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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">ABC HF</journal-id>
<journal-title-group>
<journal-title>ABC: Heart Failure &#x26; Cardiomyopathy</journal-title>
<abbrev-journal-title abbrev-type="publisher">ABC Heart Fail Cardiomyop</abbrev-journal-title></journal-title-group>
<issn pub-type="epub">0000-0000</issn>
<publisher>
<publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name></publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">abchf.20210011</article-id>
<article-id pub-id-type="doi">10.36660/abchf.20210011</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Brief Communication</subject></subj-group></article-categories>
<title-group>
<article-title>The Challenge of HFpEF Diagnosis in Brazil</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-5774-2780</contrib-id>
<name><surname>Danzmann</surname><given-names>Luiz Cl&#xE1;udio</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref> <xref ref-type="corresp" rid="c1"/></contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0001-9940-0829</contrib-id>
<name><surname>Belyavskiy</surname><given-names>Evgeny</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0003-0034-4981</contrib-id>
<name><surname>Jorge</surname><given-names>Ant&#xF4;nio Jos&#xE9; Lagoeiro</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-7452-3870</contrib-id>
<name><surname>Mesquita</surname><given-names>Evandro Tinoco</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-5357-9138</contrib-id>
<name><surname>Torres</surname><given-names>Marco Antonio Rodrigues</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib>
<aff id="aff1">
<label>1</label>
<institution content-type="orgname">Universidade Luterana do Brasil</institution>
<addr-line>
<named-content content-type="city">Canoas</named-content>
<named-content content-type="state">RS</named-content></addr-line>
<country country="BR">Brazil</country>
<institution content-type="original">Universidade Luterana do Brasil (ULBRA), Canoas, RS - Brazil</institution></aff>
<aff id="aff2">
<label>2</label>
<institution content-type="orgname">Hospital S&#xE3;o Lucas da PUC-RS</institution>
<addr-line>
<named-content content-type="city">Porto Alegre</named-content>
<named-content content-type="state">RS</named-content></addr-line>
<country country="BR">Brazil</country>
<institution content-type="original">Hospital S&#xE3;o Lucas da PUC-RS, Porto Alegre, RS - Brazil</institution></aff>
<aff id="aff3">
<label>3</label>
<institution content-type="orgname">Universit&#xE4;tsmedizin Berlin</institution>
<institution content-type="orgdiv1">Campus Virchow-Klinikum Charit&#xE9;</institution>
<institution content-type="orgdiv2">Department of Internal Medicine and Cardiology</institution>
<country country="DE">Germany</country>
<institution content-type="original">Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum Charit&#xE9;, Universit&#xE4;tsmedizin Berlin - Germany</institution></aff>
<aff id="aff4">
<label>4</label>
<institution content-type="orgname">German Center for Cardiovascular Research</institution>
<country country="DE">Germany</country>
<institution content-type="original">German Center for Cardiovascular Research (DZHK), partner site Berlin - Germany</institution></aff>
<aff id="aff5">
<label>5</label>
<institution content-type="orgname">Universidade Federal Fluminense</institution>
<addr-line>
<named-content content-type="city">Niter&#xF3;i</named-content>
<named-content content-type="state">RJ</named-content></addr-line>
<country country="BR">Brazil</country>
<institution content-type="original">Universidade Federal Fluminense (UFF), Niter&#xF3;i, RJ - Brazil</institution></aff>
<aff id="aff6">
<label>6</label>
<institution content-type="orgname">Universidade Federal do Rio Grande do Sul</institution>
<institution content-type="orgdiv1">Programa de P&#xF3;s-Gradua&#xE7;&#xE3;o em Ci&#xEA;ncias Pneumol&#xF3;gicas</institution>
<addr-line>
<named-content content-type="city">Porto Alegre</named-content>
<named-content content-type="state">RS</named-content></addr-line>
<country country="BR">Brazil</country>
<institution content-type="original">Programa de P&#xF3;s-Gradua&#xE7;&#xE3;o em Ci&#xEA;ncias Pneumol&#xF3;gicas da Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS - Brazil</institution></aff></contrib-group>
<author-notes>
<corresp id="c1"><bold>Mailing Address: Luiz Claudio Danzmann</bold> &#x2022; Rua Visconde do Herval, 472/903. Postal Code <postal-code>90130-150</postal-code>, Porto Alegre, RS &#x2013; Brazil. E-mail: <email>luiz.danzmann@ulbra.br</email></corresp>
<fn fn-type="conflict">
<p><bold>Potential Conflict of Interest</bold></p>
<p>No potential conflict of interest relevant to this article was reported.</p></fn>
<fn fn-type="con">
<p><bold>Author Contributions</bold></p>
<p>Conception and design of the research, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Danzmann LC, Belyavskiy E, Jorge AJL, Mesquita ET, Torres MAR; Acquisition of data and Analysis and interpretation of the data: Danzmann LC, Jorge AJL, Mesquita ET; Statistical analysis and Obtaining financing: Danzmann LC.</p></fn></author-notes>
<pub-date publication-format="electronic" date-type="pub">
<day>06</day>
<month>07</month>
<year>2021</year></pub-date>
<pub-date publication-format="electronic" date-type="collection">
<season>Jul-Sep</season>
<year>2021</year></pub-date>
<volume>1</volume>
<issue>1</issue>
<fpage>63</fpage>
<lpage>66</lpage>
<history>
<date date-type="received">
<day>28</day>
<month>04</month>
<year>2021</year></date>
<date date-type="rev-recd">
<day>10</day>
<month>05</month>
<year>2021</year></date>
<date date-type="accepted">
<day>01</day>
<month>06</month>
<year>2021</year></date>
</history>
<permissions>
<license license-type="open-access" xml:lang="en" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p></license></permissions>
<abstract>
<title>Abstract</title>
<p>Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in Brazil and worldwide. However, the recent diagnostic criteria for this condition are complex and difficult to apply in the Brazilian health system. This review proposes adapting the modern diagnostic criteria to the needs of each patient, from the primary care to the most complex one, using a system of three steps of complexity and highlighting the importance of searching specific disease etiology.</p></abstract>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>Heart Failure/ophysiopathology</kwd>
<kwd>Stroke Volume</kwd>
<kwd>Diagnostic Imaging</kwd>
<kwd>Echocardiography/methods</kwd>
<kwd>Dyspmea</kwd>
<kwd>Fatigue</kwd>
<kwd>Vascular Stiffness</kwd>
<kwd>Comorbidity</kwd></kwd-group>
<counts>
<fig-count count="6"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="7"/>
<page-count count="4"/></counts></article-meta></front>
<body>
<p>Heart failure with preserved ejection fraction (HFpEF) remains a major public health problem worldwide and also in Brazil.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> The recognition and diagnosis of this syndrome remain a challenge, due to its physiopathological complexity and phenotypic diversity.</p>
<p>The current scientific evidence on etiopathogenesis provided more accurate diagnostic recommendations but requires comprehensive echocardiographic analysis.<xref ref-type="bibr" rid="B2"><sup>2</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B3"><sup>3</sup></xref> A recently published recommendation from the Heart Failure Association of the European Society of Cardiology (HFA-ESC) brought a comprehensive overview and an algorithm for the diagnosis of HFpEF.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref></p>
<sec>
<title>Four basic elements for the diagnosis of HFpEF are:</title>
<list list-type="order">
<list-item>
<p>Recognition of typical signs and symptoms (e.g. dyspnea, fatigue, reduced exercise tolerance, and signs of congestion) and comorbidities related to HF;<xref ref-type="bibr" rid="B5"><sup>5</sup></xref></p></list-item>
<list-item>
<p>Preserved left ventricular systolic function, i.e., ejection fraction (LVEF) &#x2265; 50%;</p></list-item>
<list-item>
<p>Left atrium and left ventricle (LV) remodeling;</p></list-item>
<list-item>
<p>Direct or indirect evidence of high left ventricular filling pressure.</p></list-item></list>
</sec>
<sec>
<title>Diagnosis based on three steps</title>
<p>In a recently published article,<xref ref-type="bibr" rid="B6"><sup>6</sup></xref> we propose a compilation of the Brazilian Society of Cardiology (SBC) Guidelines, Mayo Clinic, and HFA-ESC criteria adapted to the national health system. It recommends an approach in three degrees of complexity, adapting the use of resources from primary care (step 1) to the high complexity health centers (steps 2 and 3) (<xref ref-type="fig" rid="f1">Figure 1</xref>).</p>
<fig id="f1">
<label>Figure 1</label>
<caption>
<title>Diagnostic algorithm for HFpEF. HF: heart failure; LVEF: left ventricular ejection fraction.</title></caption>
<graphic xlink:href="0000-0000-abchf-001-01-0063-gf01.tif"/></fig>
<sec>
<title>Step 1: Pre-test clinical approach.</title>
<list list-type="bullet">
<list-item>
<p>Anamnesis: identification of signs and symptoms that offer the possibility of HF;</p></list-item>
<list-item>
<p>Comorbidities: diagnosis of the clinical characteristics and major morbidities associated with risk of HFpEF, such as age &#x3E; 60 years, female sex, obesity, hypertension, diabetes, ischemic heart disease, and atrial fibrillation.</p></list-item>
<list-item>
<p>Agonist or competing comorbidities of HF: agonists to decreased functional capacity, or are a differential diagnosis, such as anemia, chronic obstructive pulmonary disease, asthma, pulmonary fibrosis, peripheral arterial disease, sarcopenia, thyroid diseases, nephropathies, and electrolyte imbalance.</p></list-item>
<list-item>
<p>Basic tests: blood cell count, creatinine, urea, glycemia, lipid profile, electrocardiogram (EKG), and chest X-ray.</p></list-item>
<list-item>
<p>Natriuretic peptides (NPs): have a consolidated role in HF diagnosis. In patients with atrial fibrillation, serum values can rise 3 to 3.5 times, but in obese patients, this may significantly decrease. The following are accepted cutoff points: B-type natriuretic peptide (BNP) &#x2264; 35 pg/mL and/or N-terminal-pro-BNP (NT-proBNP) &#x2264; 125 pg/mL make a diagnosis of HFpEF less likely.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref></p></list-item>
<list-item>
<p>Noninvasive cardiac tests: EKG, echocardiography (ECHO) to estimate LVEF and, in case of suspected myocardial ischemia, provocative tests as the treadmill test.</p></list-item>
<list-item>
<p>Functional capacity tests: the 6-minute walk test, cardiopulmonary tests, and spirometry offer practical information on functional capacity. Ergospirometry-derived indices are the gold standards on functional capacity but are rarely available outside high complexity health units.</p></list-item></list>
<p>In this step, if the clinical, biomarkers and echocardiographic indices are unmistakably altered, HFpEF should be confirmed; however, a normal resting EKG and normal serum levels of NPs make the diagnosis of HFpEF less likely, although normal levels of NPs do not exclude HFpEF.</p>
</sec>
<sec>
<title>Step 2 - Confirmatory scores</title>
<p>If there is still doubt on the diagnosis of the syndrome, the next proposal is to confirm it with scoring. The H<sub>2</sub>FPEF and HFA-PEFF have recently been developed to establish the probable diagnosis of HFpEF.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref> They were validated in retrospective cohorts and demonstrated a higher diagnostic accuracy.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B7"><sup>7</sup></xref> These scores are offered in parallel, depending on their availability. The H<sub>2</sub>FPEF score was derived from clinical and echocardiographic variables that were independently associated with the invasive diagnosis of HFpEF in a population-based cohort. Each criterion generate a score that will estimate the probability of diagnosing the syndrome (<xref ref-type="fig" rid="f2">Figure 2</xref>).</p>
<fig id="f2">
<label>Figure 2</label>
<caption>
<title>H<sub>2</sub>FPEF score. BMI: body mass index; PASP: pulmonary artery systolic pressure; ECHO: echocardiography; E/e&#x2019;: left ventricular filling pressure non-invasive index</title>
<p>Ref. Reddy YNV, Carter RE, Obokata M, Redfield MM, Borlaug BA. A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction. Circulation. 2018;138(9):861-870.</p></caption>
<graphic xlink:href="0000-0000-abchf-001-01-0063-gf02.tif"/></fig>
<p>The other available score, HFA-PEFF, is composed of morphological and functional parameters, derived from a comprehensive ECHO, along with serum levels of NPs. A model of major and minor criteria is used to score and estimate the diagnostic probability (<xref ref-type="fig" rid="f3">Figure 3</xref>).</p>
<fig id="f3">
<label>Figure 3</label>
<caption>
<title>HFA-PEFF score. TRV: tricuspid valve regurgitation velocity; PASP: pulmonary artery systolic pressure; LAVI: left atrial volume; LVMI: left ventricular mass index; M: men / W: women; RWT: relative wall thickness; BNP: B-type natriuretic peptide; NT-proBNP: N-terminal pro&#x2013;B-type natriuretic peptide; GLS: global longitudinal strain; e&#x2019;: early diatolic myocardial velocity.</title>
<p>Ref. Pieske B, Tsch&#xF6;pe C, de Boer RA, et al. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur J Heart Fail. 2020;22(3):391-412.</p></caption>
<graphic xlink:href="0000-0000-abchf-001-01-0063-gf03.tif"/></fig>
<p>In this strategy, using any of two scores, HFpEF can be ruled out in patients with low scores (0 or 1) and confirmed with higher scores (H<sub>2</sub>FPEF &#x2265; 6 or HFA-PEFF &#x2265; 5). Conversely, in patients with intermediate scores (H<sub>2</sub>FPEF 2-5 or HFA-PEFF 2-4), an invasive or either a non-invasive hemodynamic exercise test is necessary (<xref ref-type="fig" rid="f1">Figure 1</xref>).</p>
</sec>
<sec>
<title>Step 3: Diastolic stress test or invasive investigation</title>
<p>A diastolic stress test should be added to the preceding approach of HFpEF if measurements of diastolic function are inconclusive at rest, like when H<sub>2</sub>FPEF score sums 2-5 points and HFA-PEFF score sums 2-4 points, respectively. Stress ECHO (SE) is capable of studying diastole, along with systolic function based on E/e&#x2019; ratio, which estimates the LV filling pressure plus the tricuspid valve regurgitation velocity (TRV), thus allowing for the estimation of the pulmonary artery systolic pressure.</p>
<p>According to the HFA-PEFF consensus,<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> an additional score is added to the one of step 2 (2 points if E/e&#xB4; ratio &#x2265; 15;, 3 points if E/e&#xB4; ratio &#x2265; 15 and TRV &#x3E; 3.4 m/s). If the final sum is &#x2265; 5, diagnostic criteria for HFpEF are reached. Diastolic SE is positive for diagnosing if the average peak E/e&#xB4; ratio is &#x2265; 15, with or without a peak TRV &#x2265; 3.4 m/s.</p>
<p>If diastolic SE does not provide confirmation, an invasive measurement of pulmonary capillary wedge pressure at rest or during SE is indicated. Invasive strategy, although more expensive and less available, is still the gold standard diagnostic method.</p>
</sec>
</sec>
<sec>
<title>Etiological investigation</title>
<p>Once the diagnosis is confirmed, focus should be directed to the systematic search for etiology, which can be divided into primary and secondary.<xref ref-type="bibr" rid="B6"><sup>6</sup></xref> The primary form combines common metabolic and hemodynamic characteristics, such as obesity, diabetes, and hypertension. The secondary form, which is less common, has specific etiologies such as ischemic, infiltrative, restrictive, inflammatory, infectious, toxic, or genetic, and should be actively sought. Mimics of HFpEF have diagnostic clues to aid early identification of phenocopies comprising constrictive pericarditis, primary valvular heart disease, or high-output syndrome, which should not be considered as the HFpEF syndrome, since the latter can determine different clinical outcomes; therefore, a definitive diagnosis is necessary. The big challenge is to adapt the diagnostic strategy for each health system, without unfocusing on the best practice of evidence-based medicine.</p>
</sec></body>
<back>
<fn-group>
<fn fn-type="other" id="fn1">
<p><bold>Ethics approval and consent to participate</bold></p>
<p>This article does not contain any studies with human participants or animals performed by any of the authors.</p></fn>
<fn fn-type="supported-by" id="fn2">
<p><bold>Sources of Funding</bold></p>
<p>There were no external funding sources for this study.</p></fn>
<fn fn-type="other" id="fn3">
<p><bold>Study Association</bold></p>
<p>This study is not associated with any thesis or dissertation work.</p></fn></fn-group>
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<article-title>Emerging Topics in Heart Failure: Heart Failure With Preserved and Mid-Range Ejection Fraction</article-title>
<source>Arq Bras Cardiol</source>
<year>2020</year>
<month>11</month>
<volume>115</volume>
<issue>5</issue>
<fpage>949</fpage>
<lpage>952</lpage></element-citation>
<mixed-citation>6. Silva MM, Rocha R, Brito FS, Jorge AJ, Issa VS, Danzmann LC. Emerging Topics in Heart Failure: Heart Failure With Preserved and Mid-Range Ejection Fraction. Arq Bras Cardiol. 2020 Nov;115(5):949-52.</mixed-citation></ref>
<ref id="B7">
<label>7</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name><surname>Aizpurua</surname><given-names>AB</given-names></name>
<name><surname>Wijk</surname><given-names>SS</given-names></name>
<name><surname>Rocca</surname><given-names>HP</given-names></name>
<name><surname>Henkens</surname><given-names>M</given-names></name>
<name><surname>Heymans</surname><given-names>S</given-names></name>
<name><surname>Nelson</surname><given-names>L</given-names></name>
<etal/></person-group>
<article-title>Validation of the HFA-PEFF score for the diagnosis of heart failure with preserved ejection fraction</article-title>
<source>Eur J Heart Fail</source>
<year>2020</year>
<month>03</month>
<volume>22</volume>
<issue>3</issue>
<fpage>413</fpage>
<lpage>421</lpage></element-citation>
<mixed-citation>7. Aizpurua AB, Wijk SS, Rocca HP, Henkens M, Heymans S, Nelson L, et al. Validation of the HFA-PEFF score for the diagnosis of heart failure with preserved ejection fraction. Eur J Heart Fail. 2020 Mar;22(3):413-21.</mixed-citation></ref></ref-list>
</back>
<sub-article article-type="translation" id="S01" xml:lang="pt">
<front-stub>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Comunica&#xE7;&#xE3;o Breve</subject></subj-group></article-categories>
<title-group>
<article-title>O Desafio do Diagn&#xF3;stico da ICFEp no Brasil</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-5774-2780</contrib-id>
<name><surname>Danzmann</surname><given-names>Luiz Cl&#xE1;udio</given-names></name><xref ref-type="aff" rid="aff7"><sup>1</sup></xref><xref ref-type="aff" rid="aff8"><sup>2</sup></xref> <xref ref-type="corresp" rid="c2"/></contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0001-9940-0829</contrib-id>
<name><surname>Belyavskiy</surname><given-names>Evgeny</given-names></name><xref ref-type="aff" rid="aff9"><sup>3</sup></xref><xref ref-type="aff" rid="aff10"><sup>4</sup></xref></contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0003-0034-4981</contrib-id>
<name><surname>Jorge</surname><given-names>Ant&#xF4;nio Jos&#xE9; Lagoeiro</given-names></name><xref ref-type="aff" rid="aff11"><sup>5</sup></xref></contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-7452-3870</contrib-id>
<name><surname>Mesquita</surname><given-names>Evandro Tinoco</given-names></name><xref ref-type="aff" rid="aff11"><sup>5</sup></xref></contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-5357-9138</contrib-id>
<name><surname>Torres</surname><given-names>Marco Antonio Rodrigues</given-names></name><xref ref-type="aff" rid="aff12"><sup>6</sup></xref></contrib>
<aff id="aff7">
<label>1</label>
<addr-line>
<named-content content-type="city">Canoas</named-content>
<named-content content-type="state">RS</named-content></addr-line>
<country country="BR">Brasil</country>
<institution content-type="original">Universidade Luterana do Brasil (ULBRA), Canoas, RS - Brasil</institution></aff>
<aff id="aff8">
<label>2</label>
<addr-line>
<named-content content-type="city">Porto Alegre</named-content>
<named-content content-type="state">RS</named-content></addr-line>
<country country="BR">Brasil</country>
<institution content-type="original">Hospital S&#xE3;o Lucas da PUC-RS, Porto Alegre, RS - Brasil</institution></aff>
<aff id="aff9">
<label>3</label>
<country country="DE">Alemanha</country>
<institution content-type="original">Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum Charit&#xE9;, Universit&#xE4;tsmedizin Berlin - Alemanha</institution></aff>
<aff id="aff10">
<label>4</label>
<country country="DE">Alemanha</country>
<institution content-type="original">German Center for Cardiovascular Research (DZHK), partner site Berlin - Alemanha</institution></aff>
<aff id="aff11">
<label>5</label>
<addr-line>
<named-content content-type="city">Niter&#xF3;i</named-content>
<named-content content-type="state">RJ</named-content></addr-line>
<country country="BR">Brasil</country>
<institution content-type="original">Universidade Federal Fluminense (UFF), Niter&#xF3;i, RJ - Brasil</institution></aff>
<aff id="aff12">
<label>6</label>
<addr-line>
<named-content content-type="city">Porto Alegre</named-content>
<named-content content-type="state">RS</named-content></addr-line>
<country country="BR">Brasil</country>
<institution content-type="original">Programa de P&#xF3;s-Gradua&#xE7;&#xE3;o em Ci&#xEA;ncias Pneumol&#xF3;gicas da Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS - Brasil</institution></aff></contrib-group>
<author-notes>
<corresp id="c2"><bold>Correspond&#xEA;ncia: Luiz Claudio Danzmann</bold> &#x2022; Rua Visconde do Herval, 472/903. CEP <postal-code>90130-150</postal-code>, Porto Alegre, RS &#x2013; Brasil. E-mail: <email>luiz.danzmann@ulbra.br</email></corresp>
<fn fn-type="conflict">
<p><bold>Potencial conflito de interesse</bold></p>
<p>N&#xE3;o h&#xE1; conflito com o presente artigo</p></fn>
<fn fn-type="con">
<p><bold>Contribui&#xE7;&#xE3;o dos autores</bold></p>
<p>Concep&#xE7;&#xE3;o e desenho da pesquisa, Reda&#xE7;&#xE3;o do manuscrito e Revis&#xE3;o cr&#xED;tica do manuscrito quanto ao conte&#xFA;do intelectual importante: Danzmann LC, Belyavskiy E, Jorge AJL, Mesquita ET, Torres MAR; Obten&#xE7;&#xE3;o de dados e An&#xE1;lise e interpreta&#xE7;&#xE3;o dos dados: Danzmann LC, Jorge AJL, Mesquita ET; An&#xE1;lise estat&#xED;stica e Obten&#xE7;&#xE3;o de financiamento: Danzmann LC.</p></fn></author-notes>
<abstract>
<title>Resumo</title>
<p>A insufici&#xEA;ncia card&#xED;aca com fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o preservada (ICFEp) &#xE9; altamente prevalente no Brasil e em todo o mundo. Entretanto, os crit&#xE9;rios diagn&#xF3;sticos recente s&#xE3;o complexos e de dif&#xED;cil aplica&#xE7;&#xE3;o no sistema de sa&#xFA;de brasileiro. Esta revis&#xE3;o prop&#xF5;e a adapta&#xE7;&#xE3;o dos crit&#xE9;rios diagn&#xF3;sticos modernos para as necessidades de cada paciente, da aten&#xE7;&#xE3;o prim&#xE1;ria &#xE0; mais complexa, utilizando um sistema de tr&#xEA;s etapas de complexidade e salientando a import&#xE2;ncia da investiga&#xE7;&#xE3;o da etiologia espec&#xED;fica da doen&#xE7;a.</p></abstract>
<kwd-group xml:lang="pt">
<title>Palavras-chave</title>
<kwd>Insufici&#xEA;ncia Card&#xED;aca/fisiopatologia</kwd>
<kwd>Volume Sist&#xF3;lico</kwd>
<kwd>Diagn&#xF3;stico por Imagem</kwd>
<kwd>Dispneia</kwd>
<kwd>Ecocardiografia/m&#xE9;todos</kwd>
<kwd>Fadiga</kwd>
<kwd>Rigidez Vascular</kwd>
<kwd>Comorbidades</kwd></kwd-group></front-stub>
<body>
<p>A insufici&#xEA;ncia card&#xED;aca com fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o preservada (ICFEp) ainda &#xE9; um grande problema de sa&#xFA;de p&#xFA;blica em todo o mundo e tamb&#xE9;m no Brasil.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> O reconhecimento e o diagn&#xF3;stico dessa s&#xED;ndrome continuam sendo um desafio, devido &#xE0; sua complexidade fisiopatol&#xF3;gica e &#xE0; sua diversidade fenot&#xED;pica.</p>
<p>As evid&#xEA;ncias cient&#xED;ficas atuais sobre a etiopatog&#xEA;nese forneceram recomenda&#xE7;&#xF5;es diagn&#xF3;sticas mais precisas, mas requerem avalia&#xE7;&#xF5;es ecocardiogr&#xE1;ficas abrangentes.<xref ref-type="bibr" rid="B2"><sup>2</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B3"><sup>3</sup></xref> Uma recomenda&#xE7;&#xE3;o recentemente publicada pela Associa&#xE7;&#xE3;o de Insufici&#xEA;ncia Card&#xED;aca da Sociedade Europeia de Cardiologia (<italic>Heart Failure Association of the European Society of Cardiology</italic>, HFA-ESC) trouxe um panorama abrangente e um algoritmo para o diagn&#xF3;stico da ICFEp.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref></p>
<sec>
<title>Existem quatro elementos b&#xE1;sicos para o diagn&#xF3;stico da ICFEp:</title>
<list list-type="order">
<list-item>
<p>Reconhecimento dos sinais e sintomas t&#xED;picos (por exemplo, dispneia, fadiga, diminui&#xE7;&#xE3;o da toler&#xE2;ncia ao exerc&#xED;cio e sinais de congest&#xE3;o) e comorbididades relacionadas &#xE0; IC;<xref ref-type="bibr" rid="B5"><sup>5</sup></xref></p></list-item>
<list-item>
<p>Fun&#xE7;&#xE3;o do ventr&#xED;culo esquerdo (VE) preservada, isto &#xE9;, fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o do VE (FEVE) &#x2265; 50%;</p></list-item>
<list-item>
<p>Remodelamento do &#xE1;trio esquerdo e do VE;</p></list-item>
<list-item>
<p>Evid&#xEA;ncia direta ou indireta de press&#xE3;o de enchimento do VE elevada.</p></list-item></list>
</sec>
<sec>
<title>Diagn&#xF3;stico baseado em tr&#xEA;s etapas</title>
<p>Em um artigo recentemente publicado,<xref ref-type="bibr" rid="B6"><sup>6</sup></xref> prop&#xF4;s uma compila&#xE7;&#xE3;o dos crit&#xE9;rios das Diretrizes da Sociedade Brasileira de Cardiologia (SBC), da Cl&#xED;nica Mayo e da HFA-ESC adaptados para o sistema de sa&#xFA;de nacional. Recomenda-se uma abordagem em tr&#xEA;s n&#xED;veis de complexidade, adaptando-se o uso de recursos desde a aten&#xE7;&#xE3;o prim&#xE1;ria (etapa 1) at&#xE9; os centros de sa&#xFA;de de alta complexidade (etapas 2 e 3) (<xref ref-type="fig" rid="f4">Figura 1</xref>).</p>
<fig id="f4">
<label>Figura 1</label>
<caption>
<title>Algoritmo diagn&#xF3;stico para ICFEp. IC: insufici&#xEA;ncia card&#xED;aca; FEVE = fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o do ventr&#xED;culo esquerdo.</title></caption>
<graphic xlink:href="0000-0000-abchf-001-01-0063-gf01-pt.tif"/></fig>
<sec>
<title>Etapa 1: Abordagem cl&#xED;nica pr&#xE9;-teste</title>
<list list-type="bullet">
<list-item>
<p>Anamnese: identifica&#xE7;&#xE3;o de sinais e sintomas que offer a possibilidade de IC;</p></list-item>
<list-item>
<p>Comorbidades: diagn&#xF3;stico de caracter&#xED;sticas cl&#xED;nicas e morbidades importantes associadas ao risco de ICFEp, tais como idade &#x3E; 60 anos, sexo feminino, obesidade, hipertens&#xE3;o, diabetes, doen&#xE7;a card&#xED;aca isqu&#xEA;mica e fibrila&#xE7;&#xE3;o atrial.</p></list-item>
<list-item>
<p>Comorbidades agonistas ou concorrentes da IC: agonistas &#xE0; diminui&#xE7;&#xE3;o da capidade funcional, ou que representam diagn&#xF3;sticos diferenciais, tais como anemia, doen&#xE7;a pulmonar obstrutiva cr&#xF4;nica, asma, fibrose pulmonar, doen&#xE7;a arterial perif&#xE9;rica, sarcopenia, doen&#xE7;as da tireoide, nefropatias e desequil&#xED;brio eletrol&#xED;tico.</p></list-item>
<list-item>
<p>Testes b&#xE1;sicos: hemograma, creatinina, ureia, glicemia, perfil lip&#xED;dico, eletrocardiograma (ECG) e radiografia do t&#xF3;rax.</p></list-item>
<list-item>
<p>Pept&#xED;deos natriur&#xE9;ticos (<italic>natriuretic peptides</italic>, NPs): t&#xEA;m um papel consolidado no diagn&#xF3;stico da IC. Em pacientes com fibrila&#xE7;&#xE3;o atrial, os valores s&#xE9;ricos dos NP podem aumentar de 3 a 3,5 vezes, mas, em pacientes obesos, esses valores podem apresentar uma diminui&#xE7;&#xE3;o significativa. S&#xE3;o aceitos os seguintes pontos de corte: pept&#xED;deo natriur&#xE9;tico do tipo B (<italic>B-type natriuretic peptide</italic>, BNP) &#x2264; 35 pg/mL e/ou N-terminal-pro-BNP (NT-proBNP) &#x2264; 125 pg/mL tornam o diagn&#xF3;stico de ICFEp menos prov&#xE1;vel.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref></p></list-item>
<list-item>
<p>Testes card&#xED;acos n&#xE3;o invasivos: ECG, ecocardiograma (ECO) para estimar a FEVE e, em caso de suspeita de isquemia mioc&#xE1;rdica, testes provocativos como o teste de esteira.</p></list-item>
<list-item>
<p>Testes de capacidade funcional: o teste de caminhada de 6 minutos, testes cardiopulmonares, e espirometria oferecem informa&#xE7;&#xF5;es pr&#xE1;ticas sobre a capacidade funcional. Indicadores ergoespirom&#xE9;tricos s&#xE3;o o padr&#xE3;o ouro para a capacidade funcional, mas raramente est&#xE3;o dispon&#xED;veis foram de unidades de sa&#xFA;de de alta complexidade.</p></list-item></list>
<p>Nessa etapa, se os &#xED;ndices cl&#xED;nicos, os biomarcadores e os achados ecocardiogr&#xE1;ficos estiverem claramente alterados, deve-se confirmar a ICFEp; entretanto, ECG de repouso normal e n&#xED;veis s&#xE9;ricos de NPs normais tornam o diagn&#xF3;stico de ICFEp menos prov&#xE1;vel, embora n&#xED;veis normais de NPs n&#xE3;o excluam ICFEp.</p>
</sec>
<sec>
<title>Etapa 2 - Pontua&#xE7;&#xF5;es confirmat&#xF3;rias.</title>
<p>Se ainda houver d&#xFA;vida sobre o diagn&#xF3;stico da s&#xED;ndrome, a pr&#xF3;xima proposta &#xE9; confirm&#xE1;-lo com sistemas de pontua&#xE7;&#xE3;o. Os escores H<sub>2</sub>FPEF e HFA-PEFF foram recentemente elaborados para estabelecer o prov&#xE1;vel diagn&#xF3;stico de ICFEp.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref> Eles foram validados em coortes retrospectivas e demonstraram uma elevada precis&#xE3;o diagn&#xF3;stica.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B7"><sup>7</sup></xref> Esses escores s&#xE3;o oferecidos em paralelo, dependendo da sua disponibilidade. O escore H<sub>2</sub>FPEF foi derivado de vari&#xE1;veis cl&#xED;nicas e ecocardiogr&#xE1;ficas independentemente associadas ao diagn&#xF3;stico invasivo de ICFEp em uma coorte populacional. Cada crit&#xE9;rio gera uma pontua&#xE7;&#xE3;o que estimar&#xE1; a probabilidade de diagn&#xF3;stico da s&#xED;ndrome (<xref ref-type="fig" rid="f5">Figura 2</xref>).</p>
<fig id="f5">
<label>Figura 2</label>
<caption>
<title>Escore H<sub>2</sub>FPEF. IMC: &#xED;ndice de massa corporal; PSAP: press&#xE3;o sist&#xF3;lica da art&#xE9;ria pulmonar; ECO: ecocardiograma; E/e&#x2019;: &#xED;ndice de estimativa da press&#xE3;o de enchimento do ventr&#xED;culo esquerdo.</title>
<p>Ref. Reddy YNV, Carter RE, Obokata M, Redfield MM, Borlaug BA. A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction. Circulation. 2018;138(9):861-870.</p></caption>
<graphic xlink:href="0000-0000-abchf-001-01-0063-gf02-pt.tif"/></fig>
<p>O outro escore dispon&#xED;vel, o HFA-PEFF, &#xE9; composto por par&#xE2;metros morfol&#xF3;gicos e funcionais, derivados de ECO abrangente, al&#xE9;m de n&#xED;veis s&#xE9;ricos de NPs. Um modelo com crit&#xE9;rios maiores e menores &#xE9; utilizado para pontuar e estimar a probabilidade diagn&#xF3;stica (<xref ref-type="fig" rid="f6">Figura 3</xref>).</p>
<fig id="f6">
<label>Figura 3</label>
<caption>
<title>Escore HFA-PEFF. VRT: velocidade de regurgita&#xE7;&#xE3;o da valva tric&#xFA;spide; PSAP: press&#xE3;o sist&#xF3;lica da art&#xE9;ria pulmonar; IVAE: &#xED;ndice do volume do &#xE1;trio esquerdo; IMVE: &#xED;ndice da massa do ventr&#xED;culo esquerdo; H: homens / M: mulheres; ERP: espessura relativa da parede; BNP: pept&#xED;deo natriur&#xE9;tico do tipo B (B-type natriuretic peptide); NT-proBNP: N-terminal pro-BNP; GLS: tens&#xE3;o longitudinal global (global longitudinal strain); e&#x2019;: velocidade de deslocamento diast&#xF3;lica precoce.</title>
<p>Ref. Pieske B, Tsch&#xF6;pe C, de Boer RA, et al. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur J Heart Fail. 2020;22(3):391-412.</p></caption>
<graphic xlink:href="0000-0000-abchf-001-01-0063-gf03-pt.tif"/></fig>
<p>Nessa estrat&#xE9;gia, utilizando qualquer um dos dois escores, ICFEp pode ser descartada em pacientes com escores baixos (0 ou 1) e confirmada com escores elevados (H<sub>2</sub>FPEF &#x2265; 6 ou HFA-PEFF &#x2265; 5). Por outro lado, em pacientes com escores intermedi&#xE1;rios (H<sub>2</sub>FPEF 2-5 ou HFA-PEFF 2-4), &#xE9; necess&#xE1;ria a realiza&#xE7;&#xE3;o de um teste invasivo ou de um teste de exerc&#xED;cio hemodin&#xE2;mico (<xref ref-type="fig" rid="f4">Figura 1</xref>).</p>
</sec>
<sec>
<title>Etapa 3: Teste diast&#xF3;lico de esfor&#xE7;o ou investiga&#xE7;&#xE3;o invasiva</title>
<p>Deve-se acrescentar o teste de esfor&#xE7;o diast&#xF3;lico &#xE0; abordagem precedente da ICFEp se as medi&#xE7;&#xF5;es da fun&#xE7;&#xE3;o diast&#xF3;lica em repouso forem inconclusivas, como quando o escore H<sub>2</sub>FPEF somar 2-5 pontos e o escore HFA-PEFF somar 2-4 pontos, respectivamente. O ECO de esfor&#xE7;o &#xE9; capaz de analisar a di&#xE1;stole, al&#xE9;m da fun&#xE7;&#xE3;o sist&#xF3;lica, com base na raz&#xE3;o E/e&#x2019;, que estima a press&#xE3;o de enchimento do VE mais a velocidade de regurgita&#xE7;&#xE3;o da valva tric&#xFA;spide (VRT), permitindo assim estimar a press&#xE3;o sist&#xF3;lica da art&#xE9;ria pulmonar.</p>
<p>De acordo com o consenso da HFA-PEFF,<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> acrescenta-se uma pontua&#xE7;&#xE3;o adicional &#xE0;quela obtida na etapa 2 (2 pontos se a raz&#xE3;o E/e&#xB4; for &#x2265; 15; 3 pontos se a raz&#xE3;o E/e&#xB4; for &#x2265; 15 e a VR T &#x3E; 3,4 m/s). Se a soma final for &#x2265; 5, atende-se aos crit&#xE9;rios de diagn&#xF3;stico para ICFEp. O ECO diast&#xF3;lico de esfor&#xE7;o &#xE9; positivo para o diagn&#xF3;stico se o pico da raz&#xE3;o E/e&#xB4; for &#x2265; 15, com ou sem pico de VRT &#x2265; 3,4 m/s.</p>
<p>Se o ECO diast&#xF3;lico de esfor&#xE7;o n&#xE3;o fornecer a confirma&#xE7;&#xE3;o, &#xE9; indicada a mensura&#xE7;&#xE3;o invasiva da press&#xE3;o propulsora capilar pulmonar em repouso ou durante ECO de esfor&#xE7;o. A estrat&#xE9;gia invasiva, embora mais onerosa e menos dispon&#xED;vel, ainda &#xE9; o padr&#xE3;o ouro para o diagn&#xF3;stico.</p>
</sec>
</sec>
<sec>
<title>Investiga&#xE7;&#xE3;o etiol&#xF3;gica</title>
<p>Uma vez confirmado o diagn&#xF3;stico, deve-se focar a investiga&#xE7;&#xE3;o sistem&#xE1;tica da etiologia, a qual pode ser dividida em prim&#xE1;ria e secund&#xE1;ria.<xref ref-type="bibr" rid="B6"><sup>6</sup></xref> A forma prim&#xE1;ria combina caracter&#xED;sticas metab&#xF3;licas e hemodin&#xE2;micas comuns, tais como obesidade, diabetes e hipertens&#xE3;o. A segunda, que &#xE9; menos comum, apresenta etiologias espec&#xED;ficas, tais como isqu&#xEA;micas, infiltrativas, restritivas, inflamat&#xF3;rias, infecciosas, t&#xF3;xicas ou gen&#xE9;ticas, e deve ser investigada ativamente. Condi&#xE7;&#xF5;es que mimetizam a ICFEp apresentam ind&#xED;cios diagn&#xF3;sticos que auxiliam na identifica&#xE7;&#xE3;o precoce de fenoc&#xF3;pias, incluindo pericardite constritiva, cardiopatia valvular prim&#xE1;ria ou s&#xED;ndrome de alto d&#xE9;bito, as quais n&#xE3;o podem ser consideradas como a s&#xED;ndrome da ICFEp, pois esta pode determinar diferentes desfechos cl&#xED;nicos; portanto, um diagn&#xF3;stico definitivo &#xE9; necess&#xE1;rio. O maior desafio &#xE9; adaptar a estrat&#xE9;gia diagn&#xF3;stica para cada sistema de sa&#xFA;de sem tirar o foco das melhores pr&#xE1;ticas da medicina baseada em evid&#xEA;ncias.</p>
</sec></body>
<back>
<fn-group>
<fn fn-type="other" id="fn4">
<p><bold>Aprova&#xE7;&#xE3;o &#xE9;tica e consentimento informado</bold></p>
<p>Este artigo n&#xE3;o cont&#xE9;m estudos com humanos ou animais realizados por nenhum dos autores.</p></fn>
<fn fn-type="supported-by" id="fn5">
<p><bold>Fontes de financiamento</bold></p>
<p>O presente estudo n&#xE3;o teve fontes de financiamento externas.</p></fn>
<fn fn-type="other" id="fn6">
<p><bold>Vincula&#xE7;&#xE3;o acad&#xEA;mica</bold></p>
<p>N&#xE3;o h&#xE1; vincula&#xE7;&#xE3;o deste estudo a programas de p&#xF3;s-gradua&#xE7;&#xE3;o.</p></fn></fn-group>
</back></sub-article>
</article>
