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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">JmyrbyT6y88Q9gWmsbQHh7D</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2016004500557</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20160178</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
          <subj-group>
            <subject>Heart Failure</subject>
          </subj-group>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Acute Heart Failure Registry: Risk Assessment Model in Decompensated Heart Failure</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Delgado</surname>
            <given-names>Anne</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rodrigues</surname>
            <given-names>Bruno</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nunes</surname>
            <given-names>Sara</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Baptista</surname>
            <given-names>Rui</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Marmelo</surname>
            <given-names>Bruno</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moreira</surname>
            <given-names>Davide</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gama</surname>
            <given-names>Pedro</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nunes</surname>
            <given-names>Lu&#237;s</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cabral</surname>
            <given-names>Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Centro Hospitalar Tondela Viseu</institution>
        <institution content-type="orgdiv1">Servi&#231;o de Cardiologia</institution>
        <addr-line>
          <named-content content-type="city">Viseu</named-content>
        </addr-line>
        <country country="PT">Portugal</country>
        <institution content-type="original">Servi&#231;o de Cardiologia, Centro Hospitalar Tondela Viseu; Viseu - Portugal</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Escola Superior de Gest&#227;o</institution>
        <institution content-type="orgdiv1">Instituto Polit&#233;cnico de Castelo Branco</institution>
        <addr-line>
          <named-content content-type="city">Viseu</named-content>
        </addr-line>
        <country country="PT">Portugal</country>
        <institution content-type="original">Instituto Polit&#233;cnico de Castelo Branco - Escola Superior de Gest&#227;o; Viseu - Portugal</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Universidade de Coimbra</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">IBILI Research Consortium</institution>
        <addr-line>
          <named-content content-type="city">Viseu</named-content>
        </addr-line>
        <country country="PT">Portugal</country>
        <institution content-type="original">CNC.IBILI Research Consortium - Faculdade de Medicina Universidade de Coimbra, Viseu - Portugal</institution>
        <institution content-type="normalized">Universidade de Coimbra</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing address: Anne Paula Delgado Bohlen</bold>, Servi&#231;o de Cardiologia - Centro Hospitalar Tondela Viseu. Edif&#237;cio EuroViso- LT E. n&#186; 403, 4&#186; Post, Santa Eug&#233;nia. CEP 3500-034, Santa Eug&#233;nia, Viseu - Portugal. E-mail: <email>anne_delgado@hotmail.com</email>, <email>annepdbohlen@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>Author contributions</p>
          <p>Conception and design of the research: Bohlen APD, Rodrigues B; Acquisition of data: Bohlen APD, Rodrigues B, Marmelo B, Moreira D, Gama P, Santos O; Analysis and interpretation of the data and Statistical analysis: Bohlen APD, Nunes S; Writing of the manuscript: Bohlen APD, Rodrigues B, Baptista R; Critical revision of the manuscript for intellectual content: Baptista R, Nunes L, Santos O, Cabral C.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potential Conflict of Interest</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>2016</year>
      </pub-date>
      <volume>107</volume>
      <issue>6</issue>
      <fpage>557</fpage>
      <lpage>567</lpage>
      <history>
        <date date-type="received">
          <day>05</day>
          <month>07</month>
          <year>2016</year>
        </date>
        <date date-type="rev-recd">
          <day>31</day>
          <month>08</month>
          <year>2016</year>
        </date>
        <date date-type="accepted">
          <day>31</day>
          <month>08</month>
          <year>2016</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Heart failure (HF) is a highly prevalent syndrome. Although the long-term prognostic factors have been identified in chronic HF, this information is scarcer with respect to patients with acute HF. despite available data in the literature on long-term prognostic factors in chronic HF, data on acute HF patients are more scarce.</p>
        </sec>
        <sec>
          <title>Objectives:</title>
          <p>To develop a predictor of unfavorable prognostic events in patients hospitalized for acute HF syndromes, and to characterize a group at higher risk regarding their clinical characteristics, treatment and outcomes.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>cohort study of 600 patients admitted for acute HF, defined according to the European Society of Cardiology criteria. Primary endpoint for score derivation was defined as all-cause mortality and / or rehospitalization for HF at 12 months. For score validation, the following endpoints were used: all-cause mortality and / or readmission for HF at 6, 12 and 24 months. The exclusion criteria were: high output HF; patients with acute myocardial infraction, acute myocarditis, infectious endocarditis, pulmonary infection, pulmonary artery hypertension and severe mitral stenosis.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>505 patients were included, and prognostic predicting factors at 12 months were identified. One or two points were assigned according to the odds ratio (OR) obtained (p &lt; 0.05). After the total score value was determined, a 4-point cut-off was determined for each ROC curve at 12 months. Two groups were formed according to the number of points, group A &lt; 4 points, and group B = 4 points. Group B was composed of older patients, with higher number of comorbidities and predictors of the combined endpoint at 6, 12 and 24 months, as linearly represented in the survival curves (Log rank).</p>
        </sec>
        <sec>
          <title>Conclusions:</title>
          <p>This risk score enabled the identification of a group with worse prognosis at 12 months.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Heart Failure/complications</kwd>
        <kwd>Prognosis</kwd>
        <kwd>Acute Coronary Syndrome</kwd>
        <kwd>Biomarkers</kwd>
        <kwd>Echocardiography,Doppler</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Heart failure (HF) is a syndrome with high prevalence (1-3% of the population, 5-10% among individuals aged 65-79 years, and 10-20% in older than 80 years), which has been increasing in the last decade due to population ageing and higher survival of subjects suffering from certain diseases, such as ischemic heart disease and arterial hypertension.<xref ref-type="bibr" rid="B1">1</xref>
			</p>
      <p>HF is characterized by a defective cardiac feeling and/or impairment of blood ejection according to metabolic needs, resulting in a classic constellation of signs and symptoms of pulmonary or systemic congestion.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref>
			</p>
      <p>HF is the first cause of early rehospitalizations (in the first 30 days) in elderly individuals. A high rate of readmission for acute HF is observed in the first month after hospital discharge.<xref ref-type="bibr" rid="B4">4</xref> Despite the significant increase in hospitalizations due to acute decompensated HF, models of risk stratification in patients hospitalized for acute HF have not been well established.<xref ref-type="bibr" rid="B5">5</xref> For this reason, clinical, analytical (including biomarkers) and echocardiographic tools for risk stratification may be useful in the medical decision making.<xref ref-type="bibr" rid="B6">6</xref> Among the biomarkers, natriuretic peptides, which are correlated with left ventricular telediastolic pressure (LVTP), usually increased in the HF, are strong prognostic predictors of rehospitalizations and/or death.<xref ref-type="bibr" rid="B7">7</xref>
			</p>
      <p>LVTP can also be predicted by echocardiography. The assessment of the relationship between mitral ring velocity and transmitral flow velocity curves by tissue Doppler echocardiography provides better estimates of LVTP as compared with other echocardiographic methods<xref ref-type="bibr" rid="B8">8</xref>.</p>
      <p>There are other classical biomarkers with prognostic value in HF. Natremia is inversely correlated with plasma renin activity and is a strong predictor of cardiovascular mortality.<xref ref-type="bibr" rid="B9">9</xref> Serum urea and creatinine levels are also predictors of a worse prognostic in HF<xref ref-type="bibr" rid="B10">10</xref>. Kidney injury in HF generally represents a combination of previous kidney injury, aggravation of renal perfusion, venous congestion and effect of therapy, namely angiotensin-converting-enzyme inhibitor (ACE inhibitor)/ angiotensin II receptor blockers (ARBs), diuretics and mineralocorticoid receptor antagonists (MRAs).<xref ref-type="bibr" rid="B10">10</xref>
			</p>
      <p>The benefits of the therapy with ACE inhibitors are noticed since the beginning of the therapy that continue in long-term, with greater reduction in the risk of death or rehospitalization for HF in patients with reduced left ventricular ejection fraction (LVEF).<xref ref-type="bibr" rid="B11">11</xref>
			</p>
      <p>Therefore, despite available data in the literature on long-term prognostic factors in chronic HF, data on (acute or chronic) decompensated HF patients are more scarce.<xref ref-type="bibr" rid="B12">12</xref>
			</p>
      <p>The aim of this analysis was to develop an AHFR (acute heart failure registry) score, predictor of unfavorable prognostic events in hospitalized patients with acute HF syndromes.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Study design</title>
        <p>We designed an observational, retrospective cohort study.</p>
      </sec>
      <sec>
        <title>Study population</title>
        <p>The total population consisted of 600 patients hospitalized for acute HF in a cardiology service of a non-tertiary hospital from 2009 to 2011. All patients signed the informed consent form, according to the protocol.</p>
        <p>Inclusion criterion was diagnosis of acute HF, defined according to the European Society of Cardiology criteria.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> Exclusion criteria were high-output HF, high suspicion for acute coronary syndrome as the etiology of HF at hospital admission (including patients requiring urgent reperfusion therapy), acute myocarditis, infectious endocarditis, pulmonary infection, pulmonary arterial hypertension, and severe mitral stenosis. Patients admitted and discharged in the emergency service were also excluded.</p>
      </sec>
      <sec>
        <title>Variables and definitions</title>
        <p>Variables of anthropometry, clinical presentations, comorbidities, precipitating factors, echocardiographic measurements, intra-hospital treatment and medications prescribed at discharge were included.</p>
        <p>Data collection and electrocardiography were conducted at patient's admission in the emergency service.</p>
        <p>Anemia and chronic kidney disease (CKD) were defined according to the National Kidney Foundation as hemoglobin &#8804;12g/dL for men and postmenopausal women, and estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) equation lower than 60 mL/min/1.73m<sup>2</sup> prior to hospital admission.</p>
        <p>Hypertensive crisis was defined as a relatively abrupt and symptomatic rise in systolic arterial pressure &#8805; 180 mmHg and/or diastolic arterial pressure &#8805; 110 mmHg.</p>
        <p>Non-hypertensive acute pulmonary edema (APE) was defined as a gradual or sudden onset of dyspnea, tachypnea, hypoxemia and/or radiologic changes compatible to pulmonary edema, and not precipitated by severe hypertension.</p>
        <p>Arrhythmia was defined as sustained ventricular tachycardia, atrial fibrillation (AF) or flutter with rapid response or any other supraventricular tachycardia. HF with preserved LVEF, evaluated approximately 72 hours after hospital admission for decompensated HF, was defined as the presence of HF signs and symptoms and LVEF higher than 50% and/or atrial dilation, mitral inflow E/A ratio &lt;1 or &gt;2, E/e' ratio &gt;15.<xref ref-type="bibr" rid="B14">14</xref> HF caused by valve heart disease included moderate or severe valve disease. Multifactorial HF refered to multiple anomalies; it is not possible to identify the main one.</p>
      </sec>
      <sec>
        <title>Endpoints</title>
        <p>Clinical follow-up of patients were performed up to 24 months (median time [interquartile range]. The primary endpoint for score derivation was defined as all-cause mortality and/or rehospitalization for HF at 12 months. For score validation, the following endpoints were used: (i) all-cause mortality and/or (ii) rehospitalization for HF at 6, 12 and 24 months of clinical follow-up.</p>
      </sec>
      <sec>
        <title>Echocardiographic study</title>
        <p>Transthoracic echocardiography was conducted during hospitalization (mean of 3.2 &#177; 2.8 days of hospital admission) with a GE Vivid 7&#174; echo machine. LVEF was determined by the biplane Simpson's method. The echocardiographic parameters 'estimated pulmonary artery systolic pressure' (PASP) and 'E/e' ratio' were also evaluated in the study.</p>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>Continuous variables were reported as mean and standard deviation, and percentage of patients in the intervals obtained with the cutoff points. Categorical variables were described as absolute and relative frequencies (%).</p>
        <p>The Student's t-test was used for continuous variables (that had previously passed the Kolmogorov-Smirnov normality test) and the chi-square test for comparisons between categorical variables.</p>
        <p>Logistic regression analysis and Cox regression were performed when appropriate (95% confidence interval). A significance level of p&lt;0.05 was adopted.</p>
        <p>Of the 600 patients included, 95 were lost to clinical follow-up. In the population of 505 patients, six independent, predicting variables of the event (death/rehospitalization for HF) were identified using the endpoint in 242 patients. Then, 337 patients were classified according to the risk score as Group A (lower risk) or Group B (higher risk) (<xref ref-type="fig" rid="f01">Figure 1</xref>).</p>
        <p>
          <fig id="f01">
            <label>Figure 1</label>
            <caption>
              <title>Diagram of study design with number of patients and number of variables.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-107-06-0557-60178-gf01.jpg"/></fig>
        </p>
        <p>It is important to assess this prognostic score regarding its discrimination and calibration. Discrimination was estimated by the area under the curve (AUC), and calibration was estimated by the Hosmer-Lemeshow test.</p>
        <p>All analyses were performed by the Statistical Package for The Social Sciences (SPSS) software, version 18.0.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Characterization of the study population</title>
        <p>Clinical characteristics of the patients from whom the score was obtained are shown in <xref ref-type="table" rid="t1">table 1</xref>. Clinical, analytical and echocardiographic markers that were independent predictors of the primary endpoint (death for any cause a/or rehospitalization at 12 months of clinical follow-up) were determined by Cox regression analysis. These markers corresponded to the variables included in the score (<xref ref-type="table" rid="t2">Table 2</xref>).</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>Characterization of the study population and predicting variables of mortality and/or rehospitalization at 12 months</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Characteristics</th>
                <th align="center">
								</th>
                <th align="center">Without endpoint at 12 M (n=263)</th>
                <th align="center">With endpoint at 12 M (n=242)</th>
                <th align="center">p value <xref ref-type="table-fn" rid="TFN2"><italic>*</italic></xref>
								</th>
              </tr>
            </thead>
            <tbody>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="left">Age &gt;75 years (%)</td>
                <td align="center">
								</td>
                <td align="center">55.5</td>
                <td align="center">70.2</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="left">Female (%)</td>
                <td align="center">
								</td>
                <td align="center">46.4</td>
                <td align="center">52.7</td>
                <td align="center">0.03</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="left">BMI (Kg/m<sup>2</sup>) mean &#177; SD</td>
                <td align="center">
								</td>
                <td align="center">28.2&#177;4.9</td>
                <td align="center">26.2&#177;5.2</td>
                <td align="center">0.01</td>
              </tr>
              <tr>
                <td align="left" rowspan="9" style="border-bottom-width:thin;border-bottom-style:solid">Risk/etiologic factors and associated comorbidities (%)</td>
                <td align="center">Diabetes mellitus</td>
                <td align="center">36.1</td>
                <td align="center">36.8</td>
                <td align="center">NS</td>
              </tr>
              <tr>
                <td align="left">Arterial hypertension</td>
                <td align="center">29.7</td>
                <td align="center">25.6</td>
                <td align="center">NS</td>
              </tr>
              <tr>
                <td align="center">Dyslipidemia</td>
                <td align="center">30.8</td>
                <td align="center">21.1</td>
                <td align="center">NS</td>
              </tr>
              <tr>
                <td align="center">Previous AMI</td>
                <td align="center">14.8</td>
                <td align="center">14.5</td>
                <td align="center">NS</td>
              </tr>
              <tr>
                <td align="center">Previous CTS</td>
                <td align="center">9.1</td>
                <td align="center">12</td>
                <td align="center">NS</td>
              </tr>
              <tr>
                <td align="center">Stroke</td>
                <td align="center">7.2</td>
                <td align="center">7.4</td>
                <td align="center">NS</td>
              </tr>
              <tr>
                <td align="center">Atrial fibrillation</td>
                <td align="center">48</td>
                <td align="center">53.5</td>
                <td align="center">0.01</td>
              </tr>
              <tr>
                <td align="center">CKD</td>
                <td align="center">21.0</td>
                <td align="center">42.3</td>
                <td align="center">0.02</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="center">Anemia</td>
                <td align="center">33.8</td>
                <td align="center">43.4</td>
                <td align="center">0.02</td>
              </tr>
              <tr>
                <td align="left" rowspan="4" style="border-bottom-width:thin;border-bottom-style:solid">Clinical parameters (%)</td>
                <td align="center">SAP &lt; 140 mmHg</td>
                <td align="center">52.5</td>
                <td align="center">61.2</td>
                <td align="center">0.04</td>
              </tr>
              <tr>
                <td align="center">Mean AP &lt; 95 mmHg</td>
                <td align="center">41.9</td>
                <td align="center">50.6</td>
                <td align="center">0.04</td>
              </tr>
              <tr>
                <td align="center">BMI &gt; 30Kg/m2</td>
                <td align="center">32.8</td>
                <td align="center">24.8</td>
                <td align="center">NS</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="center">HR &gt; 100 bpm</td>
                <td align="center">27</td>
                <td align="center">38.5</td>
                <td align="center">0.01</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="center">Radiologic parameters (%)</td>
                <td align="center">Pulmonary edema</td>
                <td align="center">45.1</td>
                <td align="center">54.7</td>
                <td align="center">0.03</td>
              </tr>
              <tr>
                <td align="left" rowspan="5" style="border-bottom-width:thin;border-bottom-style:solid">Laboratory parameters (%)</td>
                <td align="center">Hyponatremia (&lt; 135 mmoL/mL)</td>
                <td align="center">14.4</td>
                <td align="center">22.3</td>
                <td align="center">&lt; 0.01</td>
              </tr>
              <tr>
                <td align="center">BNP &#8805; 400 pg/mL at admission</td>
                <td align="center">48.3</td>
                <td align="center">61.4</td>
                <td align="center">&lt; 0.01</td>
              </tr>
              <tr>
                <td align="center">Urea &#8805; 60 mg/dL</td>
                <td align="center">39.2</td>
                <td align="center">52.5</td>
                <td align="center">&lt; 0.01</td>
              </tr>
              <tr>
                <td align="center">eGFR (MDRD) &lt; 60 mL/min/1.73m2</td>
                <td align="center">52.5</td>
                <td align="center">66.1</td>
                <td align="center">0.01</td>
              </tr>
              <tr>
                <td align="center" style="border-bottom-width:thin;border-bottom-style:solid">BNP at discharge &#8805; 400 pg/mL</td>
                <td align="center" style="border-bottom-width:thin;border-bottom-style:solid">27.3</td>
                <td align="center" style="border-bottom-width:thin;border-bottom-style:solid">46.0</td>
                <td align="center" style="border-bottom-width:thin;border-bottom-style:solid">&lt; 0.01</td>
              </tr>
              <tr>
                <td align="left" rowspan="3">Echocardiographic parameters (%)</td>
                <td align="center">E/e&#8217; ratio &gt; 15</td>
                <td align="center">38</td>
                <td align="center">56.6</td>
                <td align="center">&lt; 0.01</td>
              </tr>
              <tr>
                <td align="center">LVEF &lt; 35%</td>
                <td align="center">23.6</td>
                <td align="center">24.8</td>
                <td align="center">NS</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="center">PASP &gt; 50 mmHg</td>
                <td align="center">26.6</td>
                <td align="center">41.7</td>
                <td align="center">0.01</td>
              </tr>
              <tr>
                <td align="left" rowspan="6">Medication at discharge (%)</td>
                <td align="center">Loop diuretics</td>
                <td align="center">96.6</td>
                <td align="center">97.9</td>
                <td align="center">NS</td>
              </tr>
              <tr>
                <td align="center">Mineralocorticoid receptor antagonists</td>
                <td align="center">42.2</td>
                <td align="center">46.9</td>
                <td align="center">NS</td>
              </tr>
              <tr>
                <td align="center">ACE inhibitor/ARBs</td>
                <td align="center">86.7</td>
                <td align="center">76.3</td>
                <td align="center">&lt; 0.01</td>
              </tr>
              <tr>
                <td align="center">BB</td>
                <td align="center">44.5</td>
                <td align="center">37.3</td>
                <td align="center">NS</td>
              </tr>
              <tr>
                <td align="center">Statins</td>
                <td align="center">40.7</td>
                <td align="center">35.9</td>
                <td align="center">NS</td>
              </tr>
              <tr>
                <td align="center">BB or ACE inhibitors</td>
                <td align="center">69.6</td>
                <td align="center">66.5</td>
                <td align="center">NS</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>ARBs: angiotensin II receptor blockers; ACE: angiotensin-converting-enzyme; AMI: acute myocardial infarction; AP: arterial pressure; BB: beta-blockers; BMI: body mass index ; BNP: brain natriuretic peptide; CTS: cardiothoracic surgery; CKD: chronic kidney disease; eGFR: estimated glomerular filtration rate; HR: heart rate; LVEF: left ventricular ejection fraction; MDRD: modification of diet in renal disease; PASP: pulmonary artery systolic pressure; SAP: systolic arterial pressure;</p>
            </fn>
            <fn id="TFN2">
              <label>(*)</label>
              <p>between-group comparison.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t2">
          <label>Table 2</label>
          <caption>
            <title>Independent predictors of primary endpoint (mortality and/or rehospitalization for heart failure at 12 months of follow-up) by Cox multivariate regression analysis</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="40%"/>
              <col width="15%"/>
              <col width="15%"/>
              <col width="15%"/>
              <col width="15%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Variables</th>
                <th align="center">HR</th>
                <th align="center">Confidence Interval (95%)</th>
                <th align="center">p value</th>
                <th align="center">Score</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Age &#8805; 75 years</td>
                <td align="center">1.7</td>
                <td align="center">1.1-2.5</td>
                <td align="center">0.01</td>
                <td align="center">2</td>
              </tr>
              <tr>
                <td align="left">E/e&#8217; ratio &#8805; 15</td>
                <td align="center">1.6</td>
                <td align="center">1.1-2.3</td>
                <td align="center">0.009</td>
                <td align="center">2</td>
              </tr>
              <tr>
                <td align="left">BNP &#8805; 400 pg/mL</td>
                <td align="center">1.37</td>
                <td align="center">1.0-1.9</td>
                <td align="center">0.04</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Uremia &#8805; 60 mg/dL</td>
                <td align="center">1.15</td>
                <td align="center">1.0-1.5</td>
                <td align="center">0.04</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Natremia &lt; 135 mEq/L</td>
                <td align="center">1.37</td>
                <td align="center">1.0-1.8</td>
                <td align="center">0.03</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Without ACE inhibitor/ARBs<xref ref-type="table-fn" rid="TFN4">*</xref> at discharge</td>
                <td align="center">1.9</td>
                <td align="center">1.2-2.9</td>
                <td align="center">0.004</td>
                <td align="center">2</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN3">
              <p>BNP: brain-type natriuretic peptide; ACE: angiotensin-converting-enzyme; ARBs: angiotensin II receptor blockers;</p>
            </fn>
            <fn id="TFN4">
              <label>(*)</label>
              <p>in case of intolerance to ACE inhibitors.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>AHFR score: derivation</title>
        <p>One or two points (p.) were given according to the odds ratio (OR) obtained (p&lt;0.05); 1 point for OR&lt;1.5 and 2 points for OR&gt;1.5. The maximum total score was 9 points (<xref ref-type="table" rid="t2">Table 2</xref>). After calculation of total score, a 4-point cut-off was determined for each ROC curve at 12 months (<xref ref-type="fig" rid="f02">Figure 2</xref>). Two groups were formed based on the number of points, group A (n=195) &lt; 4 points versus group B (n=142) &#8805; 4 points.</p>
        <p>
          <fig id="f02">
            <label>Figure 2</label>
            <caption>
              <title>After the total score value was determined, a 4-point cut-off was determined for each ROC curve at 12 months.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-107-06-0557-60178-gf02.jpg"/></fig>
        </p>
      </sec>
      <sec>
        <title>AHFR score: validation</title>
        <p>Clinical, analytical, echocardiographic parameters as well as event rate (death for any cause and/or rehospitalization for HF) at 6, 12 and 24 months were compared between the two groups.</p>
        <p>Therefore, the area under the ROC curve for the endpoint (mortality and/or rehospitalization at 12 months) was 0.74, with an intermediate discrimination score. The score was predictor of the event (p&lt;0.001), with 65% accuracy.</p>
        <p>In <xref ref-type="table" rid="t3">table 3</xref>, comparisons of the two groups according to the AHFR score are found. Group B was composed of older patients, with lower body mass index and higher prevalence of kidney disease. Other risk factors for anemia observed in the study group included female gender and CKD.<xref ref-type="bibr" rid="B15">15</xref> In addition, group B had lower eGFR than group A (p&lt;0.001).</p>
        <table-wrap id="t3">
          <label>Table 3</label>
          <caption>
            <title>Clinical characterization by risk groups</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Characteristics</th>
                <th align="center">
								</th>
                <th align="center">Group A (n=195)</th>
                <th align="center">Group B (n=142)</th>
                <th align="center">p value <xref ref-type="table-fn" rid="TFN5">*</xref>
								</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left" rowspan="3" style="border-bottom-width:thin;border-bottom-style:solid">Age (mean &#177; SD)</td>
                <td align="center">Mean</td>
                <td align="center">75.2&#177;9.6</td>
                <td align="center">80.1&#177;9.6</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="center">Women</td>
                <td align="center">77.2&#177;8.2</td>
                <td align="center">81.6&#177;7.9</td>
                <td align="center">0.05</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="center">Men</td>
                <td align="center">73.3&#177;10.2</td>
                <td align="center">78.5&#177;11.0</td>
                <td align="center">0.002</td>
              </tr>
              <tr>
                <td align="left">Female (%)</td>
                <td align="center">
								</td>
                <td align="center">49.2 (n=195)</td>
                <td align="center">52.1(n=142)</td>
                <td align="center">0.6</td>
              </tr>
              <tr>
                <td align="left">Mean BMI (Kg/m<sup>2</sup>) &#177; SD</td>
                <td align="center">
								</td>
                <td align="center">28.2&#177;4.9</td>
                <td align="center">26.2&#177;5.2</td>
                <td align="center">0.01</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="left">Mean RICA score &#177; SD</td>
                <td align="center">
								</td>
                <td align="center">2.4&#177;1.4</td>
                <td align="center">5.8&#177;1.3</td>
                <td align="center">&lt;0.001</td>
              </tr>
              <tr>
                <td align="left" rowspan="10" style="border-bottom-width:thin;border-bottom-style:solid">Risk/etiologic factors and associated comorbidities (%)</td>
                <td align="center">DM</td>
                <td align="center">38.5</td>
                <td align="center">32.4</td>
                <td align="center">0.25</td>
              </tr>
              <tr>
                <td align="center">Arterial hypertension</td>
                <td align="center">72.8</td>
                <td align="center">57.0</td>
                <td align="center">0.003</td>
              </tr>
              <tr>
                <td align="center">Dyslipidemia</td>
                <td align="center">30.8</td>
                <td align="center">21.1</td>
                <td align="center">0.048</td>
              </tr>
              <tr>
                <td align="center">Known CHD</td>
                <td align="center">36.9</td>
                <td align="center">38.7</td>
                <td align="center">0.7</td>
              </tr>
              <tr>
                <td align="center">Previous AMI</td>
                <td align="center">13.4</td>
                <td align="center">17.4</td>
                <td align="center">0.6</td>
              </tr>
              <tr>
                <td align="center">Previous CTS</td>
                <td align="center">4.6</td>
                <td align="center">10.6</td>
                <td align="center">0.03</td>
              </tr>
              <tr>
                <td align="center">Stroke</td>
                <td align="center">9.7</td>
                <td align="center">7</td>
                <td align="center">0.38</td>
              </tr>
              <tr>
                <td align="center">AF</td>
                <td align="center">50</td>
                <td align="center">42.3</td>
                <td align="center">0.03</td>
              </tr>
              <tr>
                <td align="center">CKD</td>
                <td align="center">21.0</td>
                <td align="center">42.3</td>
                <td align="center">&lt;0.001</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="center">Anemia</td>
                <td align="center">37.4</td>
                <td align="center">57.7</td>
                <td align="center">&lt;0.001</td>
              </tr>
              <tr>
                <td align="left">Clinical presentation of HF (%)</td>
                <td align="center">Decompensated HF</td>
                <td align="center">67.7</td>
                <td align="center">72.5</td>
                <td align="center" rowspan="5">0.01</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">APE (nh)</td>
                <td align="center">13.3</td>
                <td align="center">11.3</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">APE (h)</td>
                <td align="center">16.9</td>
                <td align="center">7.7</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Cardiogenic shock</td>
                <td align="center">0.5</td>
                <td align="center">2.8</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="left">
								</td>
                <td align="center">Right HF</td>
                <td align="center">1.5</td>
                <td align="center">5.6</td>
              </tr>
              <tr>
                <td align="left">Precipitating factors (%)</td>
                <td align="center">Ischemia/ type 2 ACS</td>
                <td align="center">11.8</td>
                <td align="center">14.1</td>
                <td align="center" rowspan="4">0.03</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Cardiac arrhythmias</td>
                <td align="center">22.1</td>
                <td align="center">16.9</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Hypertensive crisis</td>
                <td align="center">15.9</td>
                <td align="center">7.0</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="left">
								</td>
                <td align="center">Multifactorial (renal dysfunction, anemia, infection, poor compliance to therapy, diet and others)</td>
                <td align="center">50.3</td>
                <td align="center">62.0</td>
              </tr>
              <tr>
                <td align="left" rowspan="2" style="border-bottom-width:thin;border-bottom-style:solid">HF subtypes (%)</td>
                <td align="center">HF with decreased LVEF</td>
                <td align="center">47.7</td>
                <td align="center">59.6</td>
                <td align="left">
								</td>
              </tr>
              <tr style="border-bottom-width:thin;border-bottom-style:solid">
                <td align="center">HF with preserved LFEV</td>
                <td align="center">52.3</td>
                <td align="center">40.4</td>
                <td align="left">
								</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Hypertensive heart diseases (including those associated with AF and DM)</td>
                <td align="center">33.3</td>
                <td align="center">28.9</td>
                <td align="center" rowspan="6">0.02</td>
              </tr>
              <tr>
                <td align="left">HF etiology (%)</td>
                <td align="center">Ischemic CM</td>
                <td align="center">25.6</td>
                <td align="center">40.1</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Non-ischemic DCM</td>
                <td align="center">21.0</td>
                <td align="center">15.5</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Valve disease</td>
                <td align="center">11.8</td>
                <td align="center">8.5</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Cor pulmonale</td>
                <td align="center">3.6</td>
                <td align="center">6.3</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Multifactorial</td>
                <td align="center">4.6</td>
                <td align="center">0.7</td>
              </tr>
              <tr style="border-top-width:thin;border-top-style:solid">
                <td align="left">Parameters at admission</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">AP (mean &#177; SD)</td>
                <td align="center">SAP (mmHg)</td>
                <td align="center">146.2&#177;30.5</td>
                <td align="center">130.9&#177;29.5</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">DAP (mmHg)</td>
                <td align="center">83.7&#177;19.9</td>
                <td align="center">75.4&#177;16.0</td>
                <td align="center">&lt;0.001</td>
              </tr>
              <tr>
                <td align="left">Laboratory</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">eGFR (mL/min) mean&#177; SD</td>
                <td align="center">51.0&#177;21.8</td>
                <td align="center">37.7&#177;17</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">eGFR MDRD &lt; 60 mL/min/1.73m<sup>2</sup> (%)</td>
                <td align="center">21</td>
                <td align="center">42.3</td>
                <td align="center">&lt;0.001</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Sodium &lt; 135 mmoL/L (%)</td>
                <td align="center">7.7</td>
                <td align="center">29.6</td>
                <td align="center">&lt; 0.01</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Potassium (mmol/L) mean &#177; SD</td>
                <td align="center">4.5&#177;0.6</td>
                <td align="center">4.7&#177;0.7</td>
                <td align="center">&lt; 0.01</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Hemoglobin (g/dL) mean&#177; SD</td>
                <td align="center">13.0&#177;2.0</td>
                <td align="center">12.2&#177;2.1</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">RDW &gt; 15 (%)</td>
                <td align="center">49.7</td>
                <td align="center">68.3</td>
                <td align="center">0.02</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">BNP &gt; 400 pg/mL at admission (%)</td>
                <td align="center">31.8</td>
                <td align="center">43.7</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">BNP &gt; 400 pg/mL at discharge (%)</td>
                <td align="center">10.3</td>
                <td align="center">37.3</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">PCR (mg/dl) mean &#177; SD</td>
                <td align="center">1.8&#177;2.4</td>
                <td align="center">2.5&#177;3.4</td>
                <td align="center">0.02</td>
              </tr>
              <tr style="border-top-width:thin;border-top-style:solid">
                <td align="left">Echocardiographic</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Mean LVEF (%)</td>
                <td align="center">50.1&#177;15.1</td>
                <td align="center">46.0&#177;16.8</td>
                <td align="center">0.02</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">LVEF &lt; 30% (%)</td>
                <td align="center">10.8</td>
                <td align="center">17.0</td>
                <td align="center">0.04</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">LVEF 30-44% (%)</td>
                <td align="center">28.7</td>
                <td align="center">35.5</td>
                <td align="center">0.04</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">LVEF &#8805; 50% (%)</td>
                <td align="center">52.3</td>
                <td align="center">40.4</td>
                <td align="center">0.04</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">PASP (mmHg) mean&#177; SD</td>
                <td align="center">42.2&#177;12.9</td>
                <td align="center">50.0&#177;14.7</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr style="border-top-width:thin;border-top-style:solid">
                <td align="left">Medication at discharge (%)</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">BB</td>
                <td align="center">46.2</td>
                <td align="center">33.1</td>
                <td align="center">0.02</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">ACE inhibitors</td>
                <td align="center">68.7</td>
                <td align="center">52.1</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">ARBs</td>
                <td align="center">24.1</td>
                <td align="center">12.7</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">BB+ ACE inhibitors/ARBs</td>
                <td align="center">44.1</td>
                <td align="center">23.9</td>
                <td align="center">0.04</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Furosemide</td>
                <td align="center">95.4</td>
                <td align="center">96.5</td>
                <td align="center">0.6</td>
              </tr>
              <tr>
                <td align="left">
								</td>
                <td align="center">Spironolactone</td>
                <td align="center">39</td>
                <td align="center">46.5</td>
                <td align="center">0.1</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN5">
              <p>ACE: angiotensin-converting-enzyme; ACS: acute coronary syndrome; AF: atrial fibrillation; AHFR: acute heart failure registry; AMI: acute myocardial infarction; APE (h): acute pulmonary edema (hypertensive); APE (nh): acute pulmonary edema (non-hypertensive); ARBs: angiotensin II receptor blockers; BB: beta-blockers; BMI: body mass index; CAD: coronary artery disease; CG: Cockcroft-Gault; CKD: chronic kidney disease; CM: cardiomyopathy; CTS: cardiothoracic surgery; DAP: diastolic arterial pressure; DCM: dilated cardiomyopathy; DM: diabetes mellitus; eGFR:- estimated glomerular filtration rate; LVEF: left ventricular ejection fraction; HF: heart failure; MDRD: modification of diet in renal disease ; PCR: protein chain reaction; PASP: pulmonary artery systolic pressure; RDW: red cell distribution width; SAP: systolic arterial pressure; SD: standard-deviation;</p>
            </fn>
            <fn id="TFN6">
              <label>(*)</label>
              <p>comparison between the risk groups (A e B).</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>With respect to electrocardiographic changes, AF rhythm was predominant in group A, whereas other non-sinus rhythm was predominant in group B (p&lt;0.01). No statistically significant differences in intraventricular conduction (QRS) duration were detected between the groups.</p>
        <p>The identification of the precipitating factor is crucial for patient's stabilization.<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref> In our study, the most frequent precipitating factor was multifactorial (including low compliance to diet and therapy) in both groups.</p>
        <p>The most frequent HF etiology was ischemic heart disease (40.1%).</p>
        <p>In group B, we found a high proportion of older patients non-adherent to the therapy and posology proposed.</p>
        <p>In group B, nearly 40% of patients had LVEF higher than 50%. Other echocardiographic parameters are described in <xref ref-type="table" rid="t3">table 3</xref>.</p>
        <p>Medication started during hospitalization was considered of higher relevance and prognostic impact. At hospital discharge, approximately 52% of patients in group B were receiving ACE inhibitors and 46% spironolactone, and 20% of them had LVEF lower than 30%. Medications received by the patients at discharge are described in <xref ref-type="table" rid="t3">table 3</xref>.</p>
        <p>Mean hospital stay duration was 8.6 &#177; 7 days, with a mean of 10 (&#177;7.7) days in group B.</p>
        <p>AHFR score as predictor of events during clinical follow-up</p>
        <p>Rehospitalization rates at 6, 12 and 24 months are shown in <xref ref-type="table" rid="t4">table 4</xref>.</p>
        <table-wrap id="t4">
          <label>Table 4</label>
          <caption>
            <title>Rate of rehospitalization for heart failure at 6, 12 and 24 months by risk groups</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Rehospitalization (%)</th>
                <th align="center">Group A</th>
                <th align="center">Group B</th>
                <th align="center">OR (IC 95%)</th>
                <th align="center">p value</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">6 months</td>
                <td align="center">21.5</td>
                <td align="center">30.5</td>
                <td align="center">1.6 (1.2-2.6)</td>
                <td align="center">0.04</td>
              </tr>
              <tr>
                <td align="left">12 months</td>
                <td align="center">34.7</td>
                <td align="center">44.4</td>
                <td align="center">1.6 (1.2- 2.5)</td>
                <td align="center">0.04</td>
              </tr>
              <tr>
                <td align="left">24 months</td>
                <td align="center">48.2</td>
                <td align="center">58.7</td>
                <td align="center">1.5 (0.9-2.4)</td>
                <td align="center">0.06</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>Nearly one-fourth of patients in group B were rehospitalized within 90 days after hospital discharge. Approximately 25% of patients in group A and 50% in group B reached the endpoint at 6 months after discharge (p&lt;0.001). However, in both groups, the rehospitalization rate for decompensated HF and/or all-cause mortality was higher at three months after discharge, as indicated in the Kaplan Meier curves (<xref ref-type="fig" rid="f03">Figures 3A</xref>, <xref ref-type="fig" rid="f03">B</xref> and <xref ref-type="fig" rid="f03">C</xref>).</p>
        <p>
          <fig id="f03">
            <label>Figure 3</label>
            <caption>
              <title>Kaplan Meier curves showing the rate of combined endpoint (mortality and/or rehospitalization) of group A (score &lt; 4) and group B (score &gt; 4) at 6 (A), 12 (B) and 24 months (C) of clinical follow-up.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-107-06-0557-60178-gf03.jpg"/></fig>
        </p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>In this retrospective study, a new risk score for medium-term events was constructed in patients hospitalized for acute HF syndrome. The inclusion of four variables previously identified in risk models and the identification of two new variables - E/e' ratio and lack of ACE inhibitor/ARBs (for those intolerant to ACE inhibitors) prescription at discharge - enabled the identification of a high-risk group, with score higher than 4 (group B). This group was mostly constituted of older patients, who exhibited higher number of comorbidities, higher hemodynamic instability at admission, higher left ventricular dysfunction and worse prognosis in short, medium and long term.</p>
      <p>The identification and clinical characterization of a higher risk group for events facilitates an earlier multidisciplinary approach, and promotes the correct identification of decompensating factors, higher therapy compliance, and reduced hospital stay, hospital morbimortality and readmission that consume most of the resources involved in this syndrome.<xref ref-type="bibr" rid="B5">5</xref>
			</p>
      <p>Four of the variables included in the score developed in this study are also present in many models. Nevertheless, our study is original in including an echocardiographic variable (E/e' ratio) determined during hospitalization and another variable determined on the day of discharge (lack of ACE inhibitor/ARBs prescription). As in previous models, this score enabled the identification of a higher risk, older group, with higher number of comorbidities, named cardiorenal syndrome.</p>
      <p>The risk models used in acute HF have several particularities. First, patients are assessed at admission or at the emergency service, which generally prioritizes the assessment of a very short- term risk (during hospitalization) or a medium-term risk (from 2 to 6 months after discharge), as the identification of high-risk patients contributes to a closer follow-up and more intensive therapy in this period when patients are more vulnerable.<xref ref-type="bibr" rid="B18">18</xref> For this reason, the variables of these models may be similar but are slightly different as compared with those of chronic HF scores, in emphasizing easy, rapidly accessible clinical, demographic and analytical factors.<xref ref-type="bibr" rid="B18">18</xref>
			</p>
      <p>The aim of this study was to evaluate medium-term risk (12 months) by including a variable different from the majority of the models - the lack of ACE inhibitor/ARBs (if intolerant to ACE inhibitor) prescription at discharge. Although "intra-hospital mortality" or "mortality at 90 days" endpoints seem to be more relevant in acute diseases, including acute HF, long-term follow-up cannot be neglected, and other variables such as evidence-based therapy that has a later impact on the prognosis should be included.</p>
      <p>Several prognostic models in the context of acute HF are available in the literature. These models can be classified into three groups: five models were conducted with hospitalized patients, one included hospitalized patients included in clinical trials, and two models were conducted in an emergency service. <xref ref-type="table" rid="t5">Table 5</xref> describes the summary of the prognostic models in acute HF.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref><sup>-</sup><xref ref-type="bibr" rid="B25">25</xref> Three markers included in the score created by us - age, natremia, and uremia - are common in most of the models. The prognosis of acute HF progressively worsens with age, for the effect of age <italic>per se</italic> and for its association with higher comorbidity and frailty.<xref ref-type="bibr" rid="B26">26</xref> Renal failure is common among patients with acute HF. Some studies have reported that high levels of urea triplicate the risk for intra-hospital mortality and post-discharge mortality.<xref ref-type="bibr" rid="B10">10</xref> With respect to hyponatremia, a multivariate analysis showed that a 3 mmoL/L decrease in case of natremia lower than 140mmoL/L increases the intra-hospital mortality by 19.5%.<xref ref-type="bibr" rid="B9">9</xref>
			</p>
      <table-wrap id="t5">
        <label>Table 5</label>
        <caption>
          <title>Prognostic models in acute heart failure <xref ref-type="table-fn" rid="TFN7">*</xref>
					</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="16%"/>
            <col width="16%"/>
            <col width="16%"/>
            <col width="16%"/>
            <col width="16%"/>
            <col width="16%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">Author</th>
              <th align="center">Year of publication</th>
              <th align="center">Deriving cut-off (n)</th>
              <th align="center">Validation cut-off (n)</th>
              <th align="center">Variables (n)</th>
              <th align="center">Result/AUC</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">ADHERE<xref ref-type="bibr" rid="B6">6</xref> Fonarrow</td>
              <td align="center">2005</td>
              <td align="center">International Multicentric (33,046)</td>
              <td align="center">Multicentric (32,229)</td>
              <td align="center">Age. Clinical Laboratory (4)</td>
              <td align="center">IHM/ 0.75</td>
            </tr>
            <tr>
              <td align="left">AHFI <xref ref-type="bibr" rid="B19">19</xref> Auble</td>
              <td align="center">2005 (derivation) 2008 (validation)</td>
              <td align="center">National Multicentric (33,533)</td>
              <td align="center">Randomized sample (8,384)</td>
              <td align="center">Demographic Clinical Laboratory Non-invasive diagnostic tests (21)</td>
              <td align="center">IHM/ 0.59</td>
            </tr>
            <tr>
              <td align="left">GWTG-HF <xref ref-type="bibr" rid="B21">21</xref>Peterson</td>
              <td align="center">2010</td>
              <td align="center">International Multicentric Community (27,850)</td>
              <td align="center">Multicentric Community (11,933)</td>
              <td align="center">Demographic Clinical Laboratory Comorbidities 7)</td>
              <td align="center">IHM / 0.75</td>
            </tr>
            <tr>
              <td align="left">EFFECT<xref ref-type="bibr" rid="B22">22</xref> Lee</td>
              <td align="center">2003</td>
              <td align="center">National Multicentric (2,624)</td>
              <td align="center">Multicentric Community (1,407)</td>
              <td align="center">Demographic Clinical Laboratory Comorbidities (10)</td>
              <td align="center">Mortality in 30 days /0.79 Mortality at one year /0.76</td>
            </tr>
            <tr>
              <td align="left">OPTIMIZE-HF<xref ref-type="bibr" rid="B20">20</xref> O&#8217;Connor</td>
              <td align="center">2008</td>
              <td align="center">International Multicentric Registry (4,402)</td>
              <td align="center">OPTIME CHF (949) y ESCAPE (433)</td>
              <td align="center">Demographic Clinical Laboratory Comorbidities (13)</td>
              <td align="center">Mortality in 60-90 days/0.72</td>
            </tr>
            <tr>
              <td align="left">OPTIMIZE-HF<xref ref-type="bibr" rid="B5">5</xref> Abraham</td>
              <td align="center">2008</td>
              <td align="center">International Multicentric Registry (37,548)</td>
              <td align="center">Internal Bootstrapping ADHERE trial (181,830)</td>
              <td align="center">Demographic Clinical Laboratory Systolic dysfunction (7)</td>
              <td align="center">IHM/ 0.74</td>
            </tr>
            <tr>
              <td align="left">OPTIME CHF<xref ref-type="bibr" rid="B23">23</xref> Felker</td>
              <td align="center">2004</td>
              <td align="center">International Multicentric (949</td>
              <td align="center">Internal Bootstrapping</td>
              <td align="center">Demographic Clinical Laboratory (5)</td>
              <td align="center">Mortality in 60 days/0.77</td>
            </tr>
            <tr>
              <td align="left">Otawa<xref ref-type="bibr" rid="B24">24</xref> Stiell</td>
              <td align="center">2013</td>
              <td align="center">National Multicentric Community (507)</td>
              <td align="center">Internal Bootstrapping</td>
              <td align="center">Clinical laboratory (10)</td>
              <td align="center">Mortality in 30 days or non-fatal event in 14 days /BNP 0.77. no BNP 0.75</td>
            </tr>
            <tr>
              <td align="left">EHRMG<xref ref-type="bibr" rid="B25">25</xref> Lee</td>
              <td align="center">2012</td>
              <td align="center">National Multicentric Community (7,433)</td>
              <td align="center">Multicentric Community (5,158)</td>
              <td align="center">Clinical Laboratory Comorbidities (10)</td>
              <td align="center">Mortality in 7 days/0.8</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN7">
            <p>AUC: area under the curve; ADHERE: Acute Decompensated Heart Failure National Registry; AHFI: Acute Heart Failure Index; EFFECT: Enhanced Feedback for Effective Cardiac Treatment; EHMRG: Emergency Heart Failure Mortality Risk; GWTG-HF: Get With the Guidelines-Heart Failure; OPTIMIZE-HF: Organized Program to initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure; OPTIME-CHF: Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure; Ottawa: Ottawa Heart Failure Risk Model;</p>
          </fn>
          <fn id="TFN8">
            <label>(*)</label>
            <p>Adapted from Ferrero P. et al. Int J Cardiol. 2015;188:1-920<xref ref-type="bibr" rid="B18">18</xref>.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Despite higher availability and proved prognostic utility of natriuretic peptides, these compounds have not been included in most of the risk prediction models. Some studies suggest that an increment by 30% in normal NT-proBNP levels at admission increases by six times the risk of rehospitalization.<xref ref-type="bibr" rid="B27">27</xref>
			</p>
      <p>The assessment of the relationship of mitral ring velocity with transmitral flow velocity curves (E/e' ratio) by tissue Doppler was found to be an independent predictor of yearly mortality in patients hospitalized for acute HF.<xref ref-type="bibr" rid="B28">28</xref>
			</p>
      <p>Although the benefits of an early start of ACE inhibitors in acute HF have not been demonstrated in the literature, their prescription is mandatory within the first 48h-72h after admission, with proven benefits in reducing mortality and rehospitaization rate, according to the European Society of Cardiology recommendations.<xref ref-type="bibr" rid="B3">3</xref>
			</p>
      <p>Despite numerous studies showing that the lack of the prescription of beta-blockers at discharge is a mortality predicting factor, this was not observed in this study, probably due to a selection bias.</p>
      <p>The estimated risk at hospital admission may help to decide whether or not a patient is candidate for intensive therapy. However, several studies have shown that risk scores estimated on the day of discharge (including biomarkers and therapy prescribed at discharge) have better prognostic value as compared with those determined at admission.<xref ref-type="bibr" rid="B29">29</xref> Risk predicting tools are crucial to determine the prognosis in HF. Although these risk models can precisely determine short-term prognosis of acute HF, they should be extensively tested in elderly patients or those with multiple comorbidities.<xref ref-type="bibr" rid="B29">29</xref> Besides, prospective, randomized studies are needed to establish the impact of long term risk stratification on acute HF patients.<xref ref-type="bibr" rid="B29">29</xref>
			</p>
      <sec>
        <title>Limitations</title>
        <p>Some limitations inherent in the construction of this score should be considered in the interpretation of the results. The fact that this is a retrospective study opens up the possibility of selection bias. An external validation of the model is needed, preferentially in another center. The diagnosis of acute HF was based only on the European Society of Cardiology criteria and the date of onset of symptoms was not determined. For this reason, it is not possible to differentiate <italic>de novo</italic> acute HF from acutely worsened chronic HF. In addition, analysis of treatment and prognosis should be adjusted because of the heterogeneity of the sample. Another limitation refers to the fact that we did not include patients discharged home from the emergency department. Also, there was a large number of missing variables when the completion of data was optional, which affected the results. The echocardiography was performed some days post-admission, rather than on the day of admission, which may influence the measurements used in the score construction.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusions</title>
      <p>In this study, we constructed a new risk score of medium-term events in patients hospitalized for acute HF syndrome. The inclusion of four variables previously identified in risk models, in addition to the identification of two additional variables: E/e' ratio and lack of ACE inhibitor/ARBs prescription on the day of discharge enabled the identification of group at high risk for all-cause mortality at 12 months after discharge. This group (group B), with score higher than 4, was mostly constituted of older patients, who exhibited higher number of comorbidities, higher hemodynamic instability at admission, higher left ventricular dysfunction and worse prognosis in short, medium and long term. This group may benefit from a closer monitoring and early start of evidence-based therapy.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>Sources of Funding</p>
        <p>There were no external funding sources for this study.</p>
      </fn>
    </fn-group>
    <fn-group>
      <fn fn-type="other">
        <p>Study Association</p>
        <p>This study is not associated with any thesis or dissertation work.</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
          <subj-group>
            <subject>Insufici&#234;ncia Card&#237;aca</subject>
          </subj-group>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Registro de Insufici&#234;ncia Card&#237;aca Aguda: Modelo de Avalia&#231;&#227;o de Risco na Insufici&#234;ncia Card&#237;aca Descompensada</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Delgado</surname>
            <given-names>Anne</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rodrigues</surname>
            <given-names>Bruno</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nunes</surname>
            <given-names>Sara</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Baptista</surname>
            <given-names>Rui</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Marmelo</surname>
            <given-names>Bruno</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moreira</surname>
            <given-names>Davide</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gama</surname>
            <given-names>Pedro</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nunes</surname>
            <given-names>Lu&#237;s</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cabral</surname>
            <given-names>Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
        </contrib>
      </contrib-group>
      <aff id="aff4">
        <label>1</label>
        <institution content-type="original">Servi&#231;o de Cardiologia, Centro Hospitalar Tondela Viseu; Viseu - Portugal</institution>
      </aff>
      <aff id="aff5">
        <label>2</label>
        <institution content-type="original">Instituto Polit&#233;cnico de Castelo Branco - Escola Superior de Gest&#227;o; Viseu - Portugal</institution>
      </aff>
      <aff id="aff6">
        <label>3</label>
        <institution content-type="original">CNC.IBILI Research Consortium - Faculdade de Medicina Universidade de Coimbra, Viseu - Portugal</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Anne Paula Delgado Bohlen</bold>, Servi&#231;o de Cardiologia - Centro Hospitalar Tondela Viseu. Edif&#237;cio EuroViso- LT E. n&#186; 403, 4&#186; Post, Santa Eug&#233;nia. CEP 3500-034, Santa Eug&#233;nia, Viseu - Portugal. E-mail: <email>anne_delgado@hotmail.com</email>, <email>annepdbohlen@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>Contribui&#231;&#227;o dos autores</p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Bohlen APD, Rodrigues B; Obten&#231;&#227;o de dados: Bohlen APD, Rodrigues B, Marmelo B, Moreira D, Gama P, Santos O; An&#225;lise e interpreta&#231;&#227;o dos dados e An&#225;lise estat&#237;stica: Bohlen APD, Nunes S; Reda&#231;&#227;o do manuscrito: Bohlen APD, Rodrigues B, Baptista R; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Baptista R, Nunes L, Santos O, Cabral C.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potencial conflito de interesse</p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>A insufici&#234;ncia card&#237;aca (IC) &#233; uma s&#237;ndrome de elevada preval&#234;ncia. Apesar de existir na literatura informa&#231;&#227;o relativa aos fatores progn&#243;sticos a longo prazo na IC cr&#244;nica, esta &#233; mais escassa no que diz respeito aos pacientes com IC aguda.</p>
        </sec>
        <sec>
          <title>Objetivos:</title>
          <p>Desenvolver um score preditor de eventos progn&#243;sticos desfavor&#225;veis em doentes admitidos com s&#237;ndromes de IC aguda e caracterizar um grupo de maior risco quanto &#224;s suas caracter&#237;sticas cl&#237;nicas, terap&#234;utica e resultados.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Estudo de coorte de 600 doentes internados com IC aguda, definida de acordo com os crit&#233;rios da Sociedade Europeia de Cardiologia. O endpoint prim&#225;rio para a deriva&#231;&#227;o do score foi definido como mortalidade de qualquer causa e/ou reinterna&#231;&#227;o por IC aos 12 meses. Para a valida&#231;&#227;o do score, foram utilizados como <italic>endpoints</italic>: mortalidade de qualquer causa e/ou reinterna&#231;&#227;o por IC aos 6, 12 e 24 meses. Os crit&#233;rios de exclus&#227;o foram: IC de alto d&#233;bito, pacientes com infarto agudo do mioc&#225;rdio, miocardite aguda, endocardite infeciosa, infe&#231;&#227;o pulmonar, hipertens&#227;o arterial pulmonar e estenose mitral grave.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Foram inclu&#237;dos 505 doentes e identificados preditores progn&#243;sticos aos 12 meses. Atribu&#237;ram-se 1 ou 2 pontos (p.) de acordo com os <italic>odds ratio</italic> (OR) obtidos (p &lt; 0,05). Ap&#243;s a determina&#231;&#227;o do valor de score total, foi estabelecido um cut-off de 4 pontos por curva ROC. Constitu&#237;ram-se 2 grupos de acordo com a pontua&#231;&#227;o, grupo A &lt; 4 p. versus grupo B = 4 p. O grupo B era constitu&#237;do por idosos, com maior n&#250;mero de comorbidades e preditor de <italic>endpoint</italic> combinado aos 6, 12 e 24 meses traduzido linearmente nas curvas de sobrevida (Log rank).</p>
        </sec>
        <sec>
          <title>Conclus&#245;es:</title>
          <p>Este score de risco permitiu identificar um grupo com pior progn&#243;stico aos 12 meses.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Insufici&#234;ncia Card&#237;aca/complica&#231;&#245;es</kwd>
        <kwd>Progn&#243;stico</kwd>
        <kwd>S&#237;ndrome Coronariana Aguda</kwd>
        <kwd>Biomarcadores</kwd>
        <kwd>Ecocardiografia Doppler</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A insufici&#234;ncia card&#237;aca (IC) &#233; uma s&#237;ndrome de elevada preval&#234;ncia (1-3% da popula&#231;&#227;o geral, 5-10% na faixa dos 65-79 anos e 10-20% em maiores de 80 anos), tendo aumentado nas &#250;ltimas d&#233;cadas devido ao envelhecimento populacional e &#224; maior sobrevida de indiv&#237;duos acometidos por certas doen&#231;as, como a cardiopatia isqu&#234;mica e a hipertens&#227;o arterial.<xref ref-type="bibr" rid="B1">1</xref>
				</p>
        <p>&#201; caracterizada por uma deficiente capacidade de enchimento do cora&#231;&#227;o e/ou deficiente capacidade em ejetar o sangue de acordo com as necessidades metab&#243;licas do organismo, resultando numa constela&#231;&#227;o cl&#225;ssica de sinais e sintomas de congest&#227;o pulmonar ou sist&#233;mica.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref>
				</p>
        <p>A IC &#233; a primeira causa de reinterna&#231;&#245;es precoces (nos primeiros 30 dias) em idosos. Verifica-se um elevado n&#250;mero de readmiss&#245;es por IC aguda no primeiro m&#234;s ap&#243;s a alta hospitalar.<xref ref-type="bibr" rid="B4">4</xref> Apesar do aumento significativo do n&#250;mero de internamentos por descompensa&#231;&#227;o aguda de IC, os modelos para a estratifica&#231;&#227;o de risco dos doentes internados por IC aguda n&#227;o se encontram bem estabelecidos.<xref ref-type="bibr" rid="B5">5</xref> Deste modo, ferramentas cl&#237;nicas, anal&#237;ticas (incluindo biomarcadores) e ecocardiogr&#225;ficas de estratifica&#231;&#227;o de risco podem ser &#250;teis para orientar a decis&#227;o m&#233;dica.<xref ref-type="bibr" rid="B6">6</xref> Entre os biomarcadores, pept&#237;deos natriur&#233;ticos, que se correlacionam com a press&#227;o telediast&#243;lica do ventr&#237;culo esquerdo (PTDVE), habitualmente elevada na IC, s&#227;o potentes preditores progn&#243;sticos de reinterna&#231;&#227;o e/ou morte.<xref ref-type="bibr" rid="B7">7</xref>
				</p>
        <p>Outra forma de se estimar a PTDVE &#233; por ecocardiografia. A avalia&#231;&#227;o da rela&#231;&#227;o entre a velocidade do anel mitral e das curvas de velocidade do fluxo transmitral (E/e' ratio) por <italic>doppler</italic> tecidual fornece melhores estimativas da PTDVE do que outros m&#233;todos ecocardiogr&#225;ficos.<xref ref-type="bibr" rid="B8">8</xref>
				</p>
        <p>Outros biomarcadores cl&#225;ssicos tamb&#233;m t&#234;m valor progn&#243;stico no contexto da IC. A natremia tem uma correla&#231;&#227;o inversa com atividade da renina plasm&#225;tica e &#233; um forte preditor de mortalidade cardiovascular.<xref ref-type="bibr" rid="B9">9</xref> A ureia e creatinina s&#233;ricas s&#227;o igualmente preditores de pior progn&#243;stico na IC.<xref ref-type="bibr" rid="B10">10</xref> A les&#227;o renal na IC geralmente representa uma combina&#231;&#227;o de les&#227;o renal pr&#233;via, agravamento da perfus&#227;o renal, congest&#227;o venosa e efeito da terap&#234;utica, nomeadamente inibidores da enzima de convers&#227;o da angiotensina-aldosterona (IECA)/ antagonistas dos receptores da angiotensina II (ARA II), diur&#233;ticos e antagonistas dos receptores dos mineralocortic&#243;ides (ARM).<xref ref-type="bibr" rid="B10">10</xref>
				</p>
        <p>Os benef&#237;cios da terap&#234;utica com IECAs s&#227;o observados logo ap&#243;s o in&#237;cio do tratamento e persistem a longo prazo, existindo uma maior redu&#231;&#227;o no risco de morte ou readmiss&#227;o por IC em doentes com fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda (FEVE) diminu&#237;da.<xref ref-type="bibr" rid="B11">11</xref>
				</p>
        <p>Assim, apesar de existir na literatura informa&#231;&#227;o relativa aos fatores progn&#243;sticos a longo prazo na IC cr&#244;nica, esta &#233; mais escassa no que diz respeito aos doentes com IC descompensada (aguda ou cr&#244;nica).<xref ref-type="bibr" rid="B12">12</xref>
				</p>
        <p>O objetivo desta an&#225;lise foi desenvolver um <italic>score</italic>- RICA <italic>score</italic> (Registo de Insufici&#234;ncia Card&#237;aca Aguda) preditor de eventos progn&#243;sticos desfavor&#225;veis em doentes admitidos com s&#237;ndromes de IC aguda.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <sec>
          <title>Desenho do estudo</title>
          <p>Desenhamos um estudo, observacional, de coorte retrospectivo.</p>
        </sec>
        <sec>
          <title>Popula&#231;&#227;o do estudo</title>
          <p>A popula&#231;&#227;o total foi de 600 doentes internados por IC aguda num servi&#231;o de cardiologia de um hospital n&#227;o terci&#225;rio de 2009 a 2011. Todos os doentes assinaram o termo de consentimento livre e esclarecido, segundo o protocolo.</p>
          <p>O crit&#233;rio de inclus&#227;o foi diagn&#243;stico IC aguda, definida de acordo com os crit&#233;rios da Sociedade Europeia de Cardiologia.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> Os crit&#233;rios de exclus&#227;o foram IC de alto d&#233;bito, pacientes com suspeita elevada de s&#237;ndrome coron&#225;ria aguda como etiologia da IC &#224; admiss&#227;o (inclu&#237;do doentes com necessidade de terap&#234;utica de reperfus&#227;o urgente), miocardite aguda, endocardite infeciosa, infe&#231;&#227;o pulmonar, hipertens&#227;o arterial pulmonar e estenose mitral grave. Os doentes admitidos no servi&#231;o de urg&#234;ncia (SU), e que tiveram alta a partir do SU para o domic&#237;lio foram igualmente exclu&#237;dos.</p>
        </sec>
        <sec>
          <title>Vari&#225;veis e defini&#231;&#245;es</title>
          <p>As vari&#225;veis inclu&#237;das corresponderam a dados antropom&#233;tricos, tipos de apresenta&#231;&#227;o cl&#237;nica, comorbidades, fatores precipitantes, medidas ecocardiogr&#225;ficas, tratamento intra-hospitalar e medica&#231;&#227;o prescrita &#224; data de alta.</p>
          <p>A colheita de dados e o eletrocardiograma foram efetuados &#224; admiss&#227;o no SU.</p>
          <p>A anemia e a doen&#231;a renal cr&#244;nica (DRC) foram definidas segundo a <italic>National Kidney Foundation</italic> como hemoglobina &#8804; 12 g/dL no homem e na mulher p&#243;s-menop&#225;usica, e taxa de filtra&#231;&#227;o glomerular estimada (TFGe) pela f&#243;rmula <italic>Modification of Diet in Renal Disease</italic> (<italic>MDRD</italic>) inferior a 60 mL/min/1.73m<sup>2</sup> pr&#233;via &#224; interna&#231;&#227;o.</p>
          <p>A crise hipertensiva foi definida como eleva&#231;&#227;o, relativamente abrupta e sintom&#225;tica, da press&#227;o arterial sist&#243;lica &#8805; 180 mmHg e /ou press&#227;o arterial diast&#243;lica &#8805; 110 mmHg.</p>
          <p>O edema agudo do pulm&#227;o (EAP) n&#227;o hipertensivo foi definido como in&#237;cio gradual ou s&#250;bito de dispneia, taquipneia, hipoxemia e/ou altera&#231;&#245;es radiol&#243;gicas compat&#237;veis com edema pulmonar, e n&#227;o precipitado por hipertens&#227;o grave.</p>
          <p>A arritmia foi definida por taquicardia ventricular sustentada, fibrila&#231;&#227;o atrial (FA) ou <italic>flutter</italic> atrial com resposta ventricular r&#225;pida ou qualquer outra taquicardia supraventricular. A IC com FEVE preservada, avaliada aproximadamente 72 horas ap&#243;s a admiss&#227;o por IC descompensada, foi definida como presen&#231;a de sinais e sintomas de IC e FEVE superior a 50% e/ou presen&#231;a de dilata&#231;&#227;o atrial, raz&#227;o E/A de influxo mitral &lt;1 ou &gt;2 , raz&#227;o E/e' &gt;15.<xref ref-type="bibr" rid="B14">14</xref> A IC devido &#224; doen&#231;a card&#237;aca valvular incluiu a doen&#231;a valvular moderada ou grave. A IC multifatorial referiu-se &#224; exist&#234;ncia de v&#225;rias anomalias, n&#227;o sendo poss&#237;vel identificar a respons&#225;vel prim&#225;ria.</p>
        </sec>
        <sec>
          <title>Endpoints</title>
          <p>Foi efetuado um seguimento cl&#237;nico at&#233; aos 24 meses (tempo mediano [intervalo inter-quartil]). O <italic>endpoint</italic> prim&#225;rio para a deriva&#231;&#227;o do <italic>score</italic> foi definido como mortalidade de qualquer causa e/ou reinterna&#231;&#227;o por IC aos 12 meses. Para a valida&#231;&#227;o do score, foram utilizados os seguintes <italic>endpoints</italic>: (i) mortalidade de qualquer causa e/ou (ii) reinterna&#231;&#227;o por IC aos 6, 12 e 24 meses de seguimento cl&#237;nico.</p>
        </sec>
        <sec>
          <title>Estudo ecocardiogr&#225;fico</title>
          <p>A ecocardiografia transtor&#225;cica foi efetuada em regime de interna&#231;&#227;o (em m&#233;dia, 3,2 &#177; 2,8 dias ap&#243;s admiss&#227;o) com um ecocardi&#243;grafo GE Vivid 7&#174;. A FEVE foi determinada pelo m&#233;todo Simpson biplanar. Outros par&#226;metros ecocardiogr&#225;ficos foram press&#227;o sist&#243;lica na art&#233;ria pulmonar (PSAP) estimada e a raz&#227;o E/e'.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>As vari&#225;veis cont&#237;nuas foram caracterizadas por m&#233;dios e desvio-padr&#227;o, e porcentagens de doentes contidos nos intervalos obtidos a partir dos pontos de corte. As vari&#225;veis categ&#243;ricas foram descritas em frequ&#234;ncias absolutas e relativas (%).</p>
          <p>Utilizou-se o teste <italic>t</italic> de Student para as vari&#225;veis cont&#237;nuas (tendo sido previamente assegurada a normalidade dos dados pelo teste Kolmogorov-Smirnov) para amostras independentes e o teste &#967;-quadrado para compara&#231;&#245;es entre vari&#225;veis categ&#243;ricas.</p>
          <p>Foram conduzidas an&#225;lises de regress&#227;o log&#237;stica e regress&#227;o de Cox quando apropriadas (com intervalo de confian&#231;a a 95%). Utilizou-se um n&#237;vel de signific&#226;ncia de p &lt; 0,05.</p>
          <p>Dos 600 pacientes que entraram na an&#225;lise, 95 doentes perderam seguimento cl&#237;nico. Na popula&#231;&#227;o de 505 pacientes, seis vari&#225;veis de predi&#231;&#227;o do evento (morte/reinterna&#231;&#227;o por IC) independentes foram identificadas em 242 pacientes utilizando-se o <italic>endpoint</italic>, o que permitiu a sele&#231;&#227;o de 337 doentes, classificados, segundo o score de risco, em Grupo A (menor risco) ou Grupo B (maior risco) (<xref ref-type="fig" rid="f04">Figura 1</xref>).</p>
          <p>
            <fig id="f04">
              <label>Figura 1</label>
              <caption>
                <title>Diagrama do desenho do estudo com n&#250;mero de pacientes e n&#250;mero de vari&#225;veis.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-107-06-0557-60178-gf01-pt.jpg"/></fig>
          </p>
          <p>&#201; importante avaliar a representa&#231;&#227;o deste score progn&#243;stico mediante a sua discrimina&#231;&#227;o e calibra&#231;&#227;o. A discrimina&#231;&#227;o foi estimada pela &#225;rea sob a curva (AUC- a<italic>rea under the curve</italic>) e a calibra&#231;&#227;o foi estimada pelo teste de <italic>Hosmer-Lemeshow</italic>.</p>
          <p>Todas as an&#225;lises foram realizadas com o <italic>software</italic>
						<italic>Statistical Package for The Social</italic>
						<italic>Sciences</italic> (SPSS), vers&#227;o 18.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <sec>
          <title>Caracteriza&#231;&#227;o da popula&#231;&#227;o de estudo</title>
          <p>As caracter&#237;sticas cl&#237;nicas da popula&#231;&#227;o de doentes da qual derivou o <italic>score</italic> s&#227;o apresentadas na <xref ref-type="table" rid="t6">tabela 1</xref>. Os marcadores cl&#237;nicos, anal&#237;ticos e ecocardiogr&#225;ficos que foram preditores independentes do <italic>endpoint</italic> prim&#225;rio (morte por qualquer causa e/ou reinterna&#231;&#227;o aos 12 meses de seguimento cl&#237;nico) foram determinados pela an&#225;lise de regress&#227;o de Cox. Estes marcadores constitu&#237;ram as vari&#225;veis inclu&#237;das no <italic>score</italic> (<xref ref-type="table" rid="t2">Tabela 2</xref>).</p>
          <table-wrap id="t6">
            <label>Tabela 1</label>
            <caption>
              <title>Caracteriza&#231;&#227;o da popula&#231;&#227;o de estudo e var&#225;veis preditores de mortalidade e/ou reinternamento aos 12 meses</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Caracter&#237;sticas</th>
                  <th align="center">
									</th>
                  <th align="center">Sem <italic>endpoint</italic> aos 12 M (n=263)</th>
                  <th align="center">Com <italic>endpoint</italic> aos 12 M (n=242)</th>
                  <th align="center">Valor de p<xref ref-type="table-fn" rid="TFN10"><italic>*</italic></xref>
									</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Idade &gt;75 anos (%)</td>
                  <td align="center">
									</td>
                  <td align="center">55,5</td>
                  <td align="center">70,2</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left">G&#234;nero feminino (%)</td>
                  <td align="center">
									</td>
                  <td align="center">46,4</td>
                  <td align="center">52,7</td>
                  <td align="center">0,03</td>
                </tr>
                <tr>
                  <td align="left">IMC (Kg/m<sup>2</sup>) m&#233;dia&#177; DP</td>
                  <td align="center">
									</td>
                  <td align="center">28,2&#177;4,9</td>
                  <td align="center">26,2&#177;5,2</td>
                  <td align="center">0,01</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left" rowspan="9">Fatores de risco/etiol&#243;gicos e Comorbidades associadas (%)</td>
                  <td align="center">DM</td>
                  <td align="center">36,1</td>
                  <td align="center">36,8</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">HTA</td>
                  <td align="center">29,7</td>
                  <td align="center">25,6</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">DL</td>
                  <td align="center">30,8</td>
                  <td align="center">21,1</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">IAM pr&#233;vio</td>
                  <td align="center">14,8</td>
                  <td align="center">14,5</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">CCT pr&#233;via</td>
                  <td align="center">9,1</td>
                  <td align="center">12</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">AVC</td>
                  <td align="center">7,2</td>
                  <td align="center">7,4</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">FA</td>
                  <td align="center">48</td>
                  <td align="center">53,5</td>
                  <td align="center">0,01</td>
                </tr>
                <tr>
                  <td align="center">DRC</td>
                  <td align="center">21,0</td>
                  <td align="center">42,3</td>
                  <td align="center">0,02</td>
                </tr>
                <tr>
                  <td align="center">Anemia</td>
                  <td align="center">33,8</td>
                  <td align="center">43,4</td>
                  <td align="center">0,02</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left" rowspan="4">Par&#226;metros cl&#237;nicos (%)</td>
                  <td align="center">PAS&lt; 140 mmHg</td>
                  <td align="center">52,5</td>
                  <td align="center">61,2</td>
                  <td align="center">0,04</td>
                </tr>
                <tr>
                  <td align="center">PA m&#233;dia &lt; 95 mmHg</td>
                  <td align="center">41,9</td>
                  <td align="center">50,6</td>
                  <td align="center">0,04</td>
                </tr>
                <tr>
                  <td align="center">IMC &gt; 30 Kg/m<sup>2</sup></td>
                  <td align="center">32,8</td>
                  <td align="center">24,8</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">FC &gt; 100 bpm</td>
                  <td align="center">27</td>
                  <td align="center">38,5</td>
                  <td align="center">0,01</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left">Par&#226;metros radiol&#243;gicos (%)</td>
                  <td align="center">Edema pulmonar</td>
                  <td align="center">45,1</td>
                  <td align="center">54,7</td>
                  <td align="center">0,03</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left" rowspan="5">Par&#226;metros laboratoriais (%)</td>
                  <td align="center">Hiponatremia (&lt; 135 mmoL/mL)</td>
                  <td align="center">14,4</td>
                  <td align="center">22,3</td>
                  <td align="center">&lt; 0,01</td>
                </tr>
                <tr>
                  <td align="center">BNP &#8805; 400 pg/mL &#224; admiss&#227;o</td>
                  <td align="center">48,3</td>
                  <td align="center">61,4</td>
                  <td align="center">&lt; 0,01</td>
                </tr>
                <tr>
                  <td align="center">Ureia &#8805; 60 mg/dL</td>
                  <td align="center">39,2</td>
                  <td align="center">52,5</td>
                  <td align="center">&lt; 0,01</td>
                </tr>
                <tr>
                  <td align="center">TFGe (MDRD) &lt; 60 mL/min/1.73m2</td>
                  <td align="center">52,5</td>
                  <td align="center">66,1</td>
                  <td align="center">0,01</td>
                </tr>
                <tr>
                  <td align="center">BNP &#224; alta &#8805; 400 pg/mL</td>
                  <td align="center">27,3</td>
                  <td align="center">46,0</td>
                  <td align="center">&lt; 0,01</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left" rowspan="3">Par&#226;metros ecocardiogr&#225;ficas (%)</td>
                  <td align="center">Raz&#227;o E/e&#8217;&gt; 15</td>
                  <td align="center">38</td>
                  <td align="center">56,6</td>
                  <td align="center">&lt; 0,01</td>
                </tr>
                <tr>
                  <td align="center">FEVE &lt; 35%</td>
                  <td align="center">23,6</td>
                  <td align="center">24,8</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">PSAP &gt; 50 mmHg</td>
                  <td align="center">26,6</td>
                  <td align="center">41,7</td>
                  <td align="center">0,01</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left" rowspan="6">Medica&#231;&#227;o &#224; alta (%)</td>
                  <td align="center">Diur&#233;ticos da al&#231;a</td>
                  <td align="center">96,6</td>
                  <td align="center">97,9</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">Antagonistas dos receptores dos mineralocorticoides</td>
                  <td align="center">42,2</td>
                  <td align="center">46,9</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">IECA/ ARA II</td>
                  <td align="center">86,7</td>
                  <td align="center">76,3</td>
                  <td align="center">&lt; 0,01</td>
                </tr>
                <tr>
                  <td align="center">BB</td>
                  <td align="center">44,5</td>
                  <td align="center">37,3</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">Estatinas</td>
                  <td align="center">40,7</td>
                  <td align="center">35,9</td>
                  <td align="center">NS</td>
                </tr>
                <tr>
                  <td align="center">BB ou IECA</td>
                  <td align="center">69,6</td>
                  <td align="center">66,5</td>
                  <td align="center">NS</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN9">
                <p>ARA II: antagonistas dos receptores da angiotensina II; AVC: acidente vascular cerebral; BB: betabloqueador; BNP: pept&#237;deo natriur&#233;tico cerebral; CCT: cirurgia cardiotor&#225;cica; DRC: doen&#231;a renal cr&#244;nica; IAM: infarto agudo do mioc&#225;rdio; FA: fibrila&#231;&#227;o atrial; FC: frequ&#234;ncia card&#237;aca; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo; HTA: hipertens&#227;o arterial; IECA: inibidores da enzima de convers&#227;o de angiotensina; IMC: &#237;ndice de massa corporal; MDRD: modification of diet in renal disease; PA: press&#227;o arterial; PSAP: press&#227;o sist&#243;lica arterial pulmonar; Distribution Width; PAS: press&#227;o arterial sist&#243;lica; TFGe: taxa de filtra&#231;&#227;o glomerular estimada;</p>
              </fn>
              <fn id="TFN10">
                <label>(*)</label>
                <p>compara&#231;&#227;o entre os grupos.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>RICA score: deriva&#231;&#227;o</title>
          <p>Atribu&#237;ram-se 1 ou 2 pontos (p.) de acordo com os <italic>odds</italic>
						<italic>ratio</italic> (OR) obtidos (p &lt;0,05); 1 ponto se o OR fosse inferior a 1,5 e 2 pontos quando o OR fosse superior a 1,5. O <italic>score</italic> total m&#225;ximo foi de 9 pontos (<xref ref-type="table" rid="t7">Tabela 2</xref>). Ap&#243;s a determina&#231;&#227;o do valor de <italic>score</italic> total, foi estabelecido um <italic>cut-off</italic> de 4 pontos por curva ROC aos 12 meses (<xref ref-type="fig" rid="f05">Figura 2</xref>).Constitu&#237;ram-se 2 grupos de acordo com a pontua&#231;&#227;o, grupo A (n = 195) &lt; 4 pontos <italic>versus</italic> grupo B (n = 142) &#8805; 4 pontos.</p>
          <table-wrap id="t7">
            <label>Tabela 2</label>
            <caption>
              <title>Preditores independentes do endpoint prim&#225;rio (mortalidade e/ou reinterna&#231;&#227;o por insufici&#234;ncia card&#237;aca aos 12 meses de seguimento) por an&#225;lise de regress&#227;o de Cox multivariada</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Vari&#225;veis</th>
                  <th align="center">HR</th>
                  <th align="center">Intervalo de confian&#231;a (95%)</th>
                  <th align="center">Valor de p</th>
                  <th align="center">Score</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Idade &#8805; 75 anos</td>
                  <td align="center">1,7</td>
                  <td align="center">1,1-2,5</td>
                  <td align="center">0,01</td>
                  <td align="center">2</td>
                </tr>
                <tr>
                  <td align="left">Raz&#227;o E/e&#180; &#8805; 15</td>
                  <td align="center">1,6</td>
                  <td align="center">1,1-2,3</td>
                  <td align="center">0,009</td>
                  <td align="center">2</td>
                </tr>
                <tr>
                  <td align="left">BNP&#8805;400 pg/mL</td>
                  <td align="center">1,37</td>
                  <td align="center">1,0-1,9</td>
                  <td align="center">0,04</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">Uremia &#8805; 60 mg/dL</td>
                  <td align="center">1,15</td>
                  <td align="center">1,0-1,5</td>
                  <td align="center">0,04</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">Natremia &lt; 135 mEq/L</td>
                  <td align="center">1,37</td>
                  <td align="center">1,0-1,8</td>
                  <td align="center">0,03</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">Sem IECA/ARA II<xref ref-type="table-fn" rid="TFN12">*</xref> &#224; alta</td>
                  <td align="center">1,9</td>
                  <td align="center">1,2-2,9</td>
                  <td align="center">0,004</td>
                  <td align="center">2</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN11">
                <p>BNP: brain-type natriuretic peptide; IECA/ARA II: inibidores da enzima de convers&#227;o da angiotensina/antagonistas dos receptores da angiotensina II;</p>
              </fn>
              <fn id="TFN12">
                <label>(*)</label>
                <p>se intoler&#226;ncia a IECA.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>
            <fig id="f05">
              <label>Figura 2</label>
              <caption>
                <title>Ap&#243;s a determina&#231;&#227;o do valor de score total, foi estabelecido um cut-off de 4 pontos por curva ROC aos 12 meses.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-107-06-0557-60178-gf02-pt.jpg"/></fig>
          </p>
        </sec>
        <sec>
          <title>RICA score: valida&#231;&#227;o</title>
          <p>Compararam-se os par&#226;metros cl&#237;nicos, anal&#237;ticos, ecocardiogr&#225;ficos e taxa de eventos (morte por qualquer causa e/ou reinterna&#231;&#227;o por IC) aos 6, 12 e 24 meses de seguimento cl&#237;nico entre os 2 grupos.</p>
          <p>Assim, a &#225;rea sob a curva ROC para o <italic>endpoint</italic> (mortalidade e/ou reinterna&#231;&#227;o aos 12 meses) foi de 0,74, sendo o poder de discrimina&#231;&#227;o deste score intermedi&#225;rio. O <italic>score</italic> foi preditor de evento (p &lt;0,001), com capacidade de acur&#225;cia de 65%.</p>
          <p> Na <xref ref-type="table" rid="t8">tabela 3</xref>, encontram-se comparados os dois grupos, separados pelo <italic>score</italic> RICA. O grupo B era constitu&#237;do por doentes mais idosos, com menor &#237;ndice de massa corporal e maior preval&#234;ncia de doen&#231;a renal e anemia. Outros fatores de risco para anemia presentes no grupo de estudo foram o g&#234;nero feminino e a presen&#231;a de DRC.<xref ref-type="bibr" rid="B15">15</xref> Al&#233;m disso, o grupo B apresentou valores de TFGe inferiores ao grupo A (p&lt; 0,001).</p>
          <table-wrap id="t8">
            <label>Tabela 3</label>
            <caption>
              <title>Caracteriza&#231;&#227;o cl&#237;nica de acordo com os grupos de risco</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="40%"/>
                <col width="15%"/>
                <col width="15%"/>
                <col width="15%"/>
                <col width="15%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Caracter&#237;sticas</th>
                  <th align="center">
									</th>
                  <th align="center">Grupo A (n=195)</th>
                  <th align="center">Grupo B (n=142)</th>
                  <th align="center">Valor de p<xref ref-type="table-fn" rid="TFN14">*</xref>
									</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left" rowspan="3">Idade (m&#233;dia &#177; DP)</td>
                  <td align="center">Media</td>
                  <td align="center">75,2&#177;9,6</td>
                  <td align="center">80,1&#177;9,6</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr>
                  <td align="center">Mulheres</td>
                  <td align="center">77,2&#177;8,2</td>
                  <td align="center">81,6&#177;7,9</td>
                  <td align="center">0,05</td>
                </tr>
                <tr>
                  <td align="center">Homens</td>
                  <td align="center">73,3&#177;10,2</td>
                  <td align="center">78,5&#177;11,0</td>
                  <td align="center">0,002</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left">G&#233;nero feminino (%)</td>
                  <td align="center">
									</td>
                  <td align="center">49,2 (n=195)</td>
                  <td align="center">52,1(n=142)</td>
                  <td align="center">0,6</td>
                </tr>
                <tr>
                  <td align="left">IMC (Kg/m<sup>2</sup>) m&#233;dia&#177; DP</td>
                  <td align="center">
									</td>
                  <td align="center">28,2&#177;4,9</td>
                  <td align="center">26,2&#177;5,2</td>
                  <td align="center">0,01</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left">RICA score m&#233;dia&#177; DP</td>
                  <td align="center">
									</td>
                  <td align="center">2,4&#177;1,4</td>
                  <td align="center">5,8&#177;1,3</td>
                  <td align="center">&lt;0,001</td>
                </tr>
                <tr>
                  <td align="left" rowspan="10">Fatores de risco/etiol&#243;gicos e Comorbidades associadas (%)</td>
                  <td align="center">DM</td>
                  <td align="center">38,5</td>
                  <td align="center">32,4</td>
                  <td align="center">0,25</td>
                </tr>
                <tr>
                  <td align="center">HTA</td>
                  <td align="center">72,8</td>
                  <td align="center">57,0</td>
                  <td align="center">0,003</td>
                </tr>
                <tr>
                  <td align="center">DL</td>
                  <td align="center">30,8</td>
                  <td align="center">21,1</td>
                  <td align="center">0,048</td>
                </tr>
                <tr>
                  <td align="center">DAC conhecida</td>
                  <td align="center">36,9</td>
                  <td align="center">38,7</td>
                  <td align="center">0,7</td>
                </tr>
                <tr>
                  <td align="center">EAM pr&#233;vio</td>
                  <td align="center">13,4</td>
                  <td align="center">17,4</td>
                  <td align="center">0,6</td>
                </tr>
                <tr>
                  <td align="center">CCT pr&#233;via</td>
                  <td align="center">4,6</td>
                  <td align="center">10,6</td>
                  <td align="center">0,03</td>
                </tr>
                <tr>
                  <td align="center">AVC</td>
                  <td align="center">9,7</td>
                  <td align="center">7</td>
                  <td align="center">0,38</td>
                </tr>
                <tr>
                  <td align="center">FA</td>
                  <td align="center">50</td>
                  <td align="center">42,3</td>
                  <td align="center">0,03</td>
                </tr>
                <tr>
                  <td align="center">DRC</td>
                  <td align="center">21,0</td>
                  <td align="center">42,3</td>
                  <td align="center">&lt;0,001</td>
                </tr>
                <tr>
                  <td align="center">Anemia</td>
                  <td align="center">37,4</td>
                  <td align="center">57,7</td>
                  <td align="center">&lt;0,001</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left" rowspan="5">Apresenta&#231;&#227;o cl&#237;nica da IC (%)</td>
                  <td align="center">IC descompensada</td>
                  <td align="center">67,7</td>
                  <td align="center">72,5</td>
                  <td align="center" rowspan="5">0,01</td>
                </tr>
                <tr>
                  <td align="center">EAPnh</td>
                  <td align="center">13,3</td>
                  <td align="center">11,3</td>
                </tr>
                <tr>
                  <td align="center">EAPh</td>
                  <td align="center">16,9</td>
                  <td align="center">7,7</td>
                </tr>
                <tr>
                  <td align="center">CC</td>
                  <td align="center">0,5</td>
                  <td align="center">2,8</td>
                </tr>
                <tr>
                  <td align="center">IC direita</td>
                  <td align="center">1,5</td>
                  <td align="center">5,6</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left" rowspan="4">Fatores precipitantes (%)</td>
                  <td align="center">Isquemia/ SCA tipo2</td>
                  <td align="center">11,8</td>
                  <td align="center">14,1</td>
                  <td align="center" rowspan="4">0,03</td>
                </tr>
                <tr>
                  <td align="center">Arritmias card&#237;acas</td>
                  <td align="center">22,1</td>
                  <td align="center">16,9</td>
                </tr>
                <tr>
                  <td align="center">Crise hipertensiva</td>
                  <td align="center">15,9</td>
                  <td align="center">7,0</td>
                </tr>
                <tr>
                  <td align="center">Multifatorial (disfun&#231;&#227;o renal, anemia, infec&#231;&#227;o, m&#225; ades&#227;o terap&#234;utica e &#224; dieta e outros)</td>
                  <td align="center">50,3</td>
                  <td align="center">62,0</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left" rowspan="2">Subtipos de IC (%)</td>
                  <td align="center">IC com FEVE diminu&#237;da</td>
                  <td align="center">47,7</td>
                  <td align="center">59,6</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="center">IC com FEVE preservada</td>
                  <td align="center">52,3</td>
                  <td align="center">40,4</td>
                  <td align="center">
									</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left" rowspan="6">Etiologia de IC (%)</td>
                  <td align="center">Cardiopatia hipertensiva (inclui associada a FA e DM)</td>
                  <td align="center">33,3</td>
                  <td align="center">28,9</td>
                  <td align="center" rowspan="6">0,02</td>
                </tr>
                <tr>
                  <td align="center">CD isqu&#234;mica</td>
                  <td align="center">25,6</td>
                  <td align="center">40,1</td>
                </tr>
                <tr>
                  <td align="center">MCD n&#227;o isqu&#234;mica</td>
                  <td align="center">21,0</td>
                  <td align="center">15,5</td>
                </tr>
                <tr>
                  <td align="center">Doen&#231;a valvular</td>
                  <td align="center">11,8</td>
                  <td align="center">8,5</td>
                </tr>
                <tr>
                  <td align="center">Cor pulmonale</td>
                  <td align="center">3,6</td>
                  <td align="center">6,3</td>
                </tr>
                <tr>
                  <td align="center">Multifatorial</td>
                  <td align="center">4,6</td>
                  <td align="center">0,7</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left">
                    <bold>Par&#226;metros &#224; admiss&#227;o</bold>
                  </td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">PA (m&#233;dia&#177; DP)</td>
                  <td align="center">PAS (mmHg)</td>
                  <td align="center">146,2&#177;30,5</td>
                  <td align="center">130,9&#177;29,5</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr>
                  <td align="center">PAD (mmHg)</td>
                  <td align="center">83,7&#177;19,9</td>
                  <td align="center">75,4&#177;16,0</td>
                  <td align="center">&lt;0,001</td>
                </tr>
                <tr>
                  <td align="left">Laboratoriais</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">TFGe CG (ml/min) m&#233;dia&#177; DP</td>
                  <td align="center">51,0&#177;21,8</td>
                  <td align="center">37,7&#177;17</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">TFGe MDRD &lt; 60 ml/min/1,73m<sup>2</sup> (%)</td>
                  <td align="center">21</td>
                  <td align="center">42,3</td>
                  <td align="center">&lt;0,001</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">S&#243;dio &lt; 135 mmol/L (%)</td>
                  <td align="center">7,7</td>
                  <td align="center">29,6</td>
                  <td align="center">&lt; 0,01</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">Pot&#225;ssio (mmol/L) m&#233;dia&#177; DP</td>
                  <td align="center">4,5&#177;0,6</td>
                  <td align="center">4,7&#177;0,7</td>
                  <td align="center">&lt; 0,01</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">Hemoglobina (g/dL) m&#233;dia&#177; DP</td>
                  <td align="center">13,0&#177;2,0</td>
                  <td align="center">12,2&#177;2,1</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr>
                  <td align="left">Continua&#231;&#227;o</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">RDW &gt; 15 (%)</td>
                  <td align="center">49,7</td>
                  <td align="center">68,3</td>
                  <td align="center">0,02</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">BNP &gt; 400 pg/mL &#224; admiss&#227;o (%)</td>
                  <td align="center">31,8</td>
                  <td align="center">43,7</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">BNP &gt; 400 pg/mL &#224; alta (%)</td>
                  <td align="center">10,3</td>
                  <td align="center">37,3</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">PCR (mg/dL) m&#233;dia&#177; DP</td>
                  <td align="center">1,8&#177;2,4</td>
                  <td align="center">2,5&#177;3,4</td>
                  <td align="center">0,02</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left">Ecocardiogr&#225;ficas</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">FEVE m&#233;dia (%)</td>
                  <td align="center">50,1&#177;15,1</td>
                  <td align="center">46,0&#177;16,8</td>
                  <td align="center">0,02</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">FEVE 30% (%)</td>
                  <td align="center">10,8</td>
                  <td align="center">17,0</td>
                  <td align="center">0,04</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">FEVE 30-44% (%)</td>
                  <td align="center">28,7</td>
                  <td align="center">35,5</td>
                  <td align="center">0,04</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">FEVE &#8805; 50% (%)</td>
                  <td align="center">52,3</td>
                  <td align="center">40,4</td>
                  <td align="center">0,04</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">PSAP (mmHg) m&#233;dia&#177; DP</td>
                  <td align="center">42,2&#177;12,9</td>
                  <td align="center">50,0&#177;14,7</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr style="border-top-width:thin;border-top-style:solid">
                  <td align="left">Medica&#231;&#227;o &#224; alta</td>
                  <td align="center">BB</td>
                  <td align="center">46,2</td>
                  <td align="center">33,1</td>
                  <td align="center">0,02</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">IECA</td>
                  <td align="center">68,7</td>
                  <td align="center">52,1</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">ARAII</td>
                  <td align="center">24,1</td>
                  <td align="center">12,7</td>
                  <td align="center">&lt; 0,001</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">BB+ IECA/ARAII</td>
                  <td align="center">44,1</td>
                  <td align="center">23,9</td>
                  <td align="center">0,04</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">Furosemida</td>
                  <td align="center">95,4</td>
                  <td align="center">96,5</td>
                  <td align="center">0,6</td>
                </tr>
                <tr>
                  <td align="left">
									</td>
                  <td align="center">Espironolactona</td>
                  <td align="center">39</td>
                  <td align="center">46,5</td>
                  <td align="center">0,1</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN13">
                <p>ARA II: antagonistas dos recetores da angiotensina II; AVC: acidente vascular cerebral; BB: betabloqueador; BNP: pept&#237;deo natriur&#233;tico cerebral; CCT: cirurgia cardiotor&#225;cica; CC: choque cardiog&#234;nico; CD: cardiopatia dilatada; CG: Cockcroft-Gault; DAC: doen&#231;a arterial coron&#225;ria; DL: dislipidemia; DM: diabetes mellitus; DP: desvio-padr&#227;o; DRC: doen&#231;a renal cr&#243;nica; EAM: enfarte agudo do mioc&#225;rdio; EAP h: edema agudo do pulm&#227;o hipertensivo; EAP nh: edema agudo do pulm&#227;o n&#227;o hipertensivo; FA: fibrila&#231;&#227;o atrial; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo; FRCV: fatores de risco cardiovasculare; HTA: hipertens&#227;o arterial; IC: insufici&#234;ncia card&#237;aca; IECA: inibidores da enzima de convers&#227;o de angiotensina; IMC: &#237;ndice de massa corporal; MCD: miocardiopatia dilatada; MDRD: Modification of Diet in Renal Disease; PA: press&#227;o arterial; PAD: press&#227;o arterial diast&#243;lica; PAS: press&#227;o arterial sist&#243;lica; PCR: protein chain reaction; PSAP: press&#227;o sist&#243;lica arterial pulmonar; RDW: Red cell Distribution Width; RICA: registo de insufici&#234;ncia card&#237;aca aguda; SCA: s&#237;ndrome coron&#225;ria aguda; TFGe: taxa de filtra&#231;&#227;o glomerular estimada;</p>
              </fn>
              <fn id="TFN14">
                <label>(*)</label>
                <p>compara&#231;&#227;o entre os grupos de risco (A e B).</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>Quanto &#224;s altera&#231;&#245;es eletrocardiogr&#225;ficas, o predominou no grupo A, enquanto que outro ritmo n&#227;o sinusal foi predominante no grupo B (p&lt; 0,01). N&#227;o se verificaram diferen&#231;as estatisticamente significativas quanto &#224; dura&#231;&#227;o da condu&#231;&#227;o intraventricular (QRS) entre os grupos.</p>
          <p>A identifica&#231;&#227;o do fator precipitante &#233; fundamental para a estabiliza&#231;&#227;o do doente.<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref> No nosso estudo, o fator precipitante mais frequente foi multifatorial (incluindo a m&#225; ades&#227;o &#224; dieta e &#224; terap&#234;utica) em ambos os grupos.</p>
          <p>A etiologia da IC mais frequente no grupo B foi a cardiopatia isqu&#234;mica (40,1%).</p>
          <p>Encontramos no grupo B uma elevada propor&#231;&#227;o de idosos que n&#227;o aderiram ao esquema terap&#234;utico e posol&#243;gico com betabloqueadores proposto.</p>
          <p>No grupo B, cerca de 40% dos doentes apresentavam FEVE superior a 50%. Outros par&#226;metros ecocardiogr&#225;ficos encontram-se discriminados na <xref ref-type="table" rid="t8">tabela 3</xref>.</p>
          <p>De maior relev&#226;ncia e com impacto progn&#243;stico, foi a medica&#231;&#227;o introduzida ainda na fase hospitalar. &#192; alta, cerca de 52% dos doentes do grupo B estavam medicados com IECA e 46% com espironolactona, sendo que 20% dos doentes apresentava FEVE inferior a 30%. A medica&#231;&#227;o &#224; data de alta est&#225; explicitada na <xref ref-type="table" rid="t8">tabela 3</xref>.</p>
          <p>A dura&#231;&#227;o m&#233;dia da interna&#231;&#227;o foi de 8,6 &#177; 7 dias atingindo uma m&#233;dia de 10 (&#177;7,7) dias no grupo B.</p>
          <p>RICA score como preditor de eventos durante o per&#237;odo de seguimento cl&#237;nico</p>
          <p>As taxas de reinterna&#231;&#245;es aos 6, 12 e 24 meses est&#227;o expressas na <xref ref-type="table" rid="t9">tabela 4</xref>.</p>
          <table-wrap id="t9">
            <label>Tabela 4</label>
            <caption>
              <title>Taxa de reinterna&#231;&#227;o por insufici&#234;ncia card&#237;aca aos 6, 12 e 24 meses segundo os grupos</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Reinterna&#231;&#227;o (%)</th>
                  <th align="center">Grupo A</th>
                  <th align="center">Grupo B</th>
                  <th align="center">OR (IC 95%)</th>
                  <th align="center">Valor de p</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">6 meses</td>
                  <td align="center">21,5</td>
                  <td align="center">30,5</td>
                  <td align="center">1,6 (1,2-2,6)</td>
                  <td align="center">0,04</td>
                </tr>
                <tr>
                  <td align="left">12 meses</td>
                  <td align="center">34,7</td>
                  <td align="center">44,4</td>
                  <td align="center">1,6 (1,2- 2,5)</td>
                  <td align="center">0,04</td>
                </tr>
                <tr>
                  <td align="left">24 meses</td>
                  <td align="center">48,2</td>
                  <td align="center">58,7</td>
                  <td align="center">1,5 (0,9-2,4)</td>
                  <td align="center">0,06</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <p>Em cerca de um quarto dos casos, os pacientes pertencentes ao grupo B foram reinternados em um per&#237;odo de 90 dias ap&#243;s a alta hospitalar.</p>
          <p>Aproximadamente 25% dos doentes do grupo A e 50% dos doentes do grupo B atingiram o <italic>endpoint</italic> aos 6 meses ap&#243;s a alta hospitalar (p&lt;0,001). O grupo B apresentou menor sobrevida aos 6 e 24 meses comparativamente ao grupo A (p&lt;0,001). Contudo, em ambos os grupos observou-se que a taxa de reinterna&#231;&#227;o por IC descompensada e/ou mortalidade por qualquer causa foi mais acentuada nos tr&#234;s meses seguintes &#224; alta hospitalar, conforme indicado nas curvas de Kaplan Meier ilustradas na <xref ref-type="fig" rid="f06">figura 3 (A</xref>, <xref ref-type="fig" rid="f06">B</xref> e <xref ref-type="fig" rid="f06">C)</xref>.</p>
          <p>
            <fig id="f06">
              <label>Figura 3</label>
              <caption>
                <title>A; B e C) Curvas de Kaplan Meier que demonstram a taxa de endpoint combinado (mortalidade e/ou reinterna&#231;&#227;o) do grupo A (score&lt; 4) e grupo B (score &gt; 4) aos 6, 12 e 24 meses de seguimento cl&#237;nico, respeti vamente.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-107-06-0557-60178-gf03-pt.jpg"/></fig>
          </p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Neste estudo retrospectivo, construiu-se um novo score de risco de eventos a m&#233;dio prazo em doentes que s&#227;o internados por s&#237;ndromes de IC aguda. A inclus&#227;o de quatro vari&#225;veis previamente identificadas em modelos de risco e a identifica&#231;&#227;o de duas novas vari&#225;veis - raz&#227;o E/e' e a aus&#234;ncia de prescri&#231;&#227;o de iECA/ARA (se intolerantes a IECA) &#224; data de alta - permitiram identificar um grupo de elevado risco, com <italic>score</italic> superior a 4 (grupo B). Esse grupo era majoritariamente constitu&#237;do por idosos com maior n&#250;mero de comorbidades, maior instabilidade hemodin&#226;mica &#224; admiss&#227;o, maior grau de disfun&#231;&#227;o ventricular esquerda e pior progn&#243;stico a curto, m&#233;dio e longo prazo.</p>
        <p>A identifica&#231;&#227;o e caracteriza&#231;&#227;o cl&#237;nica de um grupo em maior risco de eventos permite uma abordagem multidisciplinar mais precoce, promovendo a identifica&#231;&#227;o correta dos fatores de descompensa&#231;&#227;o, maior ades&#227;o &#224; terap&#234;utica, e redu&#231;&#227;o do tempo de interna&#231;&#227;o, de morbimortalidade e readmiss&#227;o hospitalar, que consomem a maior parte dos recursos envolvidos nessa s&#237;ndrome.<xref ref-type="bibr" rid="B5">5</xref>
				</p>
        <p>Quatro das vari&#225;veis inclu&#237;das no <italic>score</italic> por n&#243;s desenvolvido est&#227;o presentes em muitos modelos. No entanto, a inclus&#227;o de uma vari&#225;vel ecocardiogr&#225;fica (raz&#227;o E/e') determinada durante o internamento e outra vari&#225;vel determinada &#224; data de alta (aus&#234;ncia de prescri&#231;&#227;o de IECA/ARA) confere originalidade ao nosso trabalho. Tal como em modelos pr&#233;vios, este <italic>score</italic> permitiu identificar um grupo de maior risco, mais idoso e com maior n&#250;mero de comorbidades, nomeadamente s&#237;ndrome cardiorrenal.</p>
        <p>Os modelos de risco utilizados nas s&#237;ndromas de IC aguda apresentam v&#225;rias particularidades. Em primeiro lugar, os doentes s&#227;o avaliados na interna&#231;&#227;o ou no servi&#231;o de urg&#234;ncia, em que habitualmente se prioriza a avalia&#231;&#227;o do risco a muito curto prazo (intra-hospitalar) ou a curto-m&#233;dio prazo (entre 2 e 6 meses ap&#243;s a alta), j&#225; que a identifica&#231;&#227;o de doentes de alto risco ajudaria a fazer um seguimento mais estreito e a intensificar os tratamentos nesse per&#237;odo em que se encontram mais vulner&#225;veis.<xref ref-type="bibr" rid="B18">18</xref> Por esta raz&#227;o, as vari&#225;veis destes modelos, ainda que similares &#224;s dos scores de IC cr&#244;nica, diferem ligeiramente, dando mais import&#226;ncia a fatores cl&#237;nicos, demogr&#225;ficos e anal&#237;ticos f&#225;ceis e rapidamente acess&#237;veis.<xref ref-type="bibr" rid="B18">18</xref>
				</p>
        <p>Neste trabalho, pretendeu-se avaliar o risco a m&#233;dio prazo (12 meses), com a inclus&#227;o de uma vari&#225;vel diferente da maioria dos modelos: a aus&#234;ncia de prescri&#231;&#227;o de IECA/ARA (se intoler&#226;ncia a IECA) &#224; data da alta hospitalar. Embora o <italic>endpoint</italic> mortalidade intra-hospitalar ou a 90 dias pare&#231;a mais relevante em s&#237;ndromes agudas como a IC aguda, n&#227;o pode ser ignorado o seguimento cl&#237;nico a longo prazo com a inclus&#227;o de vari&#225;veis, como a terap&#234;utica baseada na evid&#234;ncia cujo impacto no progn&#243;stico &#233; mais tardio.</p>
        <p>Existem na literatura v&#225;rios modelos progn&#243;sticos, desenvolvidos no &#226;mbito de IC aguda, que podem ser classificados em 3 grupos: cinco modelos realizados com registro de doentes internados, um modelo que inclui doentes internados provenientes de ensaios cl&#237;nicos e dois modelos realizados no servi&#231;o de urg&#234;ncia. Na <xref ref-type="table" rid="t10">tabela 5</xref>, apresenta-se um resumo dos modelos progn&#243;sticos na IC aguda.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref><sup>-</sup><xref ref-type="bibr" rid="B25">25</xref> Tr&#234;s marcadores inclu&#237;dos no <italic>score</italic> criado por n&#243;s - a idade, a natremia e a uremia - s&#227;o comuns &#224; maioria destes modelos. O progn&#243;stico da IC aguda agrava progressivamente com a idade, pelo efeito da idade em si mesma e por sua associa&#231;&#227;o a uma maior comorbidade e fragilidade.<xref ref-type="bibr" rid="B26">26</xref> A insufici&#234;ncia renal &#233; comum em doentes com IC aguda. Alguns estudos referem que os n&#237;veis elevados de ureia triplicam o risco de mortalidade intra-hospitalar e mortalidade p&#243;s-alta.<xref ref-type="bibr" rid="B10">10</xref> Relativamente &#224; hiponatremia, um achado habitual nos pacientes com IC descompensada, ap&#243;s an&#225;lise multivariada, concluiu-se que para uma natremia inferior a 140 mmol/L, o decr&#233;scimo em 3 mmol/L aumenta o risco de mortalidade intra-hospitalar em 19,5%.<xref ref-type="bibr" rid="B9">9</xref>
				</p>
        <table-wrap id="t10">
          <label>Tabela 5</label>
          <caption>
            <title>Modelos progn&#243;sticos na insufici&#234;ncia card&#237;aca C aguda<xref ref-type="table-fn" rid="TFN16">*</xref>
						</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Autor</th>
                <th align="center">Ano de publica&#231;&#227;o</th>
                <th align="center">Corte de deriva&#231;&#227;o (n)</th>
                <th align="center">Corte de valida&#231;&#227;o (n)</th>
                <th align="center">Vari&#225;veis (n)</th>
                <th align="center">Resultado/AUC</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>ADHERE<xref ref-type="bibr" rid="B6">6</xref> Fonarrow</td>
                <td align="center">2005</td>
                <td align="center">Multic&#234;ntrico Internacional (33 046)</td>
                <td align="center">Multic&#234;ntrico (32.229)</td>
                <td align="center">Idade, Cl&#237;nicas Laboratoriais (4)</td>
                <td align="center">MIH/ 0,75</td>
              </tr>
              <tr>
                <td>AHFI <xref ref-type="bibr" rid="B19">19</xref> Auble</td>
                <td align="center">2005 (deriva&#231;&#227;o) 2008 (valida&#231;&#227;o)</td>
                <td align="center">Multic&#234;ntrico Nacional (33 533)</td>
                <td align="center">Amostra aleatorizada (8384)</td>
                <td align="center">Demogr&#225;ficas Cl&#237;nicas Laboratoriais Testes diagn&#243;sticos n&#227;o invasivos (21)</td>
                <td align="center">MIH/ 0,59</td>
              </tr>
              <tr>
                <td>GWTG-HF <xref ref-type="bibr" rid="B21">21</xref>Peterson</td>
                <td align="center">2010</td>
                <td align="center">Comunit&#225;rio Multic&#234;ntrico Internacional (27 850)</td>
                <td align="center">Comunit&#225;rio Multic&#234;ntrico (11 933)</td>
                <td align="center">Demogr&#225;ficas Cl&#237;nicas Laboratoriais Comorbidades (7)</td>
                <td align="center">MIH / 0,75</td>
              </tr>
              <tr>
                <td>EFFECT <xref ref-type="bibr" rid="B22">22</xref> Lee</td>
                <td align="center">2003</td>
                <td align="center">Multic&#234;ntrico Nacional (2624)</td>
                <td align="center">Comunit&#225;rio Multic&#234;ntrico (1407)</td>
                <td align="center">Demogr&#225;ficas Cl&#237;nicas Laboratoriais Comorbidades (10)</td>
                <td align="center">Mortalidade aos 30 dias/0,79 Mortalidade a um ano/0,76</td>
              </tr>
              <tr>
                <td>OPTIMIZE-HF <xref ref-type="bibr" rid="B20">20</xref> O'Connor</td>
                <td align="center">2008</td>
                <td align="center">Registo Multic&#234;ntrico Internacional (4402)</td>
                <td align="center">OPTIME CHF (949) y ESCAPE (433)</td>
                <td align="center">Demogr&#225;ficas Cl&#237;nicas Laboratoriais Comorbidades (13)</td>
                <td align="center">Mortalidade a 60-90 dias/0,72</td>
              </tr>
              <tr>
                <td>OPTIMIZE-HF <xref ref-type="bibr" rid="B5">5</xref> Abraham</td>
                <td align="center">2008</td>
                <td align="center">Registo Multic&#234;ntrico Internacional (37 548)</td>
                <td align="center"><italic>Bootstrapping</italic> interno Ensaio ADHERE (181 830)</td>
                <td align="center">Demogr&#225;ficas Cl&#237;nicas Laboratoriais Disfun&#231;&#227;o sist&#243;lica (7)</td>
                <td align="center">MIH/ 0,74</td>
              </tr>
              <tr>
                <td>OPTIME CHF <xref ref-type="bibr" rid="B23">23</xref> Felker</td>
                <td align="center">2004</td>
                <td align="center">Multic&#234;ntrico Internacional (949)</td>
                <td align="center"><italic>Bootstrapping</italic> interno</td>
                <td align="center">Demogr&#225;ficas Cl&#237;nicas Laboratoriais (5)</td>
                <td align="center">Mortalidade a 60 dias/0,77</td>
              </tr>
              <tr>
                <td>Otawa <xref ref-type="bibr" rid="B24">24</xref> Stiell</td>
                <td align="center">2013</td>
                <td align="center">Comunit&#225;rio Multic&#234;ntrico Nacional (507)</td>
                <td align="center"><italic>Bootstrapping</italic> interno</td>
                <td align="center">Cl&#237;nicas Laboratoriais (10)</td>
                <td align="center">Mortalidade aos 30 dias ou evento n&#227;o fatal aos 14 dias/BNP 0,77, n&#227;o BNP 0,75</td>
              </tr>
              <tr>
                <td>EHRMG <xref ref-type="bibr" rid="B25">25</xref> Lee</td>
                <td align="center">2012</td>
                <td align="center">Comunit&#225;rio Multic&#234;ntrico Nacional (7433)</td>
                <td align="center">Comunit&#225;rio Multic&#234;ntrico (5.158)</td>
                <td align="center">Cl&#237;nicas Laboratoriais Comorbidades (10)</td>
                <td align="center">Mortalidade 7 dias/0,8</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN15">
              <p>AUC: &#225;rea sob a curva; ADHERE: Acute Decompensated Heart Failure National Registry; AHFI: Acute Heart Failure Index; EFFECT: Enhanced Feedback for Effective Cardiac Treatment; EHMRG: Emergency Heart Failure Mortality Risk; GWTG-HF: Get With the Guidelines-Heart Failure; OPTIMIZE-HF: Organized Program to initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure; OPTIME-CHF: Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure; Ottawa: Ottawa Heart Failure Risk Model;</p>
            </fn>
            <fn id="TFN16">
              <label>(*)</label>
              <p>Adaptado de Ferrero P, et al. Int J Cardiol. 2015;188:1-920<xref ref-type="bibr" rid="B18">18</xref>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Apesar da disponibilidade cada vez mais generalizada e da utilidade progn&#243;stica comprovada dos pept&#237;deos natriur&#233;ticos, esses n&#227;o constam na maioria dos modelos preditores de risco. Alguns estudos sugerem que um incremento de 30% nos valores normais de NT-proBNP &#224; admiss&#227;o multiplica em 6 vezes o risco de nova hospitaliza&#231;&#227;o.<xref ref-type="bibr" rid="B27">27</xref>
				</p>
        <p>A avalia&#231;&#227;o por doppler tecidular da rela&#231;&#227;o entre a velocidade do anel mitral e das curvas de velocidade do fluxo transmitral (raz&#227;oE/e&#180;) revelou-se um preditor independente de mortalidade ao ano em doentes internados por IC aguda.<xref ref-type="bibr" rid="B28">28</xref>
				</p>
        <p>Apesar de n&#227;o existirem dados na literatura que evidenciem o benef&#237;cio da introdu&#231;&#227;o precoce de IECA na IC aguda nas primeiras horas ap&#243;s admiss&#227;o hospitalar, a sua prescri&#231;&#227;o &#233; mandat&#243;ria nas 48 h a 72 horas ap&#243;s internamento, com benef&#237;cios comprovados, em termos de redu&#231;&#227;o de mortalidade e taxa de reinterna&#231;&#227;o, de acordo com a recomenda&#231;&#245;es da Sociedade Europeia de Cardiologia.<xref ref-type="bibr" rid="B3">3</xref>
				</p>
        <p>Apesar de in&#250;meros estudos o demonstrarem, a falta de prescri&#231;&#227;o de betabloqueadores &#224; data de alta n&#227;o foi, neste trabalho, um fator preditor de mortalidade e/ou reinterna&#231;&#227;o por IC, possivelmente por um vi&#233;s de sele&#231;&#227;o.</p>
        <p>O risco estimado &#224; admiss&#227;o pode ajudar a decidir se o doente &#233; candidato a tratamento intensivo ou n&#227;o. Contudo, v&#225;rios estudos t&#234;m demonstrado que os scores de risco estimados &#224; data de alta (incluindo biomarcadores e terap&#234;utica prescrita &#224; alta) apresentam melhor valor progn&#243;stico em rela&#231;&#227;o aos determinados &#224; admiss&#227;o.<xref ref-type="bibr" rid="B29">29</xref> As ferramentas de previs&#227;o de risco s&#227;o imprescind&#237;veis para determinar o progn&#243;stico da IC. Embora estes modelos de risco possam pontuar com precis&#227;o o progn&#243;stico na IC aguda a curto-prazo, devem ser testados extensivamente em doentes idosos ou com m&#250;ltiplas comorbidades.<xref ref-type="bibr" rid="B29">29</xref> Al&#233;m disso, estudos prospectivos, randomizados, s&#227;o necess&#225;rios a fim de determinar o impacto da estratifica&#231;&#227;o de risco a longo prazo nos doentes com IC aguda.<xref ref-type="bibr" rid="B29">29</xref>
				</p>
        <sec>
          <title>Limita&#231;&#245;es</title>
          <p>Algumas limita&#231;&#245;es inerentes &#224; cria&#231;&#227;o deste score devem ser consideradas na interpreta&#231;&#227;o dos seus resultados. O fato de se tratar de um estudo retrospectivo possibilita o aparecimento de vi&#233;s de sele&#231;&#227;o. Ser&#225; necess&#225;ria uma valida&#231;&#227;o externa do modelo, preferencialmente em outro centro. O diagn&#243;stico da IC aguda foi baseado apenas nos crit&#233;rios da Sociedade Europeia de Cardologia e n&#227;o foi definida a data de in&#237;cio dos sintomas, n&#227;o sendo poss&#237;vel diferenciar a IC aguda <italic>de novo</italic> da IC cr&#244;nica agudizada. Al&#233;m disso, por haver heterogeneidade da popula&#231;&#227;o, a an&#225;lise do tratamento e progn&#243;stico exigir&#225; ajuste. Outra limita&#231;&#227;o prende-se ao fato de n&#227;o terem sido inclu&#237;dos doentes que tiveram alta para o domic&#237;lio diretamente do servi&#231;o de urg&#234;ncia. Ainda, o n&#250;mero de dados faltantes foi elevado para algumas vari&#225;veis de preenchimento n&#227;o obrigat&#243;rio, interferindo nos resultados encontrados. A ecocardiografia n&#227;o foi realizada &#224; admiss&#227;o, mas alguns dias ap&#243;s a interna&#231;&#227;o, o que poder&#225; influir nas medi&#231;&#245;es que foram efetuadas para derivar o <italic>score</italic>.</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#245;es</title>
        <p>Neste estudo, constru&#237;mos um novo <italic>score</italic> de risco de eventos a m&#233;dio prazo em pacientes internados por s&#237;ndromes de IC aguda. A inclus&#227;o de quatro vari&#225;veis previamente identificadas em modelos de risco e a identifica&#231;&#227;o de mais duas vari&#225;veis: raz&#227;o E/e' e a aus&#234;ncia de prescri&#231;&#227;o de iECA/ARA &#224; data de alta, permitiram identificar um grupo de elevado risco de mortalidade por qualquer causa ou reinterna&#231;&#227;o por IC aos 12 meses ap&#243;s a alta. Tal grupo (grupo B), com score superior a 4, era maioritariamente constitu&#237;do por idosos, com maior n&#250;mero de comorbidades, maior instabilidade hemodin&#226;mica &#224; admiss&#227;o, maior grau de disfun&#231;&#227;o ventricular esquerda e pior progn&#243;stico a curto, m&#233;dio e longo prazo.</p>
        <p>Este grupo de maior risco que poder&#225; beneficiar de uma monitoriza&#231;&#227;o mais apertada e institui&#231;&#227;o precoce de terap&#234;utica baseada na evid&#234;ncia.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>Fontes de financiamento</p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
      </fn-group>
      <fn-group>
        <fn fn-type="other">
          <p>Vincula&#231;&#227;o acad&#234;mica</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>
