedrich</surname>
              <given-names>MG</given-names>
            </name>
            <etal/>
            <collab>American College of Cardiology Foundation Task Force on Expert Consensus Documents</collab>
          </person-group>
          <article-title>ACCF/ACR/AHA/NASCI/SCMR 2010 expert consensus document on cardiovascular magnetic resonance: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents</article-title>
          <source>Circulation</source>
          <year>2010</year>
          <volume>121</volume>
          <issue>22</issue>
          <fpage>2462</fpage>
          <lpage>2508</lpage>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation. 1999;100(19):1992-2002.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kim</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Fieno</surname>
              <given-names>DS</given-names>
            </name>
            <name>
              <surname>Parrish</surname>
              <given-names>TB</given-names>
            </name>
            <name>
              <surname>Harris</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Simonetti</surname>
              <given-names>O</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function</article-title>
          <source>Circulation</source>
          <year>1999</year>
          <volume>100</volume>
          <issue>19</issue>
          <fpage>1992</fpage>
          <lpage>2002</lpage>
        </element-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <mixed-citation>Simonetti OP, Kim RJ, Fieno DS, Hillenbrand HB, Wu E, Bundy JM, et al. An improved MR imaging technique for the visualization of myocardial infarction. Radiology. 2001;218(1):215-23.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Simonetti</surname>
              <given-names>OP</given-names>
            </name>
            <name>
              <surname>Kim</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Fieno</surname>
              <given-names>DS</given-names>
            </name>
            <name>
              <surname>Hillenbrand</surname>
              <given-names>HB</given-names>
            </name>
            <name>
              <surname>Wu</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Bundy</surname>
              <given-names>JM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>An improved MR imaging technique for the visualization of myocardial infarction</article-title>
          <source>Radiology</source>
          <year>2001</year>
          <volume>218</volume>
          <issue>1</issue>
          <fpage>215</fpage>
          <lpage>223</lpage>
        </element-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <mixed-citation>Lima JA, Judd RM, Bazille A, Schulman SP, Atalar E, Zerhouni EA. Regional heterogeneity of human myocardial infarcts demonstrated by contrast-enhanced MRI. Potential mechanisms. Circulation. 1995;92(5):1117-25.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lima</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Judd</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Bazille</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Schulman</surname>
              <given-names>SP</given-names>
            </name>
            <name>
              <surname>Atalar</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Zerhouni</surname>
              <given-names>EA</given-names>
            </name>
          </person-group>
          <article-title>Regional heterogeneity of human myocardial infarcts demonstrated by contrast-enhanced MRI. Potential mechanisms</article-title>
          <source>Circulation</source>
          <year>1995</year>
          <volume>92</volume>
          <issue>5</issue>
          <fpage>1117</fpage>
          <lpage>1125</lpage>
        </element-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <mixed-citation>McConnell MV, Ganz P, Selwyn AP, Li W, Edelman RR, Manning WJ. Identification of anomalous coronary arteries and their anatomic course by magnetic resonance coronary angiography. Circulation. 1995;92(11):3158-62.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>McConnell</surname>
              <given-names>MV</given-names>
            </name>
            <name>
              <surname>Ganz</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Selwyn</surname>
              <given-names>AP</given-names>
            </name>
            <name>
              <surname>Li</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Edelman</surname>
              <given-names>RR</given-names>
            </name>
            <name>
              <surname>Manning</surname>
              <given-names>WJ</given-names>
            </name>
          </person-group>
          <article-title>Identification of anomalous coronary arteries and their anatomic course by magnetic resonance coronary angiography</article-title>
          <source>Circulation</source>
          <year>1995</year>
          <volume>92</volume>
          <issue>11</issue>
          <fpage>3158</fpage>
          <lpage>3162</lpage>
        </element-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <mixed-citation>Weiner DA, Ryan TJ, McCabe CH, Chaitman BR, Sheffield LT, Ferguson JC, et al. Prognostic importance of a clinical profile and exercise test in medically treated patients with coronary artery disease. J Am Coll Cardiol. 1984;3(3):772-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Weiner</surname>
              <given-names>DA</given-names>
            </name>
            <name>
              <surname>Ryan</surname>
              <given-names>TJ</given-names>
            </name>
            <name>
              <surname>McCabe</surname>
              <given-names>CH</given-names>
            </name>
            <name>
              <surname>Chaitman</surname>
              <given-names>BR</given-names>
            </name>
            <name>
              <surname>Sheffield</surname>
              <given-names>LT</given-names>
            </name>
            <name>
              <surname>Ferguson</surname>
              <given-names>JC</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Prognostic importance of a clinical profile and exercise test in medically treated patients with coronary artery disease</article-title>
          <source>J Am Coll Cardiol</source>
          <year>1984</year>
          <volume>3</volume>
          <issue>3</issue>
          <fpage>772</fpage>
          <lpage>779</lpage>
        </element-citation>
      </ref>
      <ref id="B21">
        <label>21</label>
        <mixed-citation>Effect of enalapril on mortality and the development of the heart failure in asymptomatic patients with reduced left ventricular ejection tractions. The SOLVD Investigators. N Engl J Med. 1992;327(10):685-91. Erratum in N Engl J Med. 1992;327(24):1768.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effect of enalapril on mortality and the development of the heart failure in asymptomatic patients with reduced left ventricular ejection tractions. The SOLVD Investigators</article-title>
          <source>N Engl J Med</source>
          <year>1992</year>
          <volume>327</volume>
          <issue>10</issue>
          <fpage>685</fpage>
          <lpage>691</lpage>
          <comment>Erratum in N Engl J Med. 1992;327(24):1768.</comment>
        </element-citation>
      </ref>
      <ref id="B22">
        <label>22</label>
        <mixed-citation>Pfeffer MA, Braunwald E, Moy&#233; LA, Basta L, Brown EJ Jr, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results on the Survival and Ventricular Enlargement (SAVE) Trial. N Engl J Med. 1992;327(10):669-77.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pfeffer</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Braunwald</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Moy&#233;</surname>
              <given-names>LA</given-names>
            </name>
            <name>
              <surname>Basta</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Brown</surname>
              <given-names>EJ</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Cuddy</surname>
              <given-names>TE</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results on the Survival and Ventricular Enlargement (SAVE) Trial</article-title>
          <source>N Engl J Med</source>
          <year>1992</year>
          <volume>327</volume>
          <issue>10</issue>
          <fpage>669</fpage>
          <lpage>677</lpage>
        </element-citation>
      </ref>
      <ref id="B23">
        <label>23</label>
        <mixed-citation>Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342(3):147-53. Erratum in N Engl J Med. 2000;342(10):748.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Yusuf</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Sleight</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Pogue</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Bosch</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Davies</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Dagenais</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
          <article-title>Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators</article-title>
          <source>N Engl J Med</source>
          <year>2000</year>
          <volume>342</volume>
          <issue>3</issue>
          <fpage>147</fpage>
          <lpage>153</lpage>
          <comment>Erratum in N Engl J Med. 2000;342(10):748.</comment>
        </element-citation>
      </ref>
      <ref id="B24">
        <label>24</label>
        <mixed-citation>Fox KM. EURopean trial On reduction of cardiac events with Perindopril instable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362(9386):782-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fox</surname>
              <given-names>KM</given-names>
            </name>
            <collab>EURopean trial On reduction of cardiac events with Perindopril instable coronary Artery disease Investigators</collab>
          </person-group>
          <article-title>Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study)</article-title>
          <source>Lancet</source>
          <year>2003</year>
          <volume>362</volume>
          <issue>9386</issue>
          <fpage>782</fpage>
          <lpage>788</lpage>
        </element-citation>
      </ref>
      <ref id="B25">
        <label>25</label>
        <mixed-citation>Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, et al; COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366(9497):1607-21.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chen</surname>
              <given-names>ZM</given-names>
            </name>
            <name>
              <surname>Jiang</surname>
              <given-names>LX</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>YP</given-names>
            </name>
            <name>
              <surname>Xie</surname>
              <given-names>JX</given-names>
            </name>
            <name>
              <surname>Pan</surname>
              <given-names>HC</given-names>
            </name>
            <name>
              <surname>Peto</surname>
              <given-names>R</given-names>
            </name>
            <etal/>
            <collab>COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group</collab>
          </person-group>
          <article-title>Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial</article-title>
          <source>Lancet</source>
          <year>2005</year>
          <volume>366</volume>
          <issue>9497</issue>
          <fpage>1607</fpage>
          <lpage>1621</lpage>
        </element-citation>
      </ref>
      <ref id="B26">
        <label>26</label>
        <mixed-citation>Stone PH, Gibson RS, Glasson SP, DeWood MA, Parker JD, Kawanishi DT, et al. Comparison of Propranolol, Diltiazem, and Nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Diferencial effects on ambulatory ischaemia exercise performance and angina symptoms. The ASIS Study Group. Circulation. 1990;82(6):1962-72.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Stone</surname>
              <given-names>PH</given-names>
            </name>
            <name>
              <surname>Gibson</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Glasson</surname>
              <given-names>SP</given-names>
            </name>
            <name>
              <surname>DeWood</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Parker</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Kawanishi</surname>
              <given-names>DT</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Comparison of Propranolol, Diltiazem, and Nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Diferencial effects on ambulatory ischaemia exercise performance and angina symptoms. The ASIS Study Group</article-title>
          <source>Circulation</source>
          <year>1990</year>
          <volume>82</volume>
          <issue>6</issue>
          <fpage>1962</fpage>
          <lpage>1972</lpage>
        </element-citation>
      </ref>
      <ref id="B27">
        <label>27</label>
        <mixed-citation>Marzilli M, Klein WW. Efficacy and tolerability of trimetazidine in stable angina: a meta-analysis of randomized, double-blind, controlled trials. Coron Artery Dis. 2003;14(2):171-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marzilli</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Klein</surname>
              <given-names>WW</given-names>
            </name>
          </person-group>
          <article-title>Efficacy and tolerability of trimetazidine in stable angina: a meta-analysis of randomized, double-blind, controlled trials</article-title>
          <source>Coron Artery Dis</source>
          <year>2003</year>
          <volume>14</volume>
          <issue>2</issue>
          <fpage>171</fpage>
          <lpage>179</lpage>
        </element-citation>
      </ref>
      <ref id="B28">
        <label>28</label>
        <mixed-citation>Tardif JC, Ponikowski P, Kahan T. Efficacy of the If current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy a 4-month, randomized, placebo-controlled trial. Eur Heart J. 2009;30(5):540-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tardif</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Ponikowski</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Kahan</surname>
              <given-names>T</given-names>
            </name>
          </person-group>
          <article-title>Efficacy of the If current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy a 4-month, randomized, placebo-controlled trial</article-title>
          <source>Eur Heart J</source>
          <year>2009</year>
          <volume>30</volume>
          <issue>5</issue>
          <fpage>540</fpage>
          <lpage>548</lpage>
        </element-citation>
      </ref>
      <ref id="B29">
        <label>29</label>
        <mixed-citation>Kloner RA, Hines ME, Geunes-Boyer S. Efficacy and safety of ranolazine in patients with chronic stable angina. Postgrad Med. 2013;125(6):43-52.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kloner</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Hines</surname>
              <given-names>ME</given-names>
            </name>
            <name>
              <surname>Geunes-Boyer</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
          <article-title>Efficacy and safety of ranolazine in patients with chronic stable angina</article-title>
          <source>Postgrad Med</source>
          <year>2013</year>
          <volume>125</volume>
          <issue>6</issue>
          <fpage>43</fpage>
          <lpage>52</lpage>
        </element-citation>
      </ref>
      <ref id="B30">
        <label>30</label>
        <mixed-citation>Sociedade Brasileira de Cardiologia. Diretrizes da cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica, valvopatias e doen&#231;as da aorta. Arq Bras Cardiol. 2004;82(supl. 5):1-21.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <collab>Sociedade Brasileira de Cardiologia</collab>
          </person-group>
          <article-title>Diretrizes da cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica, valvopatias e doen&#231;as da aorta</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2004</year>
          <volume>82</volume>
          <supplement>supl. 5</supplement>
          <fpage>1</fpage>
          <lpage>21</lpage>
        </element-citation>
      </ref>
      <ref id="B31">
        <label>31</label>
        <mixed-citation>Serryus PW, Morice MC, Kappetein P, Colombo A,Holmes DR, Mack MJ,et al;SYNTAX Investigators.Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. TRIAL.N Engl J Med. 2009;360(10):961-72. Erratum in N Engl J Med. 2013;368(6):584.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Serryus</surname>
              <given-names>PW</given-names>
            </name>
            <name>
              <surname>Morice</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Kappetein</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Colombo</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Holmes</surname>
              <given-names>DR</given-names>
            </name>
            <name>
              <surname>Mack</surname>
              <given-names>MJ</given-names>
            </name>
            <etal/>
            <collab>SYNTAX Investigators</collab>
          </person-group>
          <article-title>Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. TRIAL</article-title>
          <source>N Engl J Med</source>
          <year>2009</year>
          <volume>360</volume>
          <issue>10</issue>
          <fpage>961</fpage>
          <lpage>972</lpage>
          <comment>Erratum in N Engl J Med. 2013;368(6):584.</comment>
        </element-citation>
      </ref>
      <ref id="B32">
        <label>32</label>
        <mixed-citation>Hlatky MA, Boothroyd DB, Bravata DM, Boersma E, Booth J, Brooks MM, et al. Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials. Lancet. 2009;373(9670):1190-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hlatky</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Boothroyd</surname>
              <given-names>DB</given-names>
            </name>
            <name>
              <surname>Bravata</surname>
              <given-names>DM</given-names>
            </name>
            <name>
              <surname>Boersma</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Booth</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Brooks</surname>
              <given-names>MM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials</article-title>
          <source>Lancet</source>
          <year>2009</year>
          <volume>373</volume>
          <issue>9670</issue>
          <fpage>1190</fpage>
          <lpage>1197</lpage>
        </element-citation>
      </ref>
      <ref id="B33">
        <label>33</label>
        <mixed-citation>Hakeem A, Garg N, Bhatti S, Rajpurohit N, Ahmed Z, Uretsky BF. Effectiveness of percutaneous coronary intervention with drug-eluting stents compared with bypass surgery in diabetics with multivessel coronary disease: comprehensive systematic review and meta-analysis of randomized clinical data. J Am Heart Assoc. 2013;2(4):e000354.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hakeem</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Garg</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Bhatti</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Rajpurohit</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Ahmed</surname>
              <given-names>Z</given-names>
            </name>
            <name>
              <surname>Uretsky</surname>
              <given-names>BF</given-names>
            </name>
          </person-group>
          <article-title>Effectiveness of percutaneous coronary intervention with drug-eluting stents compared with bypass surgery in diabetics with multivessel coronary disease: comprehensive systematic review and meta-analysis of randomized clinical data</article-title>
          <source>J Am Heart Assoc</source>
          <year>2013</year>
          <volume>2</volume>
          <issue>4</issue>
          <elocation-id>e000354</elocation-id>
        </element-citation>
      </ref>
      <ref id="B34">
        <label>34</label>
        <mixed-citation>Stettler C, Allemann S, Wandel S, Kastrati A, Morice MC, Sch&#246;mig A, et al. Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis. BMJ. 2008;337:a1331.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Stettler</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Allemann</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Wandel</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Kastrati</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Morice</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Sch&#246;mig</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis</article-title>
          <source>BMJ</source>
          <year>2008</year>
          <volume>337</volume>
          <fpage>a1331</fpage>
          <lpage>a1331</lpage>
        </element-citation>
      </ref>
      <ref id="B35">
        <label>35</label>
        <mixed-citation>Grines CL, Bonow RO, Casey DE Jr, Gardner TJ, Lockhart PB, Moliterno DJ, et al; American Heart Association; American College of Cardiology; Society for Cardiovascular Angiography and Interventions; American College of Surgeons; American Dental Association; American College of Physicians. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. J Am Coll Cardiol. 2007;49(6):734-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Grines</surname>
              <given-names>CL</given-names>
            </name>
            <name>
              <surname>Bonow</surname>
              <given-names>RO</given-names>
            </name>
            <name>
              <surname>Casey</surname>
              <given-names>DE</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Gardner</surname>
              <given-names>TJ</given-names>
            </name>
            <name>
              <surname>Lockhart</surname>
              <given-names>PB</given-names>
            </name>
            <name>
              <surname>Moliterno</surname>
              <given-names>DJ</given-names>
            </name>
            <etal/>
            <collab>American Heart Association</collab>
            <collab>American College of Cardiology</collab>
            <collab>Society for Cardiovascular Angiography and Interventions</collab>
            <collab>American College of Surgeons</collab>
            <collab>American Dental Association</collab>
            <collab>American College of Physicians</collab>
          </person-group>
          <article-title>Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2007</year>
          <volume>49</volume>
          <issue>6</issue>
          <fpage>734</fpage>
          <lpage>739</lpage>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="SA1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Especial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Resumo Executivo da Diretriz de Doen&#231;a Coron&#225;ria Est&#225;vel</article-title>
      </title-group>
      <author-notes>
        <corresp id="c02"><bold>Correspond&#234;ncia: Luiz Antonio Machado C&#233;sar</bold>, Av. Dr. En&#233;as de Carvalho Aguiar, 44. Cerqueira Cesar, CEP 05403-000. S&#227;o Paulo, SP &#8211; Brasil Email: <email>luiz.cesar@incor.usp.br</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: C&#233;sar LAM, Mansur AP, Ferreira JFM.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesse</bold>
          </p>
          <p>Drs. Luiz Antonio Machado C&#233;sar e Jo&#227;o Fernando Monteiro Ferreira participaram de estudos cl&#237;nicos e/ou experimentais subvencionados pela Servier e Astra-Zeneca.</p>
          <p>Dr. Luiz Antonio Machado C&#233;sar foi palestrante em eventos ou atividades patrocinadas pela Servier e Astra-Zeneca; Foi (&#233;) membro do conselho consultivo ou diretivo da Servier e Astra- Zeneca; Participou de comit&#234;s normativos de estudos cient&#237;ficos patrocinados pela Servier e Astra-Zeneca; Recebeu aux&#237;lio pessoal ou institucional da Servier e Astra-Zeneca; Elaborou textos cient&#237;ficos em peri&#243;dicos patrocinados pela Servier e Astra-Zeneca.</p>
        </fn>
      </author-notes>
      <kwd-group>
        <title>Palavras-chave</title>
        <kwd>Doen&#231;a da Art&#233;ria Coronariana</kwd>
        <kwd>Diagn&#243;stico</kwd>
        <kwd>Exame F&#237;sico</kwd>
        <kwd>Fatores de Risco</kwd>
        <kwd>Aterosclerose</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec>
        <title>Parte I &#8211; Diagn&#243;stico e estratifica&#231;&#227;o de risco</title>
        <sec>
          <title>Introdu&#231;&#227;o</title>
          <p>Esta diretriz visa orientar todos os m&#233;dicos, especialmente os cardiologistas, para reconhecerem, o mais precocemente poss&#237;vel, adultos com risco elevado de doen&#231;a coronariana, bem como destacar os sintomas mais comuns para sua identifica&#231;&#227;o, principalmente os da doen&#231;a arterial coron&#225;ria (DAC).</p>
          <p>No Brasil, dados do Departamento de Inform&#225;tica do Sistema &#218;nico de Sa&#250;de (DATASUS) mostram que a causa cardiovascular corresponde a cerca de 30% das causas de morte<xref ref-type="bibr" rid="B01">1</xref>.</p>
          <list list-type="bullet">
            <title>Graus de recomenda&#231;&#227;o:</title>
            <list-item>
              <p>Classe I: condi&#231;&#245;es para as quais h&#225; evid&#234;ncias conclusivas e, na sua falta, consenso geral de que o procedimento &#233; seguro e &#250;til/eficaz;</p>
            </list-item>
            <list-item>
              <p>Classe II: condi&#231;&#245;es para as quais h&#225; evid&#234;ncias conflitantes e/ou diverg&#234;ncia de opini&#227;o sobre seguran&#231;a e utilidade/efic&#225;cia do procedimento;</p>
            </list-item>
            <list-item>
              <p>Classe IIa: peso ou evid&#234;ncia/opini&#227;o a favor do procedimento. Aprovado pela maioria dos profissionais;</p>
            </list-item>
            <list-item>
              <p>Classe IIb: seguran&#231;a e utilidade/efic&#225;cia menos bem estabelecidas, n&#227;o havendo predom&#237;nio de opini&#245;es a favor do procedimento;</p>
            </list-item>
            <list-item>
              <p>Classe III: condi&#231;&#245;es para as quais h&#225; evid&#234;ncias e/ou consenso de que o procedimento n&#227;o &#233; &#250;til/eficaz e, em alguns casos, pode ser prejudicial.</p>
            </list-item>
          </list>
          <list list-type="bullet">
            <title>N&#237;vel de evid&#234;ncia:</title>
            <list-item>
              <p>N&#237;vel A: dados obtidos a partir de m&#250;ltiplos estudos randomizados de bom porte concordantes e/ou de meta-an&#225;lise sistematizada robusta de estudos cl&#237;nicos randomizados;</p>
            </list-item>
            <list-item>
              <p>N&#237;vel B: dados obtidos a partir de meta-an&#225;lise menos robusta, de um &#250;nico estudo randomizado ou de estudos n&#227;o randomizados (observacionais);</p>
            </list-item>
            <list-item>
              <p>N&#237;vel C: dados obtidos de opini&#245;es consensuais de especialistas.</p>
            </list-item>
          </list>
        </sec>
        <sec>
          <title>Diagn&#243;stico</title>
          <sec>
            <title>Diagn&#243;stico de DAC subcl&#237;nica</title>
            <p>A estimativa do risco de doen&#231;a arterial pode ser avaliada pelo somat&#243;rio do risco individual considerando o sinergismo entre os reconhecidos fatores de risco para doen&#231;a cardiovascular. Diante da complexidade dessas intera&#231;&#245;es, uma atribui&#231;&#227;o intuitiva do risco frequentemente resulta em subestima&#231;&#227;o ou superestima&#231;&#227;o dos casos de maior ou menor risco, respectivamente.</p>
            <sec>
              <title>Diagn&#243;stico em pacientes com sintomas</title>
              <p>Considera-se a proposta de Diamond e Forrester<xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B03">3</xref>(<xref ref-type="table" rid="t05">Tabela 1</xref>): Grau de recomenda&#231;&#227;o I, N&#237;vel de evid&#234;ncia B.</p>
              <table-wrap id="t05">
                <label>Tabela 1</label>
                <caption>
                  <title>Probabilidade pr&#233;-teste de doen&#231;a arterial coron&#225;ria em pacientes sintom&#225;ticos, de acordo com idade e sexo (Diamond/Forrester e CASS Data)</title>
                </caption>
                <table frame="hsides" rules="groups">
                  <thead>
                    <tr style="border-bottom-width:thin;border-bottom-style:solid">
                      <th rowspan="2" align="left" colspan="1">Idade (anos)</th>
                      <th colspan="2" align="center" rowspan="1">Dor tor&#225;cica n&#227;o anginosa</th>
                      <th colspan="2" align="center" rowspan="1">Angina at&#237;pica</th>
                      <th colspan="2" align="center" rowspan="1">Angina t&#237;pica</th>
                    </tr>
                    <tr>
                      <th align="center" rowspan="1" colspan="1">Homem</th>
                      <th align="center" rowspan="1" colspan="1">Mulher</th>
                      <th align="center" rowspan="1" colspan="1">Homem</th>
                      <th align="center" rowspan="1" colspan="1">Mulher</th>
                      <th align="center" rowspan="1" colspan="1">Homem</th>
                      <th align="center" rowspan="1" colspan="1">Mulher</th>
                    </tr>
                  </thead>
                  <tbody>
                    <tr>
                      <td align="left" rowspan="1" colspan="1">35</td>
                      <td align="center" rowspan="1" colspan="1">3-35</td>
                      <td align="center" rowspan="1" colspan="1">1-19</td>
                      <td align="center" rowspan="1" colspan="1">8-59</td>
                      <td align="center" rowspan="1" colspan="1">2-39</td>
                      <td align="center" rowspan="1" colspan="1">30-88</td>
                      <td align="center" rowspan="1" colspan="1">10-78</td>
                    </tr>
                    <tr>
                      <td align="left" rowspan="1" colspan="1">45</td>
                      <td align="center" rowspan="1" colspan="1">9-47</td>
                      <td align="center" rowspan="1" colspan="1">2-22</td>
                      <td align="center" rowspan="1" colspan="1">21-70</td>
                      <td align="center" rowspan="1" colspan="1">5-43</td>
                      <td align="center" rowspan="1" colspan="1">51-92</td>
                      <td align="center" rowspan="1" colspan="1">20-79</td>
                    </tr>
                    <tr>
                      <td align="left" rowspan="1" colspan="1">55</td>
                      <td align="center" rowspan="1" colspan="1">23-59</td>
                      <td align="center" rowspan="1" colspan="1">4-25</td>
                      <td align="center" rowspan="1" colspan="1">25-79</td>
                      <td align="center" rowspan="1" colspan="1">10-47</td>
                      <td align="center" rowspan="1" colspan="1">80-95</td>
                      <td align="center" rowspan="1" colspan="1">38-82</td>
                    </tr>
                    <tr>
                      <td align="left" rowspan="1" colspan="1">65</td>
                      <td align="center" rowspan="1" colspan="1">49-69</td>
                      <td align="center" rowspan="1" colspan="1">9-29</td>
                      <td align="center" rowspan="1" colspan="1">71-86</td>
                      <td align="center" rowspan="1" colspan="1">20-51</td>
                      <td align="center" rowspan="1" colspan="1">93-97</td>
                      <td align="center" rowspan="1" colspan="1">56-84</td>
                    </tr>
                  </tbody>
                </table>
              </table-wrap>
              <p>Para a avalia&#231;&#227;o do risco cardiovascular, foram utilizadas as diretrizes brasileiras de preven&#231;&#227;o de aterosclerose e a V Diretriz Brasileira de Dislipidemias e Preven&#231;&#227;o da Aterosclerose<xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B05">5</xref> (Grau de recomenda&#231;&#227;o IIa, N&#237;vel de evid&#234;ncia B).</p>
            </sec>
          </sec>
          <sec>
            <title>Diagn&#243;stico de doen&#231;a arterial coron&#225;ria manifesta</title>
            <sec>
              <title>Hist&#243;ria, exame f&#237;sico, diagn&#243;stico diferencial</title>
              <sec>
                <title>Defini&#231;&#227;o de angina</title>
                <p>A angina &#233; uma s&#237;ndrome cl&#237;nica caracterizada por dor ou desconforto em quaisquer das seguintes regi&#245;es: t&#243;rax, epig&#225;strio, mand&#237;bula, ombro, dorso ou membros superiores, desencadeada ou agravada por atividade f&#237;sica ou estresse emocional, e atenuada com uso de nitroglicerina e derivados.</p>
              </sec>
              <sec>
                <title>Avalia&#231;&#227;o cl&#237;nica dos pacientes com dor tor&#225;cica</title>
                <p><bold>a) Hist&#243;ria cl&#237;nica:</bold> Uma hist&#243;ria cl&#237;nica detalhada. Algumas caracter&#237;sticas dos sintomas devem ser cuidadosamente indagadas, com a finalidade de orientar a probabilidade da presen&#231;a de angina:</p>
                <p>qualidade: constri&#231;&#227;o, aperto, peso, opress&#227;o, desconforto, queima&#231;&#227;o e pontada; localiza&#231;&#227;o: precordial, retroesternal, ombro, epig&#225;strio, cervical, hemit&#243;rax e dorso; irradia&#231;&#227;o: membros superiores (direito, esquerdo ou ambos), ombro, mand&#237;bula, pesco&#231;o, dorso e regi&#227;o epig&#225;strica; dura&#231;&#227;o: segundos, minutos, horas e dias; fatores desencadeantes: esfor&#231;o f&#237;sico, atividade sexual, posi&#231;&#227;o, alimenta&#231;&#227;o, respira&#231;&#227;o, componente emocional, e espont&#226;nea; fatores de al&#237;vio: repouso, nitrato sublingual, analg&#233;sico, alimenta&#231;&#227;o, anti&#225;cido, posi&#231;&#227;o e apneia; sintomas associados: sudorese, n&#225;usea, v&#244;mito, palidez, dispneia, hemoptise, tosse, pr&#233;&#8209;s&#237;ncope e s&#237;ncope.</p>
                <p>Um epis&#243;dio de angina dura alguns minutos, e normalmente &#233; precipitada por exerc&#237;cio f&#237;sico ou estresse emocional, com frequente melhora ou al&#237;vio ao repouso. O uso de compostos de nitroglicerina, como o nitrato sublingual, alivia a angina em aproximadamente 1 minuto. Dor localizada nas regi&#245;es das articula&#231;&#245;es condroesternais dificilmente tem origem card&#237;aca.</p>
                <p>A classifica&#231;&#227;o de angina mais utilizada &#233; a da Canadan Cardiovascular Society(CCS)<xref ref-type="bibr" rid="B06">6</xref> (<xref ref-type="table" rid="t06">Quadro 1</xref>).</p>
                <table-wrap id="t06">
                  <label>Quadro 1</label>
                  <caption>
                    <title>Gradua&#231;&#227;o da angina de peito, segundo a Sociedade Canadense Cardiovascular</title>
                  </caption>
                  <table frame="hsides" rules="groups">
                    <tbody>
                      <tr>
                        <td align="left" rowspan="1" colspan="1">Classe I</td>
                        <td align="left" rowspan="1" colspan="1">Atividade f&#237;sica habitual, como caminhar e subir escadas, n&#227;o provoca angina. Angina ocorre durante esfor&#231;os f&#237;sicos prolongados e intensos.</td>
                      </tr>
                      <tr>
                        <td align="left" rowspan="1" colspan="1">Classe II</td>
                        <td align="left" rowspan="1" colspan="1">Discreta limita&#231;&#227;o para atividades habituais. A angina ocorre ao caminhar ou subir escadas rapidamente, caminhar em aclives, caminhar ou subir escadas ap&#243;s refei&#231;&#245;es, no frio, ao vento, ou sob estresse emocional, ou em poucas horas ap&#243;s despertar. A angina ocorre ap&#243;s caminhar dois quarteir&#245;es planos ou subir mais de um lance de escada em condi&#231;&#245;es normais.</td>
                      </tr>
                      <tr>
                        <td align="left" rowspan="1" colspan="1">Classe III</td>
                        <td align="left" rowspan="1" colspan="1">Limita&#231;&#227;o com atividades habituais. A angina ocorre ap&#243;s caminhar um quarteir&#227;o plano ou subir um lance de escada.</td>
                      </tr>
                      <tr>
                        <td align="left" rowspan="1" colspan="1">Classe IV</td>
                        <td align="left" rowspan="1" colspan="1">Incapacidade de realizar qualquer atividade habitual sem desconforto &#8722; os sintomas anginosos podem estar presentes no repouso.</td>
                      </tr>
                    </tbody>
                  </table>
                </table-wrap>
                <p><bold>b) Exame f&#237;sico:</bold> O exame f&#237;sico &#233; usualmente normal nos pacientes com angina est&#225;vel. Entretanto, durante o epis&#243;dio anginoso, pode fornecer ind&#237;cios valiosos a respeito da exist&#234;ncia ou n&#227;o de DAC. Quando &#233; poss&#237;vel realizar exame f&#237;sico do paciente na vig&#234;ncia de dor, Terceira Bulha (B3), Quarta Bulha (B4) ou galope, sopro de regurgita&#231;&#227;o mitral, desdobramento paradoxal de Segunda Bulha (B2) e estertores crepitantes bibasais s&#227;o achados sugestivos e preditores de DAC<xref ref-type="bibr" rid="B07">7</xref>. A ocorr&#234;ncia de aterosclerose em outras &#225;reas, como pulsos de membros inferiores diminu&#237;dos, endurecimento arterial e aneurisma abdominal aumentam a probabilidade de DAC.</p>
              </sec>
              <sec>
                <title>Diagn&#243;stico diferencial da dor tor&#225;cica: condi&#231;&#245;es associadas, fatores provocadores e de al&#237;vio da angina</title>
                <p>Em todos os pacientes, especialmente naqueles com angina t&#237;pica, devem ser consideradas as doen&#231;as associadas (simult&#226;neas) que possam precipitar angina "funcional", isto &#233;, isquemia mioc&#225;rdica na aus&#234;ncia de obstru&#231;&#227;o coronariana anat&#244;mica significante. Geralmente, s&#227;o doen&#231;as que causam isquemia mioc&#225;rdica, por aumentarem o consumo de oxig&#234;nio pelo mioc&#225;rdio ou por diminu&#237;rem sua oferta. Um aumento no consumo de oxig&#234;nio pode ser causado por hipertermia, hipertireoidismo e uso de coca&#237;na. A apneia do sono obstrutiva deve ser seriamente considerada em pacientes que apresentam sintomas noturnos expressivos.</p>
              </sec>
            </sec>
            <sec>
              <title>Testes n&#227;o invasivos</title>
              <p>Os testes adicionais na angina est&#225;vel s&#227;o baseados na probabilidade de DAC. Ap&#243;s a probabilidade ter sido estimada, ela &#233; categorizada como baixa, intermedi&#225;ria e alta, de acordo com valores estabelecidos: 10 a 90% nos casos intermedi&#225;rios, &lt; 10% nos casos de baixa probabilidade e &gt; 90% nos casos de alta probabilidade.</p>
              <p>Como a mortalidade geral de pacientes com angina est&#225;vel est&#225; entre 1,2 a 2,4% ao ano<xref ref-type="bibr" rid="B08">8</xref>, um m&#233;todo diagn&#243;stico que conduzisse a uma incid&#234;ncia maior de complica&#231;&#245;es e morte seria inadequado.</p>
              <sec>
                <title>Eletrocardiograma</title>
                <p>Indicado na suspeita de causa card&#237;aca para dor tor&#225;cica (Grau de recomenda&#231;&#227;o I, N&#237;vel de evid&#234;ncia B).</p>
              </sec>
              <sec>
                <title>Radiografia de t&#243;rax</title>
                <p>O Rx &#233; indicado a pacientes com DAC e sinais ou sintomas de insufici&#234;ncia card&#237;aca congestiva (Grau de recomenda&#231;&#227;o I, N&#237;vel de evid&#234;ncia B); e pacientes com sinais e sintomas de doen&#231;a pulmonar (Grau de recomenda&#231;&#227;o IIa, N&#237;vel de evid&#234;ncia B).</p>
              </sec>
              <sec>
                <title>Teste ergom&#233;trico</title>
                <p>As vari&#225;veis mais preditivas relacionadas ao diagn&#243;stico de obstru&#231;&#227;o coronariana s&#227;o depress&#227;o do segmento ST &#8805; 1 mm (medido a 0,80 segundos do ponto J), com configura&#231;&#227;o horizontal ou descendente, e a presen&#231;a da dor anginosa.</p>
                <sec>
                  <title>
                    <underline>Utiliza&#231;&#227;o do teste ergom&#233;trico para diagn&#243;stico de obstru&#231;&#227;o coronariana</underline>
                  </title>
                  <p>
                    <bold>Grau de recomenda&#231;&#227;o I, N&#237;vel de evid&#234;ncia B</bold>
                  </p>
                  <list list-type="simple">
                    <list-item>
                      <p>1. Probabilidade intermedi&#225;ria</p>
                    </list-item>
                  </list>
                  <p>
                    <bold>Grau de recomenda&#231;&#227;o IIa, N&#237;vel de evid&#234;ncia B</bold>
                  </p>
                  <list list-type="order">
                    <list-item>
                      <p>Suspeita de angina vasoesp&#225;tica.</p>
                    </list-item>
                    <list-item>
                      <p>Ap&#243;s angiografia coron&#225;ria para avalia&#231;&#227;o de les&#245;es intermedi&#225;rias.</p>
                    </list-item>
                    <list-item>
                      <p>Indiv&#237;duos assintom&#225;ticos com mais de dois fatores de risco.</p>
                    </list-item>
                  </list>
                  <p>
                    <bold>Grau de recomenda&#231;&#227;o IIb, N&#237;vel de evid&#234;ncia B</bold>
                  </p>
                  <list list-type="order">
                    <list-item>
                      <p>Alta ou baixa probabilidade pr&#233;-teste de obstru&#231;&#227;o da coron&#225;ria, com base em idade, sexo e sintomas.</p>
                    </list-item>
                    <list-item>
                      <p>Avalia&#231;&#227;o de risco para cirurgia n&#227;o card&#237;aca (em baixo risco cardiovascular).</p>
                    </list-item>
                  </list>
                  <p><bold>Grau de recomenda&#231;&#227;o III:</bold> anormalidades: s&#237;ndrome de pr&#233;-excita&#231;&#227;o ou de Wolff-Parkinson-White (WPW), ritmo de marca-passo, depress&#227;o do segmento ST &gt; 1 mm no repouso e bloqueio completo do ramo esquerdo.</p>
                  <p>
                    <italic>Ecocardiografia</italic>
                  </p>
                  <p>Pode auxiliar no diagn&#243;stico<xref ref-type="bibr" rid="B09">9</xref>, ao demonstrar anormalidades, revers&#237;veis ou n&#227;o, da motilidade segmentar em pacientes com quadro cl&#237;nico de DAC.</p>
                  <sec>
                    <title>Ecocardiografia</title>
                    <p><bold>a) Uso da ecocardiografia sob estresse na DAC cr&#244;nica:</bold>o exame &#233; utilizado na avalia&#231;&#227;o de diagn&#243;stico e progn&#243;stico, na avalia&#231;&#227;o do impacto de terapias de revasculariza&#231;&#227;o, na detec&#231;&#227;o de viabilidade mioc&#225;rdica e no aux&#237;lio &#224;s decis&#245;es terap&#234;uticas. Apresenta boa acur&#225;cia para detec&#231;&#227;o de isquemia mioc&#225;rdica induzida em pacientes com probabilidade pr&#233;-teste intermedi&#225;ria ou alta e, comparada ao teste ergom&#233;trico, tem maior sensibilidade e especificidade para o diagn&#243;stico<xref ref-type="bibr" rid="B10">10</xref>.</p>
                    <p><bold>b) Avalia&#231;&#227;o pr&#233;-operat&#243;ria:</bold> de acordo com as recomenda&#231;&#245;es da ACC/AHA e da<italic> European Association of Echocardiography</italic>, a ecocardiografia sob estresse com dobutamina tem sido de grande valia para a estratifica&#231;&#227;o de risco pr&#233;-operat&#243;rio de pacientes com DAC<xref ref-type="bibr" rid="B11">11</xref>.</p>
                  </sec>
                  <sec>
                    <title>Radiois&#243;topos</title>
                    <p>Avaliam-se aspectos de perfus&#227;o mioc&#225;rdica, integridade celular, metabolismo mioc&#225;rdico, contratilidade mioc&#225;rdica e fun&#231;&#227;o ventricular global ou segmentar<xref ref-type="bibr" rid="B12">12</xref>. Por estar associado &#224; maior radia&#231;&#227;o, o radiois&#243;topo T&#225;lio-201 &#233; menos utilizado, sendo indicado na pesquisa de isquemia concomitante a mioc&#225;rdio vi&#225;vel.</p>
                  </sec>
                  <sec>
                    <title>Angiografia coronariana</title>
                    <p>As les&#245;es coronarianas s&#227;o significativas quando h&#225; obstru&#231;&#227;o de uma ou mais art&#233;rias epic&#225;rdicas, com no m&#237;nimo 70% de estenose, e/ou les&#227;o obstrutiva no tronco de art&#233;ria coron&#225;ria esquerda, com no m&#237;nimo 50% de estenose, sendo tais obstru&#231;&#245;es avaliadas e mensuradas pela CATE (<xref ref-type="table" rid="t07">Quadro 2</xref>).</p>
                    <table-wrap id="t07">
                      <label>Quadro 2</label>
                      <caption>
                        <title>Recomenda&#231;&#245;es para angiografia coronariana em pacientes com doen&#231;a arterial coron&#225;ria</title>
                      </caption>
                      <table frame="hsides" rules="groups">
                        <tbody>
                          <tr align="left">
                            <td rowspan="4" colspan="1">Classe I</td>
                            <td rowspan="1" colspan="1">Angina est&#225;vel (CCS III ou IV) independetemente do tratamento cl&#237;nico (B)</td>
                          </tr>
                          <tr>
                            <td align="left" rowspan="1" colspan="1">Alto risco em testes n&#227;o invasivos, independentemente da angina (B)</td>
                          </tr>
                          <tr>
                            <td align="left" rowspan="1" colspan="1">Angina e sobreviventes de parada card&#237;aca ou de arritmia ventricular grave (B)</td>
                          </tr>
                          <tr>
                            <td align="left" rowspan="1" colspan="1">Angina e sintomas/sinais de insufici&#234;ncia card&#237;aca congestiva (C)</td>
                          </tr>
                          <tr align="left">
                            <td rowspan="4" colspan="1">Classe IIa</td>
                            <td rowspan="1" colspan="1">Pacientes com diagn&#243;stico incerto ap&#243;s testes n&#227;o invasivos, quando os benef&#237;cios de um diagn&#243;stico preciso superam os riscos e custos da angiografia coron&#225;ria (C)</td>
                          </tr>
                          <tr>
                            <td align="left" rowspan="1" colspan="1">Impossibilidade de se submeter a testes n&#227;o invasivos por incapacidade f&#237;sica, doen&#231;a ou obesidade (C)</td>
                          </tr>
                          <tr>
                            <td align="left" rowspan="1" colspan="1">Profiss&#245;es de risco que requerem um diagn&#243;stico preciso (C)</td>
                          </tr>
                          <tr>
                            <td align="left" rowspan="1" colspan="1">Pacientes com informa&#231;&#245;es progn&#243;sticas incertas ap&#243;s testes n&#227;o invasivos (C)</td>
                          </tr>
                          <tr align="left">
                            <td rowspan="1" colspan="1">Classe IIb</td>
                            <td rowspan="1" colspan="1">M&#250;ltiplas interna&#231;&#245;es por dor tor&#225;cica, quando um diagn&#243;stico definitivo &#233; considerado necess&#225;rio (C)</td>
                          </tr>
                          <tr align="left">
                            <td rowspan="3" colspan="1">Classe III</td>
                            <td rowspan="1" colspan="1">Comorbidades significativas, quando os riscos da angiografia superam os benef&#237;cios do procedimento (C)</td>
                          </tr>
                          <tr>
                            <td align="left" rowspan="1" colspan="1">Angina est&#225;vel (CCS I ou II) que responde a tratamento medicamentoso e sem evid&#234;ncia de isquemia em testes n&#227;o invasivos (C)</td>
                          </tr>
                          <tr>
                            <td align="left" rowspan="1" colspan="1">Prefer&#234;ncia por evitar a revasculariza&#231;&#227;o (C)</td>
                          </tr>
                        </tbody>
                      </table>
                      <table-wrap-foot>
                        <fn id="TFN03">
                          <p>CCS: Canadian Cardiovascular Society.</p>
                        </fn>
                      </table-wrap-foot>
                    </table-wrap>
                  </sec>
                  <sec>
                    <title>Tomografia do Cora&#231;&#227;o</title>
                    <p>A Tomografia Computadorizada (TC) card&#237;aca oferece duas principais modalidades de exame, as quais empregam t&#233;cnicas diferentes e fornecem informa&#231;&#245;es distintas: o escore de c&#225;lcio e a angiotomografia coronariana.</p>
                    <p>
                      <bold>a) Escore de c&#225;lcio</bold>
                    </p>
                    <p>A quantifica&#231;&#227;o da calcifica&#231;&#227;o nas art&#233;rias coron&#225;rias pelo EC correlaciona-se com a carga de aterosclerose<xref ref-type="bibr" rid="B13">13</xref>.</p>
                    <p>
                      <bold>Grau de recomenda&#231;&#227;o I, N&#237;vel de evid&#234;ncia A</bold>
                    </p>
                    <p>Assintom&#225;ticos com risco risco intermedi&#225;rio ou pelo escore global.</p>
                    <p>
                      <bold>Grau de recomenda&#231;&#227;o IIa, N&#237;vel de evid&#234;ncia B</bold>
                    </p>
                    <p>Assintom&#225;ticos com baixo risco pelo escore de risco global e com antecedente familiar de DAC precoce.</p>
                    <p>
                      <bold>Grau de recomenda&#231;&#227;o III, N&#237;vel de evid&#234;ncia B</bold>
                    </p>
                    <list list-type="order">
                      <list-item>
                        <p>Pacientes assintom&#225;ticos de alto risco ou DAC j&#225; conhecida.</p>
                      </list-item>
                      <list-item>
                        <p>Seguimento da evolu&#231;&#227;o da calcifica&#231;&#227;o coron&#225;ria.</p>
                      </list-item>
                      <list-item>
                        <p>Pacientes sintom&#225;ticos.</p>
                      </list-item>
                    </list>
                    <p>A Angiotomografia Computadorizada das Art&#233;rias Coron&#225;rias (angio-TC) permite a avalia&#231;&#227;o da luz das art&#233;rias coron&#225;rias de maneira n&#227;o invasiva<xref ref-type="bibr" rid="B14">14</xref>.</p>
                    <p>As principais indica&#231;&#245;es cl&#237;nicas s&#227;o para pacientes sintom&#225;ticos com resultados discordantes entre m&#233;todos de isquemia e cl&#237;nica.</p>
                    <p>
                      <bold>Grau de recomenda&#231;&#227;o IIa, N&#237;vel de evid&#234;ncia A</bold>
                    </p>
                    <list list-type="simple">
                      <list-item>
                        <p>Suspeita de DAC cr&#244;nica com:</p>
                      </list-item>
                      <list-item>
                        <p>a) Testes de isquemia pr&#233;vios conflitantes ou inconclusivos;</p>
                      </list-item>
                      <list-item>
                        <p>b) Sintomas cont&#237;nuos e testes de isquemia normais ou inconclusivos;</p>
                      </list-item>
                    </list>
                    <p>
                      <bold>Grau de recomenda&#231;&#227;o IIa, N&#237;vel de evid&#234;ncia B</bold>
                    </p>
                    <list list-type="order">
                      <list-item>
                        <p>Avaliar a desobstru&#231;&#227;o de enxertos de revasculariza&#231;&#227;o mioc&#225;rdica em sintom&#225;ticos com probabilidade pr&#233;&#8209;teste moderado a alto.</p>
                      </list-item>
                    </list>
                    <p>
                      <bold>Grau de recomenda&#231;&#227;o IIb, N&#237;vel de evid&#234;ncia B</bold>
                    </p>
                    <list list-type="order">
                      <list-item>
                        <p>Sintom&#225;ticos com probabilidade intermedi&#225;ria de DAC e testes de isquemia positivos.</p>
                      </list-item>
                      <list-item>
                        <p>Sintom&#225;ticos com baixa probabilidade de DAC com testes de isquemia negativos.</p>
                      </list-item>
                      <list-item>
                        <p>Avalia&#231;&#227;o de reestenose intrastent em sintom&#225;ticos com probabilidade pr&#233;-teste intermedi&#225;ria.</p>
                      </list-item>
                    </list>
                    <p>
                      <bold>Grau de recomenda&#231;&#227;o III, N&#237;vel de evid&#234;ncia B</bold>
                    </p>
                    <list list-type="order">
                      <list-item>
                        <p>Sintom&#225;ticos com alta probabilidade de DAC.</p>
                      </list-item>
                      <list-item>
                        <p>Avalia&#231;&#227;o inicial de DAC em assintom&#225;ticos com capacidade de realizar exerc&#237;cio f&#237;sico e com eletrocardiograma interpret&#225;vel.</p>
                      </list-item>
                      <list-item>
                        <p>Seguimento de les&#245;es arterial coronarianas em indiv&#237;duos assintom&#225;ticos.</p>
                      </list-item>
                    </list>
                    <p>A resson&#226;ncia magn&#233;tica cardiovascular &#233; um excelente m&#233;todo diagn&#243;stico, pois permite, em um &#250;nico exame, a avalia&#231;&#227;o da anatomia card&#237;aca e vascular, da fun&#231;&#227;o ventricular, da perfus&#227;o mioc&#225;rdica e a caracteriza&#231;&#227;o tecidual de forma acurada e reprodut&#237;vel<xref ref-type="bibr" rid="B15">15</xref>.</p>
                    <p>
                      <bold> a) Isquemia mioc&#225;rdica</bold>
                    </p>
                    <p>Os protocolos para o estudo de isquemia com perfus&#227;o mioc&#225;rdica por resson&#226;ncia magn&#233;tica s&#227;o similares aos utilizados em cintilografia.</p>
                    <p>
                      <bold>b) Realce tardio</bold>
                    </p>
                    <p>O diagn&#243;stico e a caracteriza&#231;&#227;o das regi&#245;es de infarto/necrose/fibrose do mioc&#225;rdio pela resson&#226;ncia magn&#233;tica card&#237;aca baseia-se na t&#233;cnica do realce tardio<xref ref-type="bibr" rid="B16">16</xref><sup>-</sup><xref ref-type="bibr" rid="B18">18</xref>.</p>
                    <p>
                      <bold>c) Angiorreson&#226;ncia das art&#233;rias coron&#225;rias</bold>
                    </p>
                    <p>Seu uso cl&#237;nico atualmente se concentra na avalia&#231;&#227;o de anomalias cong&#234;nitas, e da origem e trajeto das art&#233;rias coron&#225;rias<xref ref-type="bibr" rid="B19">19</xref>.</p>
                  </sec>
                </sec>
                <sec>
                  <title>
                    <underline>Recomenda&#231;&#245;es da resson&#226;ncia magn&#233;tica</underline>
                  </title>
                  <p>
                    <bold>Grau de recomenda&#231;&#227;o I, N&#237;vel de evid&#234;ncia A</bold>
                  </p>
                  <p>Avalia&#231;&#227;o da fun&#231;&#227;o ventricular global, volumes e massa (esquerda e direita)</p>
                  <p>Detec&#231;&#227;o de isquemia:</p>
                  <list list-type="bullet">
                    <list-item>
                      <p>Avalia&#231;&#227;o da perfus&#227;o mioc&#225;rdica sob estresse com vasodilatadores.</p>
                    </list-item>
                    <list-item>
                      <p>Avalia&#231;&#227;o da contratilidade ventricular sob estresse com dobutamina.</p>
                    </list-item>
                    <list-item>
                      <p>Detec&#231;&#227;o e quantifica&#231;&#227;o de fibrose mioc&#225;rdica e massa infartada.</p>
                    </list-item>
                    <list-item>
                      <p>Avalia&#231;&#227;o da viabilidade mioc&#225;rdica.</p>
                    </list-item>
                  </list>
                  <p>
                    <bold>Grau de recomenda&#231;&#227;o I, N&#237;vel de evid&#234;ncia B</bold>
                  </p>
                  <p>Diferencia&#231;&#227;o entre cardiopatias isqu&#234;micas e n&#227;o isqu&#234;micas</p>
                  <list list-type="bullet">
                    <list-item>
                      <p>Angiorreson&#226;ncia das art&#233;rias coron&#225;rias:</p>
                    </list-item>
                    <list-item>
                      <p>Avalia&#231;&#227;o de anomalias cong&#234;nitas.</p>
                    </list-item>
                  </list>
                </sec>
              </sec>
            </sec>
          </sec>
          <sec>
            <title>Estratifica&#231;&#227;o do risco cardiovascular na DAC</title>
            <p>As estrat&#233;gias e m&#233;todos utilizados no diagn&#243;stico da DAC tamb&#233;m fornecem informa&#231;&#245;es sobre a gravidade da doen&#231;a, que influenciam na realiza&#231;&#227;o de m&#233;todos complementares invasivos, como coronariografia, e na decis&#227;o terap&#234;utica.</p>
            <sec>
              <title>Teste ergom&#233;trico para avalia&#231;&#227;o do progn&#243;stico da DAC</title>
              <p>
                <bold>Grau de recomenda&#231;&#227;o I, N&#237;vel de evid&#234;ncia B</bold>
              </p>
              <p>Pacientes com probabilidade intermedi&#225;ria ou alta de DAC ap&#243;s avalia&#231;&#227;o inicial; pacientes que apresentem modifica&#231;&#245;es de sintomas.</p>
              <p>
                <bold>Grau de recomenda&#231;&#227;o IIb, N&#237;vel de evid&#234;ncia B</bold>
              </p>
              <p>Portadores de pr&#233;-excita&#231;&#227;o, depress&#227;o do segmento ST &gt; 1 mm no ECG de repouso, ritmo de marca-passo e bloqueio completo de ramo esquerdo.</p>
              <p>
                <bold>Grau de recomenda&#231;&#227;o IIa, N&#237;vel de evid&#234;ncia C</bold>
              </p>
              <p>Pacientes revascularizados com sintomas sugestivos de isquemia.</p>
              <p>
                <bold>Grau de recomenda&#231;&#227;o III, N&#237;vel de evid&#234;ncia C</bold>
              </p>
              <p>Pacientes portadores de comorbidades graves.</p>
              <p>Nos pacientes capazes de atingir o est&#225;gio 3 do protocolo de Bruce, a taxa de mortalidade anual &#233; ao redor de 1%, ao passo que naqueles incapazes de ultrapassar os 5 METs, a mortalidade anual gira em torno de 5%<xref ref-type="bibr" rid="B20">20</xref>.</p>
              <p>Outras vari&#225;veis de alto risco s&#227;o: depress&#227;o do segmento ST em m&#250;ltiplas deriva&#231;&#245;es; depress&#227;o persistente do segmento ST na recupera&#231;&#227;o &gt; 5 minutos; inadequada resposta cronotr&#243;pica; queda da press&#227;o arterial sist&#243;lica durante o esfor&#231;o ou curva achatada; e arritmia ventricular grave em n&#237;vel baixo de esfor&#231;o, na presen&#231;a de depress&#227;o do segmento ST ou de dor anginosa.</p>
              <sec>
                <title>
                  <underline>Ecocardiograma com estresse para avaliar progn&#243;stico na DAC</underline>
                </title>
                <p>O ecocardiograma para avalia&#231;&#227;o do progn&#243;stico da DAC leva em conta principalmente a fun&#231;&#227;o ventricular esquerda, e a presen&#231;a ou aus&#234;ncia de isquemia mioc&#225;rdica induzida sob estresse f&#237;sico ou farmacol&#243;gico, avaliados pela ecocardiografia. Em pacientes assintom&#225;ticos submetidos &#224; CRM com sucesso, a avalia&#231;&#227;o rotineira pela ecocardiografia sob estresse n&#227;o &#233; necess&#225;ria nem indicada.</p>
              </sec>
            </sec>
          </sec>
          <sec>
            <title>Estrat&#233;gias para o diagn&#243;stico e estratifica&#231;&#227;o da DAC</title>
            <p>O progn&#243;stico de DAC tamb&#233;m por se basear na visualiza&#231;&#227;o direta e anat&#244;mica da les&#227;o coronariana pela angiografia coron&#225;ria. Um estudo funcional normal, realizado com protocolo adequado de estresse, resulta em mesmo progn&#243;stico que um exame de angiografia coron&#225;ria.</p>
          </sec>
        </sec>
      </sec>
      <sec>
        <title>Parte II &#8211; Tratamento Medicamentoso</title>
        <p>Os objetivos fundamentais do tratamento da DAC incluem prevenir o infarto do mioc&#225;rdio e reduzir a mortalidade, e reduzir os sintomas e a ocorr&#234;ncia da isquemia mioc&#225;rdica propiciando melhor qualidade de vida.</p>
        <sec>
          <title>Tratamentos medicamentosos para reduzir o risco de infarto do mioc&#225;rdio e mortalidade</title>
          <p><bold>a) &#193;cido Acetilsalic&#237;lico (AAS):</bold> Grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia A.</p>
          <p>
            <bold>b) Derivados tienopirid&#237;nicos:</bold>
          </p>
          <p>Clopidogrel: Grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia B. Quando o uso de aspirina &#233; absolutamente contraindicado; e associado &#224; aspirina ap&#243;s implante de   <italic>stent</italic>, por pelo menos 30 dias.</p>
          <p><bold>Ticlopidina:</bold> Grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia B. Quando o uso de aspirina &#233; absolutamente contraindicado; e associado &#224; aspirina ap&#243;s implante de stent, por pelo menos 30 dias.</p>
          <p><bold>c) Dipiridamol:</bold> Grau de recomenda&#231;&#227;o III, n&#237;vel de evid&#234;ncia B.</p>
          <p><bold>d) Anticoagulantes:</bold> devem ser utilizados associados &#224; aspirina na presen&#231;a de alto risco tromb&#243;tico, especialmente ap&#243;s infarto do mioc&#225;rdio. Grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia A.</p>
          <p>Como alternativa &#224; intoler&#226;ncia &#224; aspirina: Grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia A.</p>
          <p>Para situa&#231;&#245;es espec&#237;ficas e ap&#243;s implante de <italic>stents</italic> revestidos com antiproliferativos, consultar as Diretrizes Brasileiras de Antiagregantes Plaquet&#225;rios e Anticoagulantes em Cardiologia.</p>
          <p>Mudan&#231;a do Estilo de Vida (MEV) &#233; indicada a todos os pacientes com DAC (<xref ref-type="table" rid="t08">Quadro 3</xref>).</p>
          <table-wrap id="t08">
            <label>Quadro 3</label>
            <caption>
              <title>Recomenda&#231;&#245;es para o tratamento farmacol&#243;gico das dislipidemias</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th align="left" rowspan="1" colspan="1">Indica&#231;&#227;o</th>
                  <th align="center" rowspan="1" colspan="1">Classe</th>
                  <th align="center" rowspan="1" colspan="1">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left" rowspan="1" colspan="1">Estatinas como primeira op&#231;&#227;o medicamentosa na preven&#231;&#227;o prim&#225;ria e secund&#225;ria</td>
                  <td align="center" rowspan="1" colspan="1">I</td>
                  <td align="center" rowspan="1" colspan="1">A</td>
                </tr>
                <tr>
                  <td align="left" rowspan="1" colspan="1">Uso de fibratos em monoterapia ou em associa&#231;&#227;o &#224; estatina para prevenir doen&#231;as microvasculares em diab&#233;ticos tipo 2</td>
                  <td align="center" rowspan="1" colspan="1">I</td>
                  <td align="center" rowspan="1" colspan="1">A</td>
                </tr>
                <tr>
                  <td align="left" rowspan="1" colspan="1">Associa&#231;&#227;o de ezetimiba ou resinas &#224;s estatinas quando a meta dos n&#237;veis LDL-c n&#227;o &#233; alcan&#231;ada</td>
                  <td align="center" rowspan="1" colspan="1">IIa</td>
                  <td align="center" rowspan="1" colspan="1">C</td>
                </tr>
                <tr>
                  <td align="left" rowspan="1" colspan="1">Associa&#231;&#227;o de niacina &#224;s estatinas</td>
                  <td align="center" rowspan="1" colspan="1">III</td>
                  <td align="center" rowspan="1" colspan="1">A</td>
                </tr>
                <tr>
                  <td align="left" rowspan="1" colspan="1">&#193;cidos graxos &#244;mega-3 para preven&#231;&#227;o cardiovascular</td>
                  <td align="center" rowspan="1" colspan="1">IIII</td>
                  <td align="center" rowspan="1" colspan="1">A</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN04">
                <p>Fonte: Diretriz Brasileira de Preven&#231;&#227;o Cardiovascular<xref ref-type="bibr" rid="B10">10</xref>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p><bold>a) IECAs:</bold> os benef&#237;cios dos IECAs no tratamento da DAC foram comprovados em ensaios cl&#237;nicos que inclu&#237;ram pacientes assintom&#225;ticos com fra&#231;&#227;o de eje&#231;&#227;o reduzida<xref ref-type="bibr" rid="B21">21</xref> e indiv&#237;duos com disfun&#231;&#227;o ventricular ap&#243;s infarto agudo do mioc&#225;rdio<xref ref-type="bibr" rid="B21">21</xref><sup>,</sup><xref ref-type="bibr" rid="B22">22</xref>. Devem ser usados de rotina para o tratamento quando houver disfun&#231;&#227;o ventricular, e/ou insufici&#234;ncia card&#237;aca e/ou diabetes mellitus<xref ref-type="bibr" rid="B23">23</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref>. Grau de recomenda&#231;&#227;o, I N&#237;vel de evid&#234;ncia A.</p>
          <p>Devem ser usados de rotina em todos os pacientes com DAC: Grau de recomenda&#231;&#227;o IIa, N&#237;vel de evid&#234;ncia B.</p>
          <p><bold>b) Bloqueadores do receptor de angiotensina:</bold> terapia alternativa para os pacientes que n&#227;o toleram IECAs, j&#225; que nenhum estudo foi realizado com esse grupo de f&#225;rmacos na doen&#231;a coron&#225;ria est&#225;vel. Em outras situa&#231;&#245;es, n&#227;o oferecem benef&#237;cio adicional a dos aos IECAs, os quais reduzem a incid&#234;ncia de infarto.</p>
        </sec>
        <sec>
          <title>Tratamento para reduzir os sintomas e a isquemia mioc&#225;rdica</title>
          <p><bold>a) Bloqueadores beta-adren&#233;rgicos:</bold> droga de primeira escolha, isoladamente ou em associa&#231;&#227;o com outros agentes antianginosos. Agente de primeira linha em pacientes com angina est&#225;vel sem infarto do mioc&#225;rdio pr&#233;vio e/ou disfun&#231;&#227;o de VE<xref ref-type="bibr" rid="B25">25</xref>. Grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia B.</p>
          <list list-type="simple">
            <list-item>
              <p>&#8211; Agente de primeira linha em pacientes com angina est&#225;vel e at&#233; 2 anos ap&#243;s infarto do mioc&#225;rdio e/ou disfun&#231;&#227;o ventricular esquerda. Grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia A.</p>
            </list-item>
            <list-item>
              <p>&#8211; Para al&#237;vio sintom&#225;tico em pacientes com angina vasoesp&#225;stica. Grau de recomenda&#231;&#227;o III, n&#237;vel de evid&#234;ncia C.</p>
            </list-item>
          </list>
          <p><bold>b) Antagonistas de canais de c&#225;lcio:</bold> grupo heterog&#234;neo de medicamentos cujos efeitos farmacol&#243;gicos incluem relaxamento da musculatura lisa, redu&#231;&#227;o da p&#243;s-carga, e efeitos inotr&#243;picos negativos (algumas formula&#231;&#245;es). Por outro lado, est&#227;o contraindicados na presen&#231;a de disfun&#231;&#227;o ventricular (verapamil e diltiazem)<xref ref-type="bibr" rid="B26">26</xref>.</p>
          <list list-type="simple">
            <list-item>
              <p>&#8211; Como agentes de primeira linha para al&#237;vio sintom&#225;tico em pacientes com angina vasoesp&#225;stica. Grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
            <list-item>
              <p>&#8211; Em pacientes sintom&#225;ticos com angina est&#225;vel em uso de betabloqueadores (diidropirid&#237;nicos). Grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
            <list-item>
              <p>&#8211; Em pacientes sintom&#225;ticos com angina est&#225;vel em uso de betabloqueadores (verapamil ou diltiazem). Grau de recomenda&#231;&#227;o III, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
            <list-item>
              <p>&#8211; Em pacientes com angina est&#225;vel e contraindica&#231;&#227;o ao uso de betabloqueadores (preferencialmente verapamil ou diltiazem). Grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
            <list-item>
              <p>&#8211; Em pacientes com angina est&#225;vel sintom&#225;tica (diidropirid&#237;nicos de a&#231;&#227;o r&#225;pida). Grau de recomenda&#231;&#227;o III, n&#237;vel de evid&#234;ncia: B.</p>
            </list-item>
          </list>
          <p>
            <bold>c) Nitratos:</bold>
          </p>
          <list list-type="simple">
            <list-item>
              <p>&#8211; <bold>Nitratos de a&#231;&#227;o r&#225;pida:</bold> Para al&#237;vio sintom&#225;tico das crises agudas de angina. Grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
            <list-item>
              <p>&#8211; <bold>Nitratos de a&#231;&#227;o prolongada:</bold> o uso cont&#237;nuo de nitratos de a&#231;&#227;o prolongada induz &#224; toler&#226;ncia medicamentosa.</p>
            </list-item>
            <list-item>
              <p>&#8211; Agente de primeira linha em pacientes com angina est&#225;vel. Grau de recomenda&#231;&#227;o III, n&#237;vel de evid&#234;ncia C.</p>
            </list-item>
            <list-item>
              <p>&#8211; Agente de terceira linha em pacientes com angina est&#225;vel, que continuam sintom&#225;ticos mesmo ap&#243;s o uso de outros agentes antianginosos associados. Grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
            <list-item>
              <p>&#8211; Para al&#237;vio sintom&#225;tico em pacientes com angina vasoesp&#225;stica ap&#243;s o uso de bloqueadores dos canais de c&#225;lcio. Grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
          </list>
          <p><bold>d) Trimetazidina:</bold> subst&#226;ncia com efeitos metab&#243;licos e anti-isqu&#234;micos sem qualquer efeito na hemodin&#226;mica cardiovascular<xref ref-type="bibr" rid="B27">27</xref>.</p>
          <list list-type="simple">
            <list-item>
              <p>&#8211; Em pacientes sintom&#225;ticos com angina est&#225;vel em uso isolado ou associado de betabloqueadores a outros agentes antianginosos. Grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
            <list-item>
              <p>&#8211; Em pacientes com angina est&#225;vel e disfun&#231;&#227;o ventricular esquerda associada &#224; terapia otimizada. Grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
            <list-item>
              <p>&#8211; Em pacientes com angina est&#225;vel durante procedimentos de revasculariza&#231;&#227;o mioc&#225;rdica (percut&#226;nea ou cir&#250;rgica). Grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
          </list>
          <p><bold>e) Ivabradina:</bold> Inibidora espec&#237;fica da corrente I<sub><italic>f</italic></sub> no n&#243; sinusal, que reduz especificamente a frequ&#234;ncia card&#237;aca<xref ref-type="bibr" rid="B28">28</xref>.</p>
          <list list-type="simple">
            <list-item>
              <p>&#8211; Em pacientes sintom&#225;ticos com angina est&#225;vel, em uso de betabloqueadores isoladamente ou com outros agentes antianginosos, e frequ&#234;ncia card&#237;aca &gt; 70 bpm. Grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
            <list-item>
              <p>&#8211; Em pacientes sintom&#225;ticos com angina est&#225;vel, intolerantes a betabloqueadores isolados ou associados a outros agentes antianginosos. Grau de recomenda&#231;&#227;o IIb, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
            <list-item>
              <p>&#8211; Em pacientes com angina est&#225;vel, disfun&#231;&#227;o ventricular esquerda (FEVE &lt; 40%) e frequ&#234;ncia card&#237;aca &#8805; 70 bpm em terapia otimizada. Grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia B.</p>
            </list-item>
          </list>
          <p><bold>f) Ranolazina:</bold> derivado da piperazina. Semelhante &#224; trimetazidina, tamb&#233;m protege pacientes da isquemia por aumento do metabolismo da glicose e diminui&#231;&#227;o da oxida&#231;&#227;o de &#225;cidos graxos. Por&#233;m, seu maior efeito parece ser a inibi&#231;&#227;o da corrente tardia de s&#243;dio<xref ref-type="bibr" rid="B29">29</xref>.</p>
          <p>As <xref ref-type="fig" rid="f04">figuras 1</xref> e <xref ref-type="fig" rid="f05">2</xref> apresentam algoritmos que facilitam a compreens&#227;o das op&#231;&#245;es terap&#234;uticas medicamentosas na DAC est&#225;vel.</p>
          <fig id="f04">
            <label>Figura 1</label>
            <caption>
              <title>Algoritmo para tratamento medicamentoso da angina est&#225;vel com agentes antianginosos para al&#237;vio de sintomas e melhora na qualidade de vida. Detalhes, graus de recomenda&#231;&#227;o e n&#237;vel de evid&#234;ncia: vide texto correspondente.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-105-04-0328-50136-gf01-pt.jpg"/></fig>
          <fig id="f05">
            <label>Figura 2</label>
            <caption>
              <title>Algoritmo para redu&#231;&#227;o de eventos cardiovasculares na presen&#231;a de disfun&#231;&#227;o ventricular esquerda. Detalhes, graus de recomenda&#231;&#227;o e n&#237;vel de evid&#234;ncia: vide texto correspondente. AAS: &#193;cido acetilsalic&#237;lico; HA: Hipertens&#227;o arterial; iECA: Inibidores da enzima conversa de angiotensina; BRA: Bloqueador do receptor da angiotensina I; PA: Press&#227;o arterial; FC: Frequ&#234;ncia card&#237;aca.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-105-04-0328-50136-gf02-pt.jpg"/></fig>
        </sec>
      </sec>
      <sec>
        <title>Parte III &#8211; Tratamento com medidas invasivas</title>
        <sec>
          <title>Tratamento com medidas invasivas</title>
          <sec>
            <title>Cirurgia de revasculariza&#231;&#227;o direta</title>
            <p>As Diretrizes de Revasculariza&#231;&#227;o Mioc&#225;rdica<xref ref-type="bibr" rid="B30">30</xref> contemplam as t&#233;cnicas do procedimento, as alternativas e o que se pratica na atualidade, al&#233;m de revisar, sumariamente, estudos cl&#225;ssicos, comparando as estrat&#233;gias do tratamento cir&#250;rgico,<italic> o  </italic>tratamento cl&#237;nico e a Interven&#231;&#227;o Coron&#225;ria Percut&#226;nea (ICP).</p>
            <sec>
              <title>Principais indica&#231;&#245;es para a revasculariza&#231;&#227;o direta</title>
              <p>
                <bold>Grau de recomenda&#231;&#227;o I</bold>
              </p>
              <p>Estenose &#8805; 50% em tronco de coron&#225;ria esquerda ou em situa&#231;&#227;o equivalente (em art&#233;ria descendente anterior esquerda e art&#233;ria circunflexa esquerda no &#243;stio, ou anterior &#224; sa&#237;da de ramos importantes). N&#237;vel de evid&#234;ncia A.</p>
              <p>Estenoses proximais (&gt; 70%) nos tr&#234;s vasos principais, com ou sem envolvimento da art&#233;ria descendente anterior esquerda proximal, principalmente nos pacientes com fra&#231;&#227;o de eje&#231;&#227;o &lt; 50%, ou evid&#234;ncia funcional de isquemia moderada a grave. N&#237;vel de evid&#234;ncia B.</p>
              <p>Estenose em dois vasos principais, com les&#227;o proximal de art&#233;ria descendente anterior esquerda em pacientes com fra&#231;&#227;o de eje&#231;&#227;o &lt; 50%, ou evid&#234;ncia funcional de isquemia moderada a grave. N&#237;vel de evid&#234;ncia B.</p>
              <p>
                <bold>Grau de recomenda&#231;&#227;o IIa</bold>
              </p>
              <p>Utiliza&#231;&#227;o de enxerto arterial de mam&#225;ria esquerda para pacientes com estenose significativa (&gt; 70%) em art&#233;ria descendente anterior esquerda proximal e evid&#234;ncia de isquemia em territ&#243;rio extenso, visando &#224; melhora de sobrevida. N&#237;vel de evid&#234;ncia B.</p>
              <p>Realiza&#231;&#227;o de ponte de art&#233;ria coron&#225;ria em vez de interven&#231;&#227;o coron&#225;ria percut&#226;nea para pacientes com DAC multivascular e diabetes melitus, particularmente naqueles com utiliza&#231;&#227;o de enxerto arterial de mam&#225;ria esquerda para art&#233;ria descendente anterior esquerda. N&#237;vel de evid&#234;ncia B.</p>
              <p>
                <bold>Grau de recomenda&#231;&#227;o III</bold>
              </p>
              <p>Pacientes assintom&#225;ticos, com fun&#231;&#227;o ventricular normal, sem &#225;reas extensas de isquemia ou comprometimento proximal da art&#233;ria descendente anterior esquerda. N&#237;vel de evid&#234;ncia C.</p>
              <p>Pacientes assintom&#225;ticos sem les&#245;es anat&#244;micas (&lt; 70%, ou &lt; 50% no tronco de art&#233;ria coron&#225;ria esquerda) ou funcionais significativas (por exemplo: reserva fracionada de fluxo mioc&#225;rdico &gt; 0,8 ou isquemia discreta em provas n&#227;o invasivas) das art&#233;rias coron&#225;rias. N&#237;vel de evid&#234;ncia C.</p>
              <p>Uma ou duas art&#233;rias comprometidas, exceto art&#233;ria descendente anterior esquerda proximal, sem nenhuma &#225;rea importante de isquemia em teste funcional ou com irriga&#231;&#227;o de pequena &#225;rea de mioc&#225;rdio vi&#225;vel. N&#237;vel de evid&#234;ncia B.</p>
              <p>Les&#245;es moderadas (entre 50 a 60%), exceto no tronco de art&#233;ria coron&#225;ria esquerda, sem isquemia moderada demonstr&#225;vel em teste funcional.</p>
              <p>Les&#245;es insignificantes (&lt; 50%).</p>
            </sec>
            <sec>
              <title>Conceito "Time do Cora&#231;&#227;o" (<italic>Heart team</italic>) para revasculariza&#231;&#227;o mioc&#225;rdica</title>
              <sec>
                <title>
                  <underline>Classe I</underline>
                </title>
                <p>Uma equipe composta por cardiologista cl&#237;nico, cirurgi&#227;o e cardiologista intervencionista &#233; recomendada para individualizar a indica&#231;&#227;o de tratamento nos pacientes com les&#245;es de tronco de art&#233;ria coron&#225;ria esquerda ou DAC complexa: N&#237;vel de evid&#234;ncia C<xref ref-type="bibr" rid="B31">31</xref>.</p>
              </sec>
            </sec>
          </sec>
          <sec>
            <title>Revasculariza&#231;&#227;o por cateter: indica&#231;&#245;es cl&#237;nicas</title>
            <sec>
              <title>Revasculariza&#231;&#227;o vs. terapia medicamentosa (<xref ref-type="fig" rid="f06">Figura 3</xref>)</title>
              <fig id="f06">
                <label>Figura 3</label>
                <caption>
                  <title>Interven&#231;&#227;o coron&#225;ria percut&#226;nea (ICP) ou cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica (CRM) na doen&#231;a arterial coron&#225;ria est&#225;vel sem envolvimento do tronco da coron&#225;ria esquerda. <sup>a</sup>&#8805; 50% de estenose e comprova&#231;&#227;o de isquemia, les&#227;o &gt; 90% comprovada por dois m&#233;dicos, ou reserva de fluxo fracionada de 0,80; b CRM &#233; a op&#231;&#227;o preferida na maioria dos pacientes, a menos que eles apresentem comorbidades ou particularidades que demandem discuss&#227;o com a equipe cardiol&#243;gica (Heart team). Adaptado de: Orienta&#231;&#245;es da ESC/EACTS sobre Revasculariza&#231;&#227;o Mioc&#225;rdica de 2010.</title>
                </caption>
                <graphic xlink:href="1678-4170-abc-105-04-0328-50136-gf03-pt.jpg"/></fig>
              <sec>
                <title>Interven&#231;&#227;o coron&#225;ria percut&#226;nea vs. tratamento cl&#237;nico</title>
                <p>At&#233; o momento, nenhum estudo foi capaz de demonstrar que a interven&#231;&#227;o coron&#225;ria percut&#226;nea em pacientes com DAC est&#225;vel melhora as taxas de sobrevida<xref ref-type="bibr" rid="B32">32</xref>.</p>
              </sec>
              <sec>
                <title>Adequada utiliza&#231;&#227;o de revasculariza&#231;&#227;o</title>
                <sec>
                  <title>Pacientes com doen&#231;a triarterial</title>
                  <p>A ponte de art&#233;ria coron&#225;ria &#233; a estrat&#233;gia preferencial para pacientes com idade avan&#231;ada, baixa fra&#231;&#227;o de eje&#231;&#227;o, disfun&#231;&#227;o renal, doen&#231;a vascular perif&#233;rica, diabetes melitus ou   <italic>escore</italic> Syntax &gt; 22.</p>
                </sec>
              </sec>
            </sec>
          </sec>
        </sec>
        <sec>
          <title>Situa&#231;&#245;es especiais</title>
          <sec>
            <title>Pacientes diab&#233;ticos</title>
            <p>O diabetes mellitus &#233; condi&#231;&#227;o cl&#237;nica cada vez mais prevalente e associada a risco aumentado de complica&#231;&#245;es cardiovasculares, em especial a mortalidade tardia.</p>
            <sec>
              <title>Indica&#231;&#245;es para revasculariza&#231;&#227;o mioc&#225;rdica</title>
              <sec>
                <title>Compara&#231;&#227;o das estrat&#233;gias de revasculariza&#231;&#227;o em diab&#233;ticos com doen&#231;a coron&#225;ria multiarterial</title>
                <p>An&#225;lise de sensibilidade mostrou que a superioridade da ponte de art&#233;ria coron&#225;ria mioc&#225;rdica foi mais evidente em indiv&#237;duos com escore Syntax alto (&gt; 33), n&#227;o havendo diferen&#231;a estatisticamente significativa entre os grupos com escore baixo e intermedi&#225;rio<xref ref-type="bibr" rid="B33">33</xref>.</p>
              </sec>
              <sec>
                <title>Aspectos da interven&#231;&#227;o coron&#225;ria percut&#226;nea em diab&#233;ticos</title>
                <p><italic>Stents</italic> farmacol&#243;gicos s&#227;o recomendados para reduzir a reestenose e a necessidade de nova revasculariza&#231;&#227;o do vaso-alvo<xref ref-type="bibr" rid="B34">34</xref><sup>,</sup><xref ref-type="bibr" rid="B35">35</xref>.</p>
                <p>A terap&#234;utica antiplaquet&#225;ria dupla com AAS e um bloqueador do receptor P2Y12 &#233; componente essencial dos regimes farmacol&#243;gicos durante e ap&#243;s o procedimento. Pacientes que recebem <italic>stents</italic>farmacol&#243;gicos devem utiliz&#225;&#8209;la por 12 meses e os que recebem <italic>stents</italic>n&#227;o farmacol&#243;gicos devem utiliz&#225;-la por 1 m&#234;s.</p>
              </sec>
            </sec>
            <sec>
              <title>Pacientes com revasculariza&#231;&#227;o pregressa</title>
              <p>As principais indica&#231;&#245;es para revasculariza&#231;&#227;o s&#227;o persist&#234;ncia dos sintomas, independentemente de terapia otimizada e/ou progn&#243;stico.</p>
            </sec>
          </sec>
        </sec>
      </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>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
