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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">Zjwhb3sjkn6rzLPbWgVW8wv</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2018001800856</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20180207</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Viewpoint</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Sudden Death in Young Brazilian Athletes: Isn't It Time We Created a Genuinely National Register?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Helal</surname>
            <given-names>Lucas</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ferrari</surname>
            <given-names>Filipe</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Stein</surname>
            <given-names>Ricardo</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
          <xref ref-type="aff" rid="aff3">3</xref>
          <xref ref-type="aff" rid="aff4">4</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Universidade Federal do Rio Grande do Sul</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Programa de P&#243;s-gradua&#231;&#227;o em Cardiologia e Ci&#234;ncias Cardiovasculares</institution>
        <addr-line>
          <city>Porto Alegre</city>
          <state>RS</state>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Programa de P&#243;s-gradua&#231;&#227;o em Cardiologia e Ci&#234;ncias Cardiovasculares da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS - Brasil</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Hospital de Cl&#237;nicas de Porto Alegre</institution>
        <institution content-type="orgdiv1">Laborat&#243;rio de Fisiopatologia do Exerc&#237;cio</institution>
        <addr-line>
          <city>Porto Alegre</city>
          <state>RS</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Laborat&#243;rio de Fisiopatologia do Exerc&#237;cio, Hospital de Cl&#237;nicas de Porto Alegre, Porto Alegre, RS - Brazil</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Hospital de Cl&#237;nicas de Porto Alegre</institution>
        <institution content-type="orgdiv1">Grupo de Pesquisa em Cardiologia do Exerc&#237;cio</institution>
        <addr-line>
          <city>Porto Alegre</city>
          <state>RS</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Grupo de Pesquisa em Cardiologia do Exerc&#237;cio, Hospital de Cl&#237;nicas de Porto Alegre, Porto Alegre, RS - Brazil</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgname">Universidade Federal do Rio Grande do Sul</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Departamento de Medicina Interna</institution>
        <addr-line>
          <city>Porto Alegre</city>
          <state>RS</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Departamento de Medicina Interna da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Ricardo Stein</bold> Jo&#227;o Caetano, 20/402. Postal Code 90470-260, Petr&#243;polis, Porto Alegre, RS - Brazil E-mail: <email>rstein@cardiol.br</email>, <email>kuqui.r@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research; Acquisition of data; Analysis and interpretation of the data; Statistical analysis; Obtaining financing; Writing of the manuscript and Critical revision of the manuscript for intellectual content: Helal L, Ferrari F, Stein R.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <month>12</month>
        <year>2018</year>
      </pub-date>
      <volume>111</volume>
      <issue>6</issue>
      <fpage>856</fpage>
      <lpage>859</lpage>
      <history>
        <date date-type="received">
          <day>16</day>
          <month>04</month>
          <year>2018</year>
        </date>
        <date date-type="rev-recd">
          <day>12</day>
          <month>06</month>
          <year>2018</year>
        </date>
        <date date-type="accepted">
          <day>12</day>
          <month>06</month>
          <year>2018</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <p>Young competitive athletes (&#8804; 35 years old) with or without a previous diagnosis of cardiovascular disease may suddenly die in competitive activities, potentially leading to an impact in society through the media. Although the relative risk for sudden death (SD) in athletes is twice as high as for their counterparts, the absolute incidence is low. While there is consensus among medical societies worldwide that early detection of causal factors is highly desirable, there is debate among different screening schemes to that end. In Brazil, the recommendations of the Brazilian Society of Cardiology mirror the guidelines of the European Society of Cardiology (ESC), which indicate a clinical examination combined with a 12-lead resting electrocardiogram, regardless of the presence of risk factors. The possibility of genetic screening is also plausible, since most clinical entities that cause SD in young competitive athletes are related to genotype. Finally, considering the diversity of practiced sports, and the population miscegenation, we emphasize the need to a national registry of cases.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Cardiovascular Diseases</kwd>
        <kwd>Athletes</kwd>
        <kwd>Adolescent</kwd>
        <kwd>Youth Sports</kwd>
        <kwd>Death, Sudden, Cardiac</kwd>
        <kwd>Genotype</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Sudden death (SD) in young athletes (under 35 years old) is a peculiar event. Despite being rare, cases have been reported by far-reaching media, which may cause a major impact on both health agencies and the society. The counterintuitive feeling that young, presumably asymptomatic individuals with above-average physical fitness may die suddenly during sports practice seems particularly striking to many people, especially when it affects elite athletes.</p>
      <p>People involved in intense competitive activities have a relative SD risk that is nearly twice as high as that of their non-athlete counterparts, though incidence in absolute numbers is very low - 0.5 to 2 events per 100,000 athletes per year.<xref ref-type="bibr" rid="B1">1</xref> Usually, clinical entities of cardiac or vascular nature, whether previously diagnosed or not, are the most prevalent causes of SD, and participation in sports events one of is the triggering factor for its occurrence. The most frequent are of genetic origin and hereditary, whether they structural (e.g., myocardiopathies) or not (e.g., channelopathies). On the other hand, the aortic (e.g., Marfan Syndrome) and coronary artery diseases are less prevalent but have also been described in this age group.<xref ref-type="bibr" rid="B2">2</xref> Based on evidence unrelated to exercise, external causal factors can also be considered. For example, the use of central nervous system stimulant drugs and anabolic steroids seems to increase the risk of SD in adults,<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> so it is plausible to hypothesize that athletes exposed to these risk factors may add to that statistic.</p>
      <p>In relation to its prevention, some success rate can be achieved if the disease is detected in time. There is treatment available for some illnesses and, on certain occasions, there may be a medical decision to suspend the athlete's participation in competitive sport (disqualification), thereby protecting them. Therefore, whenever possible, early detection of triggering diseases should be made. However, medical societies in various countries recommend different screening schemes.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> Since the etiology of causative factors can differ regarding geography, ethnicity, sporting modality, genetic inheritance, and age, this point-of-view article aims to discuss the need for a national register of cases so the best prevention and early detection strategy may be laid out in Brazil - an idea already mentioned in this journal seven years ago.<xref ref-type="bibr" rid="B7">7</xref>
			</p>
      <sec>
        <title>Screening Schemes Suggested and the Absence of a Brazilian Register</title>
        <p>In 2011, Peidro, Froelicher and Stein published a point of view discussing particularities of Pre-Participation Physical Examination (PPE) for SD prevention in young athletes in Argentina and Brazil.<xref ref-type="bibr" rid="B7">7</xref> At the time, given the experiences that the American and Italian communities had about the effectiveness of the different decision algorithms, the need for national registers (in Argentina and Brazil) for SD cases was suggested. Since then, little has been done, and the national recommendation is not based on local data or robust evidence, such as: a) the prevalence of SD and its causes; b) ideally, subsequent evaluation of the effectiveness of potential screening strategies by means of randomized clinical trials; c) health technology assessment the algorithm to be proposed.</p>
        <p>The Brazilian Society of Cardiology (SBC) and the Brazilian Society of Exercise and Sports Medicine (SBMEE) jointly recommend the same screening scheme as the European Society of Cardiology (ESC)<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref> - i.e., anamnesis, physical examination and 12-lead resting electrocardiogram (ECG), regardless of the presence or absence of risk factors. The scheme proposed by the ESC is heavily influenced by observational evidence collected in Italy. Initially, it was found that young athletes from the Veneto region were at high risk of SD during competitive sports practice, compared to other regions of the world.<xref ref-type="bibr" rid="B9">9</xref> In 2006, Corrado et al.<xref ref-type="bibr" rid="B10">10</xref> highlighted a high prevalence of Arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypothesized that disqualifying athletes with a diagnosis or suspicion of that disease (or similar diseases) would be effective to reduce SD mortality at sports events.<xref ref-type="bibr" rid="B10">10</xref> These findings increased the discussion on the implementation of a specific algorithm that would make ECG mandatory in addition to anamnesis and physical examination as screening procedures for anyone engaging in a competitive and structured physical exercise program. Two years later and criticism aside, a classic study published by the same group of researchers tested the scheme and demonstrated it reduced SD cases by 89% in competitive activities involving young athletes in that country.<xref ref-type="bibr" rid="B11">11</xref> In fact, the PPE has been mandatory for more than two decades for every regulated amateur or professional athlete, with an Italian federal law that is adopted by all sports regulation entities.<xref ref-type="bibr" rid="B12">12</xref>
				</p>
        <p>On the other hand, the joint procedure recommended by the American College of Cardiology (ACC) and the American College of Sports Medicine (ACSM) do not include a mandatory ECG, as argue that the annual incidence of SD in the United States is much lower than in Italy.<xref ref-type="bibr" rid="B5">5</xref> In addition, they reiterate that ECG's sub-optimal specificity for detecting anomalies in athletes may result in an excessive number of false-positive results.</p>
        <p>In this regard, the overall consequences of a false-positive result<xref ref-type="bibr" rid="B13">13</xref> may lead to unnecessary over-investigation (e.g., echocardiography, cardiac resonance, among other examinations), with undesired financial and personal costs, or even disqualifications. However, contrary to the arguments of the American entities above, a cost-effectiveness analysis conducted by a Stanford group<xref ref-type="bibr" rid="B14">14</xref> pointed out that including ECG in the clinical examination would prevent 2.09 additional deaths per 1,000 athletes, with an estimated individual cost of U$ 89 per examination and a cost-effectiveness estimate of approximately U$ 43,000 per qualitiy-adjusted life years (QALY).</p>
        <p>For Brazil, these data are particularly important, since the Ministry of Health is currently discussing, together with the National Congress and academic entities involved in the assessment of health technologies, the threshold of willingness to pay for added technology. Because until the present the cost per QALY of a new technology is unknown, we believe it is critical that decisions be made in Brazil based on knowledge of local statistics, which again reinforces the need for a national register of SD in young athletes to be properly conducted.</p>
      </sec>
      <sec>
        <title>Why a National Register is Necessary</title>
        <p>Because the etiology of SD in sports in young athletes is diverse, with regional and genetic influences, identifying the local prevalence is of utmost importance to make decisions based on evidence. For example, ethnicity has an effect on the incidence of SD in young athletes. In the US, an increased incidence of SD was found in black basketball and football players compared with other ethnic groups, most often due to hypertrophic cardiomyopathy (HCM).<xref ref-type="bibr" rid="B15">15</xref> Autopsy data from that country showed that that twice as many black athletes died from HCM as white athletes (20% vs. 10%).<xref ref-type="bibr" rid="B16">16</xref> Such information suggests a possible divergence in HCM presentation in different ethnic groups and that it may be more malignant in black individuals.</p>
        <p>In fact, in at least 50% of the cases, HCM presents as an autosomal dominant monogenic disease. Its overall prevalence is traditionally estimated at 1:500 individuals,<xref ref-type="bibr" rid="B17">17</xref> but more recent data indicate that it may be even more frequent than previously established, which is corroborated by advances in genetic research.<xref ref-type="bibr" rid="B18">18</xref> In Brazil, the frequency of HCM is not solidly known. Here, it is our opinion that this disease is an example of the importance of ECG in the context of competitive athletes, as it can be suspected through this examination in a high percentage of cases. Moreover, changes in the ST segment, in the T wave, as well as the presence of pathological Q waves<xref ref-type="bibr" rid="B19">19</xref> can be warning signs based on which further exams (with a higher positive predictive value) can be requested in a context of greater pretest probability.</p>
        <p>Once there is a diagnosis (clinical and/or molecular), septal ablation, myectomy, and/or an implantable cardioverter defibrillator (ICD) may be indicated. Likewise, but only in well-selected cases, disqualification may be the final outcome for the athlete's career.<xref ref-type="bibr" rid="B20">20</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref> In respect to the ethnicity of the Brazilian population, which is extremely mixed and with a high prevalence of blacks,<xref ref-type="bibr" rid="B22">22</xref> knowing the causes of SD in Brazilian athletes of this race seems to us very important to classify the risk for these individuals.</p>
        <p>As for the causes of SD due to ion channel disturbance, genetic screening,<xref ref-type="bibr" rid="B23">23</xref> already included in the SBC's 2013 guidelines,<xref ref-type="bibr" rid="B8">8</xref> has been suggested as a possible strategy to help with prevention (note of the authors: when properly indicated), given the high contribution of the genetic factor for the event's occurrence.<xref ref-type="bibr" rid="B24">24</xref> given the high contribution of the genetic factor for the event's occurrence.<xref ref-type="bibr" rid="B24">24</xref> In fact, some malignant mutations are already known in genes that cause Long QT Syndrome (LQTS), Short QT Syndrome, Brugada Syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT).<xref ref-type="bibr" rid="B25">25</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref> Here, we would like to point out that although molecular mapping is accessible and technical improvement through new generation sequencing is available in our country, requesting it is still not part of our medical culture, even in more robust clinical scenarios (e.g., breast neoplasm screening and association with BRCA genes).<xref ref-type="bibr" rid="B27">27</xref> In fact, in order for medical entities to formally encourage its request in PPE, it is necessary to know prevalence so that the technology can be submitted to the health technology assessment (HTA) process, which is similar to the processes already performed for other clinical entities.<xref ref-type="bibr" rid="B28">28</xref>
				</p>
        <p>The sport modality also has some bearing on the construction of a decision algorithm for PPE and SD prevention in young athletes. For example, in the United States, SD prevalence is higher in basketball and football.<xref ref-type="bibr" rid="B29">29</xref> In Europe, SD in young athletes is more frequent in field soccer players.<xref ref-type="bibr" rid="B30">30</xref> As a matter of curiosity, in combat sports, which involve high-energy trauma, or in sports involving interaction with high-speed artifacts (e.g., baseball), concerns with commotio cordis (a malignant arrhythmia triggered by direct trauma in the anterior thorax) must be present.<xref ref-type="bibr" rid="B31">31</xref>
				</p>
      </sec>
      <sec>
        <title>Future Directions</title>
        <p>As exposed above, we identified a few points still unknown which require priority examination in order to define tracking, prevention and national regulation strategies, all of which are essential for the HTA process; and which can be accessed through a genuinely Brazilian register (<xref ref-type="fig" rid="f1">Figure 1</xref>).</p>
        <p>
          <fig id="f1">
            <label>Figure 1</label>
            <caption>
              <title>Suggestion of statistics to be surveyed by means of a national register of SD cases in competitive sports in young athletes. SD: sudden death.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-111-06-0856-80207-gf01.jpg"/></fig>
        </p>
        <p>We emphasize the central role of public research support agencies in Brazil for building a register. A call for projects specifically to that end seems to us appropriate, preferably for projects of a multicentric nature and with public sharing of data. So far, considering the lack interest on the part of independent researchers, the State has not yet expressed a position, nor has it facilitated the implementation of a viable strategy for a national register, which we consider a critical step.</p>
      </sec>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>Lucas Helal has full-time research support by CAPES. Ricardo Stein is an estabilished CNPq researcher.</p>
      </fn>
    </fn-group>
    <fn-group>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This article is part of the master's thesis submitted by Filipe Ferrari, from the Graduate Program in Cardiology and Cardiovascular Sciences of the Faculty of Medicine of the Universidade Federal do Rio Grande do Sul.</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Ponto de Vista</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Morte S&#250;bita no Atleta Jovem Brasileiro: N&#227;o Ser&#225; Hora de Criarmos um Registro Genuinamente Nacional?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Helal</surname>
            <given-names>Lucas</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ferrari</surname>
            <given-names>Filipe</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
          <xref ref-type="aff" rid="aff7">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Stein</surname>
            <given-names>Ricardo</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
          <xref ref-type="aff" rid="aff7">3</xref>
          <xref ref-type="aff" rid="aff8">4</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
      </contrib-group>
      <aff id="aff5">
        <label>1</label>
        <institution content-type="original">Programa de P&#243;s-gradua&#231;&#227;o em Cardiologia e Ci&#234;ncias Cardiovasculares da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS - Brasil</institution>
      </aff>
      <aff id="aff6">
        <label>2</label>
        <institution content-type="original">Laborat&#243;rio de Fisiopatologia do Exerc&#237;cio, Hospital de Cl&#237;nicas de Porto Alegre, Porto Alegre, RS - Brasil</institution>
      </aff>
      <aff id="aff7">
        <label>3</label>
        <institution content-type="original">Grupo de Pesquisa em Cardiologia do Exerc&#237;cio, Hospital de Cl&#237;nicas de Porto Alegre, Porto Alegre, RS - Brasil</institution>
      </aff>
      <aff id="aff8">
        <label>4</label>
        <institution content-type="original">Departamento de Medicina Interna da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS - Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Ricardo Stein</bold> Jo&#227;o Caetano, 20/402. CEP 90470-260, Petr&#243;polis, Porto Alegre, RS - Brasil E-mail: <email>rstein@cardiol.br</email>, <email>kuqui.r@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa; Obten&#231;&#227;o de dados; An&#225;lise e interpreta&#231;&#227;o dos dados; An&#225;lise estat&#237;stica; Obten&#231;&#227;o de financiamento; Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Helal L, Ferrari F, Stein R.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesses</bold>
          </p>
          <p>Os autores declaram n&#227;o haver conflito de interesses de nenhuma origem pertinentes a esse trabalho.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <p>Atletas jovens (&#8804; 35 anos), com doen&#231;as cardiovasculares de diagn&#243;stico conhecido ou n&#227;o, podem morrer subitamente em atividades competitivas, fato este que pode causar grande impacto na m&#237;dia e na sociedade. Embora apresentem risco relativo aproximadamente duas vezes maior em compara&#231;&#227;o com seus pares n&#227;o-atletas, a incid&#234;ncia absoluta de morte s&#250;bita (MS) &#233; baixa. Entre entidades m&#233;dicas no mundo todo, &#233; consenso que a detec&#231;&#227;o precoce dos fatores causais &#233; muito desej&#225;vel, mas h&#225; debate em rela&#231;&#227;o aos diferentes esquemas de rastreamento para esse fim. No Brasil, a recomenda&#231;&#227;o da Sociedade Brasileira de Cardiologia espelha-se nas diretrizes da <italic>European Society of Cardiology</italic> (ESC), segundo as quais o exame cl&#237;nico aliado a um eletrocardiograma de repouso de 12 deriva&#231;&#245;es &#233; indicado, independentemente da presen&#231;a de fatores de risco. A possibilidade de rastreamento gen&#233;tico tamb&#233;m existe, uma vez que a maior parte das entidades cl&#237;nicas causadoras de MS no esporte em jovens atletas se relaciona com o gen&#243;tipo. Por fim, considerando a diversidade de modalidades esportivas praticadas, e sendo a popula&#231;&#227;o brasileira muito miscigenada, salientamos a necessidade de um registro nacional de casos.</p>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Doen&#231;as Cardiovasculares</kwd>
        <kwd>Atletas</kwd>
        <kwd>Adolescente</kwd>
        <kwd>Esportes Juvenis</kwd>
        <kwd>Morte S&#250;bita Card&#237;aca</kwd>
        <kwd>Gen&#243;tipo</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A morte s&#250;bita (MS) em atletas jovens (com menos de 35 anos) &#233; um evento peculiar. Muito embora de rara frequ&#234;ncia, casos t&#234;m sido divulgados pela m&#237;dia de grande alcance, e isso tem o potencial de promover impacto, tanto nos &#243;rg&#227;os de sa&#250;de quanto na sociedade civil. O sentimento contra-intuitivo de que indiv&#237;duos jovens, presumivelmente assintom&#225;ticos e com aptid&#227;o f&#237;sica acima da m&#233;dia possam morrer subitamente durante a pr&#225;tica esportiva tem uma poderosa penetra&#231;&#227;o social, sobretudo quando s&#227;o afetados atletas de elite.</p>
        <p>Pessoas envolvidas em atividades competitivas intensas t&#234;m risco relativo de MS quase duas vezes maior que seus pares de mesma idade e n&#227;o-atletas, embora a incid&#234;ncia absoluta seja muito baixa - 0,5 a 2 eventos/100.000 atletas/ano.<xref ref-type="bibr" rid="B1">1</xref> Usualmente, entidades cl&#237;nicas card&#237;acas ou vasculares, de diagn&#243;stico conhecido ou n&#227;o, s&#227;o as causas de MS mais prevalentes, sendo a participa&#231;&#227;o em eventos esportivos o fator desencadeador da sua ocorr&#234;ncia. As mais frequentes s&#227;o de origem gen&#233;tica e de car&#225;ter heredit&#225;rio, podendo ser estruturais (e.g., miocardiopatias) ou n&#227;o (e.g., canalopatias). Por outro lado, as doen&#231;as da aorta (e.g. S&#237;ndrome de Marfan) e a doen&#231;a arterial coronariana s&#227;o menos prevalentes, mas tamb&#233;m t&#234;m sido descritas nesta faixa et&#225;ria.<xref ref-type="bibr" rid="B2">2</xref> A partir de evid&#234;ncias n&#227;o relacionadas ao exerc&#237;cio, fatores causais externos tamb&#233;m podem ser cogitados. Por exemplo, o uso de drogas estimulantes do sistema nervoso central e de esteroides anabolizantes parece aumentar o risco de MS em adultos,<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> sendo plaus&#237;vel levantar a hip&#243;tese de que atletas expostos a estes fatores de risco possam incrementar tal estat&#237;stica.</p>
        <p>Em rela&#231;&#227;o &#224; sua preven&#231;&#227;o, alguma taxa de sucesso pode ser alcan&#231;ada se a doen&#231;a for detectada em tempo. Algumas enfermidades t&#234;m tratamento dispon&#237;vel e, em certas ocasi&#245;es, pode haver decis&#227;o m&#233;dica de suspender a participa&#231;&#227;o do atleta no esporte competitivo (desqualifica&#231;&#227;o), oferecendo-lhe prote&#231;&#227;o. Por isso, sempre que poss&#237;vel, a detec&#231;&#227;o precoce de tais doen&#231;as deve ser realizada. No entanto, as sociedades m&#233;dicas de pa&#237;ses diversos recomendam esquemas de rastreamento distintos.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> Uma vez que a etiologia dos fatores causadores pode variar conforme a geografia, etnia, modalidade esportiva, heran&#231;a gen&#233;tica e idade, este ponto de vista visa a discutir a necessidade de um registro nacional de casos, para que a melhor estrat&#233;gia de preven&#231;&#227;o e detec&#231;&#227;o precoce possa ser tra&#231;ada no Brasil - uma ideia j&#225; mencionada h&#225; sete anos neste mesmo peri&#243;dico.<xref ref-type="bibr" rid="B7">7</xref>
				</p>
        <sec>
          <title>Esquemas de rastreamento propostos e a aus&#234;ncia de um registro brasileiro</title>
          <p>Em 2011, Peidro, Froelicher e Stein publicaram um ponto de vista discutindo particularidades de exames pr&#233;-participa&#231;&#227;o (EPP) para preven&#231;&#227;o de MS em atletas jovens na Argentina e no Brasil.<xref ref-type="bibr" rid="B7">7</xref> Naquele momento, frente &#224;s experi&#234;ncias vividas pelas comunidades americana e italiana em rela&#231;&#227;o &#224; efetividade dos diferentes algoritmos de decis&#227;o, foi sugerida a necessidade de registros nacionais (Argentina e Brasil) para casos de MS. Desde ent&#227;o, muito pouco foi realizado, e a recomenda&#231;&#227;o nacional n&#227;o &#233; feita com base em dados locais, nem com evid&#234;ncias robustas, quais sejam: a) identifica&#231;&#227;o da preval&#234;ncia de MS e suas causas; b) idealmente, posterior avalia&#231;&#227;o da efic&#225;cia de poss&#237;veis estrat&#233;gias de rastreamento, por meio de ensaios cl&#237;nicos randomizados; c) avalia&#231;&#227;o da tecnologia em sa&#250;de (ATS) do esquema a ser proposto.</p>
          <p>A Sociedade Brasileira de Cardiologia (SBC) e a Sociedade Brasileira de Medicina do Exerc&#237;cio e do Esporte (SBMEE) recomendam, conjuntamente, o mesmo esquema de rastreamento que a <italic>European Society of Cardiology</italic> (ESC):<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref> anamnese, exame f&#237;sico e eletrocardiograma de repouso de 12 deriva&#231;&#245;es (ECG), independentemente da presen&#231;a ou n&#227;o de fatores de risco. O esquema proposto pela ESC &#233; fortemente influenciado pelas evid&#234;ncias observacionais produzidas na It&#225;lia. Inicialmente, foi verificado que jovens atletas da regi&#227;o do V&#234;neto, em compara&#231;&#227;o com outras regi&#245;es do mundo, apresentavam risco elevado de MS durante a pr&#225;tica esportiva competitiva.<xref ref-type="bibr" rid="B9">9</xref> Em 2006, Corrado et al.,<xref ref-type="bibr" rid="B10">10</xref> destacaram, nessa regi&#227;o, a alta preval&#234;ncia de displasia arritmog&#234;nica do ventr&#237;culo direito (DAVD), e levantaram a hip&#243;tese de que desqualificar atletas com seu diagn&#243;stico ou suspeita (ou de doen&#231;as semelhantes) seria eficaz em reduzir mortalidade por MS em eventos esportivos.<xref ref-type="bibr" rid="B10">10</xref> Tais achados intensificaram a discuss&#227;o sobre a implementa&#231;&#227;o de um esquema espec&#237;fico, que tornaria obrigat&#243;rio o ECG, juntamente com a anamnese e o exame f&#237;sico, no rastreamento de qualquer pessoa a se engajar em um programa de exerc&#237;cio f&#237;sico competitivo e estruturado. Dois anos depois e cr&#237;ticas &#224; parte, atrav&#233;s de publica&#231;&#227;o cl&#225;ssica do mesmo grupo de pesquisadores, o esquema foi testado e demonstrou redu&#231;&#227;o de 89% dos casos de MS em atividades competitivas envolvendo atletas jovens naquele pa&#237;s.<xref ref-type="bibr" rid="B11">11</xref> Por sinal, h&#225; mais de duas d&#233;cadas o EPP &#233; obrigat&#243;rio para todo atleta amador ou profissional regulamentado na It&#225;lia, sendo que uma lei federal rege todas as entidades esportivas regulat&#243;rias.<xref ref-type="bibr" rid="B12">12</xref>
					</p>
          <p>Por outro lado, a conduta conjunta recomendada pelo <italic>American College of Cardiology</italic> (ACC) e pelo <italic>American College of Sports Medicine</italic> (ACSM) retira a obrigatoriedade do ECG, sob o argumento de que a incid&#234;ncia anual de MS nos Estados Unidos (EUA) seria muito menor do que a verificada na It&#225;lia.<xref ref-type="bibr" rid="B5">5</xref> Al&#233;m disso, reiteram que a especificidade sub&#243;tima do ECG para detectar anomalias em atletas pode resultar em um n&#250;mero muito elevado de resultados falsos-positivos. Nesse particular, as consequ&#234;ncias globais de um resultado falso-positivo<xref ref-type="bibr" rid="B13">13</xref> podem culminar em investiga&#231;&#227;o excessiva (e.g., ecocardiograma, resson&#226;ncia card&#237;aca, entre outros exames), gerando custos financeiros e pessoais indesej&#225;veis; ou mesmo desqualifica&#231;&#227;o inapropriada. No entanto, indo de encontro &#224; sustenta&#231;&#227;o das entidades americanas supracitadas, uma an&#225;lise de custo-efetividade feita por um grupo de Stanford<xref ref-type="bibr" rid="B14">14</xref> apontou que a inclus&#227;o do ECG ao exame cl&#237;nico preveniria 2,09 mortes adicionais para cada 1000 atletas, com custo individual estimado de 89 d&#243;lares americanos por exame e estimativa de custo-efetividade de aproximadamente 43 mil d&#243;lares por anos ajustados por qualidade (QALY).</p>
          <p>Para o Brasil, estes dados s&#227;o particularmente importantes, uma vez que, neste exato momento, o Minist&#233;rio da Sa&#250;de discute, tanto junto ao Congresso Nacional quanto &#224;s entidades acad&#234;micas que realizam ATS, o limiar de disposi&#231;&#227;o a pagar por tecnologia adicionada. N&#227;o se sabendo, at&#233; o momento, qu&#227;o acomod&#225;vel ao or&#231;amento p&#250;blico &#233; o custo de adi&#231;&#227;o de uma tecnologia em sa&#250;de a ser ofertada por QALY, parece-nos muito importante que a tomada de decis&#227;o no Brasil seja feita com base no conhecimento das estat&#237;sticas locais, o que, novamente, evidencia a necessidade de um registro nacional de MS em jovens atletas adequadamente conduzido.</p>
        </sec>
        <sec>
          <title>Porque um registro nacional &#233; necess&#225;rio</title>
          <p>Dado que a etiologia da MS no esporte em jovens atletas &#233; diversa, com influ&#234;ncia regional e gen&#233;tica, a identifica&#231;&#227;o das preval&#234;ncias locais &#233; de suma import&#226;ncia para a tomada de decis&#227;o com base em evid&#234;ncias. Por exemplo, a etnia tem influ&#234;ncia sobre a incid&#234;ncia de MS em jovens atletas. Nos EUA, em atletas negros de ligas de basquetebol e futebol americano, verificou-se incid&#234;ncia aumentada de MS em rela&#231;&#227;o a outros estratos &#233;tnicos, tendo como causa, no mais das vezes, a miocardiopatia hipertr&#243;fica (MCH).<xref ref-type="bibr" rid="B15">15</xref> Dados de aut&#243;psias realizadas naquele pa&#237;s mostraram que atletas negros morreram duas vezes mais por MCH do que atletas brancos (20% <italic>vs.</italic> 10%).<xref ref-type="bibr" rid="B16">16</xref> Tais informa&#231;&#245;es permitem supor uma poss&#237;vel diverg&#234;ncia no quadro de apresenta&#231;&#227;o da MCH em diferentes etnias, podendo ser mais maligna em indiv&#237;duos negros.</p>
          <p>Por sinal, em pelo menos 50% das vezes, a MCH se apresenta como uma doen&#231;a autoss&#244;mica dominante monog&#234;nica. Sua preval&#234;ncia global &#233; tradicionalmente estimada em 1:500 indiv&#237;duos,<xref ref-type="bibr" rid="B17">17</xref> mas dados mais recentes apontam que ela pode ser ainda mais frequente do que o estabelecido no passado, e tais dados s&#227;o corroborados pelos avan&#231;os da pesquisa gen&#233;tica.<xref ref-type="bibr" rid="B18">18</xref> No Brasil, a frequ&#234;ncia da MCH n&#227;o &#233; solidamente conhecida. Nesse particular, &#233; nossa opini&#227;o que essa enfermidade serve como um exemplo da import&#226;ncia do ECG no cen&#225;rio do atleta competitivo, uma vez que a suspeita dessa doen&#231;a pode surgir atrav&#233;s desse exame em um percentual elevado dos casos. Ali&#225;s, altera&#231;&#245;es no segmento ST, na onda T, assim como a presen&#231;a de ondas Q patol&#243;gicas,<xref ref-type="bibr" rid="B19">19</xref> servem como sinais de alerta e, a partir disso, exames mais elaborados (de maior valor preditivo positivo) podem ser solicitados em um cen&#225;rio de maior probabilidade diagn&#243;stica pr&#233;-teste.</p>
          <p>Quando do diagn&#243;stico (cl&#237;nico e/ou molecular), a abla&#231;&#227;o septal, a miectomia, e/ou a disponibiliza&#231;&#227;o de um cardiodesfibrilador implant&#225;vel (CDI) podem ser indicados. Da mesma forma, mas somente em casos bem selecionados, o afastamento de atividades competitivas pode ser o desfecho final para carreira do atleta.<xref ref-type="bibr" rid="B20">20</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref> No que diz respeito &#224; etnia da popula&#231;&#227;o brasileira, a qual &#233; extremamente miscigenada e com grande preval&#234;ncia de negros,<xref ref-type="bibr" rid="B22">22</xref> o conhecimento de causas de MS em atletas brasileiros dessa ra&#231;a nos parece muito importante para a estratifica&#231;&#227;o do risco desses indiv&#237;duos.</p>
          <p>Em rela&#231;&#227;o &#224;s causas de MS por dist&#250;rbios nos canais i&#244;nicos, o rastreamento gen&#233;tico,<xref ref-type="bibr" rid="B23">23</xref> j&#225; levantado pela diretriz da SBC de 2013,<xref ref-type="bibr" rid="B8">8</xref> tem sido sugerido como estrat&#233;gia poss&#237;vel para auxiliar na preven&#231;&#227;o (nota dos autores: quando bem indicada), dada a alta contribui&#231;&#227;o do fator gen&#233;tico para a ocorr&#234;ncia do evento.<xref ref-type="bibr" rid="B24">24</xref> Por sinal, algumas muta&#231;&#245;es malignas j&#225; s&#227;o conhecidas em genes causadores da S&#237;ndrome do QT longo (SQTL), S&#237;ndrome do QT curto, S&#237;ndrome de Brugada e na taquicardia ventricular polim&#243;rfica catecolamin&#233;rgica (TVPC).<xref ref-type="bibr" rid="B25">25</xref><sup>,</sup><xref ref-type="bibr" rid="B26">26</xref> Aqui, gostar&#237;amos de salientar que, por mais que o mapeamento molecular esteja acess&#237;vel e o aprimoramento t&#233;cnico atrav&#233;s do sequenciamento de nova gera&#231;&#227;o seja uma realidade em nosso pa&#237;s, ainda n&#227;o existe uma cultura m&#233;dica para sua solicita&#231;&#227;o, mesmo em cen&#225;rios cl&#237;nicos mais s&#243;lidos (e.g., rastreamento para neoplasia mam&#225;ria e a associa&#231;&#227;o com genes da linhagem BRCA).<xref ref-type="bibr" rid="B27">27</xref> Ali&#225;s, para que ela seja formalmente estimulada no EPP por entidades m&#233;dicas, o conhecimento das preval&#234;ncias torna-se necess&#225;rio, a fim de que a tecnologia seja submetida ao processo de ATS, o qual &#233; semelhante aos j&#225; realizados para outras entidades cl&#237;nicas.<xref ref-type="bibr" rid="B28">28</xref>
					</p>
          <p>A modalidade esportiva praticada tamb&#233;m tem peso sobre a constru&#231;&#227;o de um algoritmo de decis&#227;o para EPP e preven&#231;&#227;o de MS em jovens atletas. Por exemplo, nos Estados Unidos a preval&#234;ncia de MS &#233; maior no basquetebol e no futebol americano.<xref ref-type="bibr" rid="B29">29</xref> Por sua vez, na Europa, a MS em atletas jovens &#233; mais frequente no futebol de campo.<xref ref-type="bibr" rid="B30">30</xref> Como curiosidade, em esportes de combate (que envolvem traumas de alta energia) ou em esportes em que h&#225; a intera&#231;&#227;o com artefatos em alta velocidade (por exemplo, beisebol), a preocupa&#231;&#227;o com o <italic>commotio cordis</italic> (arritmia maligna desencadeada por trauma direto no t&#243;rax anterior) deve estar presente.<xref ref-type="bibr" rid="B31">31</xref> At&#233; onde temos informa&#231;&#227;o, dados relacionados ao <italic>commotio cordis</italic> s&#227;o inexistente nas estat&#237;sticas brasileiras.</p>
        </sec>
        <sec>
          <title>Futuras dire&#231;&#245;es</title>
          <p>Com o exposto anteriormente, identificamos alguns pontos ainda desconhecidos que necessitam de investiga&#231;&#227;o priorit&#225;ria para defini&#231;&#245;es de estrat&#233;gias de rastreamento, preven&#231;&#227;o e regulamenta&#231;&#227;o nacional, os quais s&#227;o essenciais para o processo de ATS e podem ser alcan&#231;ados atrav&#233;s de um registro genuinamente brasileiro (<xref ref-type="fig" rid="f2">Figura 1</xref>).</p>
          <p>
            <fig id="f2">
              <label>Figura 1</label>
              <caption>
                <title>Proposi&#231;&#227;o de estat&#237;sticas a serem levantadas por um registro nacional de casos de MS no esporte competitivo em jovens atletas. MS: morte s&#250;bita.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-111-06-0856-80207-gf01-pt.jpg"/></fig>
          </p>
          <p>Salientamos o papel central que os &#243;rg&#227;os p&#250;blicos financiadores da pesquisa no Brasil t&#234;m para que um registro possa ser realizado. A abertura de editais de fomento espec&#237;ficos para tal nos parece aplic&#225;vel, preferencialmente de car&#225;ter multic&#234;ntrico e com o compartilhamento p&#250;blico dos dados. At&#233; o momento, na aus&#234;ncia de interesse por parte de pesquisadores independentes, o Estado ainda n&#227;o se posicionou e n&#227;o facilitou a implementa&#231;&#227;o de uma estrat&#233;gia vi&#225;vel para um registro nacional, o que consideramos ser um passo muito importante.</p>
        </sec>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>Lucas Helal recebe suporte financeiro para dedica&#231;&#227;o exclusiva &#224; pesquisa pela CAPES. Ricardo Stein &#233; Bolsista de Produtividade em Pesquisa do CNPq.</p>
        </fn>
      </fn-group>
      <fn-group>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>Este artigo &#233; parte de disserta&#231;&#227;o de Mestrado de Filipe Ferrari pelo Programa de p&#243;s-gradua&#231;&#227;o em Cardiologia e Ci&#234;ncias Cardiovasculares da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
