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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">2764-3107</issn>
<publisher>
<publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name></publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">abc.20220059</article-id>
<article-id pub-id-type="doi">10.36660/abc.20220059</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Invasive Hemodynamic Monitoring in the Diagnosis of Heart Failure with Preserved Ejection Fraction</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-2178-1518</contrib-id>
<name><surname>Almeida</surname><given-names>Dirceu Rodrigues</given-names></name>
<role>Conception and design of the research</role>
<role>Acquisition of data</role>
<role>Analysis and interpretation of the data</role>
<role>Statistical analysis</role>
<role>Obtaining financing</role>
<role>Writing of the manuscript</role>
<role>Critical revision of the manuscript for important intellectual content</role>
<xref ref-type="aff" rid="aff1"/><xref ref-type="corresp" rid="c1"/>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-2612-8040</contrib-id>
<name><surname>Andrade</surname><given-names>Fernanda Almeida</given-names></name>
<role>Conception and design of the research</role>
<role>Acquisition of data</role>
<role>Analysis and interpretation of the data</role>
<role>Statistical analysis</role>
<role>Obtaining financing</role>
<role>Writing of the manuscript</role>
<role>Critical revision of the manuscript for important intellectual content</role>
<xref ref-type="aff" rid="aff1"/>
</contrib>
<aff id="aff1">
<label>1</label>
<institution content-type="orgname">Universidade Federal de S&#xE3;o Paulo</institution>
<addr-line>
<named-content content-type="city">S&#xE3;o Paulo</named-content>
<named-content content-type="state">SP</named-content>
</addr-line>
<country country="BR">Brazil</country>
<institution content-type="original">Universidade Federal de S&#xE3;o Paulo (UNIFESP) S&#xE3;o Paulo, SP &#x2013; Brazil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c1"><bold>Mailing Address: Dirceu Rodrigues Almeida</bold> &#x2022; Universidade Federal de S&#xE3;o Paulo &#x2013; Rua Botucatu, 830. Postal Code <postal-code>04021-001</postal-code>, S&#xE3;o Paulo, SP &#x2013; Brazil. E-mail: <email>dirceualmeida.unifesp@gmail.com</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>
</author-notes>
<pub-date publication-format="electronic" date-type="pub">
<day>01</day>
<month>12</month>
<year>2022</year></pub-date>
<pub-date publication-format="electronic" date-type="collection">
<season>Jul-Sep</season>
<year>2022</year></pub-date>
<volume>2</volume>
<issue>3</issue>
<fpage>290</fpage>
<lpage>295</lpage>
<history>
<date date-type="received">
<day>22</day>
<month>08</month>
<year>2022</year></date>
<date date-type="rev-recd">
<day>13</day>
<month>09</month>
<year>2022</year></date>
<date date-type="accepted">
<day>13</day>
<month>09</month>
<year>2022</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>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>Heart Failure</kwd>
<kwd>Heart Failure, Diastolic</kwd>
<kwd>Diagnosis</kwd>
</kwd-group>
<counts>
<fig-count count="6"/>
<table-count count="6"/>
<equation-count count="0"/>
<ref-count count="36"/>
<page-count count="6"/></counts></article-meta></front>
<body>
<sec sec-type="intro">
<title>Introduction</title>
<p>Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome that has a negative impact on quality of life and life expectancy of patients, with high hospitalization and mortality rates. HFpEF is a highly prevalent disease, probably due to the increase in the prevalence of common risk factors, such as advanced age, female sex, arterial hypertension, diabetes, renal failure and obesity.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup> It is estimated that nearly half of heart failure patients have preserved ejection fraction, defined as a left ventricular (LV) ejection fraction (LVEF) &#x2265;50%. Despite the publication of numerous original articles, reviews, books and guidelines, there are still doubts and controversies regarding the real incidence, etiopathogenesis, pathophysiology, prognosis, and mainly the difficulties in the correct diagnosis of HFpEF by non-invasive methods. In this paper, we will describe the importance of the invasive hemodynamic monitoring (IHM) for the correct diagnosis of HFpEF.<sup><xref ref-type="bibr" rid="B1">1</xref>&#x2013;<xref ref-type="bibr" rid="B4">4</xref></sup></p>
<sec>
<title>Non-invasive diagnosis of heart failure with preserved ejection fraction</title>
<p>Before addressing the role of IHM in the diagnosis of HFpEF, we will briefly consider the non-invasive methods available for this purpose and highlight their main limitations.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
<p>Because of the difficulty or even impossibility of a clinical differential diagnosis between HFpEF and heart failure with reduced ejection fraction (HFrEF), all guidelines recommend the use of two-dimensional color Doppler for a detailed evaluation of diastolic function.<sup><xref ref-type="bibr" rid="B6">6</xref>&#x2013;<xref ref-type="bibr" rid="B9">9</xref></sup> In the assessment of diastolic function, we will analyze several echocardiographic parameters (mitral flow, tissue doppler, left atrial volume and area, pulmonary artery pressure), which, when combined, allow the diagnosis of HFpEF.<sup><xref ref-type="bibr" rid="B6">6</xref>&#x2013;<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B10">10</xref></sup></p>
<p>Analysis of mitral flow is the first step in the assessment of diastolic function in patients with sinus rhythm. By Doppler echocardiography, it is possible to determine the early wave (E wave) and the late wave (A wave) of LV filling.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> E wave represents the rapid filling by difference of pressure, and the A wave represents active filling by atrial contraction. Diastole is analyzed by the relationship between E and A waves together with the deceleration time of E wave. E wave velocity can be analyzed in conjunction with tissue Doppler as we will see below. In healthy subjects, the ratio between the velocities of the E and A waves &#x2013; the e/a ratio &#x2013; is greater 1.0. Aging is associated with stiffening of the left ventricle, leading to a decrease in E wave velocity and lower deceleration time of the wave, and an increase in A wave velocity resulting in a E/A ratio lower than 1.0. This pattern of filling is known as change of relaxation, which does not imply a pathology per se, and, in most patients, does not indicate an increase in filling pressure or in LV end-diastolic pressure.</p>
<p>In patients with a reduction in LV compliance and increased LV diastolic pressure, a rapid equalization of left atrial and LV pressures is observed, resulting in early interruption of blood flow. Consequently, there is an increase in E wave velocity and decrease in deceleration time, associated with a reduction in A wave velocity. With these changes, the LV filling pattern becomes similar to the normal pattern and named as pseudonormal pattern, which probably indicates the presence of pathological diastolic dysfunction. The differentiation between the pseudonormal and normal patterns can be made by the Valsalva maneuver, with the increase of diastolic and LV filling pressures. These mitral flow changes tend to become more pronounced, with an increase in the E/A ratio (to values greater than 2.0), greater reduction in the E wave deceleration time and A wave velocity, characterizing the restrictive pattern of LV filling, which also results in probable pathological diastolic dysfunction.<sup><xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B12">12</xref></sup> Notably, the analysis of the E/A ratio has important limitations in the diagnosis of HFpEF for depending on several variables, including heart rate, arrhythmia, preload (blood volume), and afterload (hypertension). Therefore, this analysis is only accurate in patients with sinus rhythm and normal heart rate.<sup><xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B11">11</xref></sup></p>
<p>Tissue Doppler echocardiography measures the velocity of basal myocardium displacement and mitral ring motion. Tissue Doppler curves are obtained from the apical four chamber view, in the septal and lateral mitral ring, where three wave velocities can be determined: early diastolic wave (e&#x2019;), end diastolic wave (a&#x2019;) and systolic wave (s). In case of altered relaxation, e wave velocity is reduced, regardless of LV filling pressures. The greatest importance of this method in the assessment of diastolic function is that it allows concomitant analysis of Doppler indices of mitral inflow, particularly mitral E wave and e&#x2019; wave (septal, lateral or medial) of tissue Doppler imaging. The E/e&#x2019; ratio has been used as an indirect measure of pulmonary capillary pressure or LV end diastolic pressure. Nevertheless, in HFpEF patients, the analysis of ventricular filling parameters, including the E/e&#x2019; ratio, compared with filling pressure measures obtained from simultaneous IHM has low, or at most, moderate predictive value in estimating filling pressure.<sup><xref ref-type="bibr" rid="B13">13</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup> E/e&#x2019; ratio has weak correlation with hemodynamic measures, especially when the ratio is below 15. It is worth mentioning that calculation of the E/e&#x2019; ratio depends on an adequate echocardiographic window and presence of sinus rhythm and is influenced by valvular changes such as mitral annular calcification and mitral insufficiency, both common in the elderly.<sup><xref ref-type="bibr" rid="B12">12</xref>&#x2013;<xref ref-type="bibr" rid="B14">14</xref></sup></p>
<p>All these echocardiographic parameters may not be altered at rest and in this case should be interpreted with caution. Most patients with HFpEF experience symptoms with activity only due to increases in filling pressure. Thus, the measurement of echocardiographic parameters, particularly the E/e&#x2019; ratio during exercise (diastolic stress test) is more sensitive and can be useful in the assessment of these patients. While the E/&#x27;e&#x27; ratio is not affected during exercise in healthy individuals, it increases in patients with LV diastolic function, with a correlation with filling pressure and pulmonary pressure increases. Therefore, diastolic stress test should be considered for patients with a HFpEF phenotype, clinical presentation of heart failure and E/e&#x2019; ration lower than 15.<sup><xref ref-type="bibr" rid="B13">13</xref>&#x2013;<xref ref-type="bibr" rid="B18">18</xref></sup> Performance of lung ultrasound concomitantly with diastolic stress test may help to detect pulmonary congestion with an elevation of pulmonary capillary pressure.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Limitations of stress echocardiography include its unavailability as a routine test in most echocardiography laboratory, poor echocardiographic window, dependence on operator experience in obtaining the hemodynamic parameters, and the fact that the quality of images is affected by tachypnea during exercise. Only 50% of patients undergoing stress echocardiography have adequate echocardiographic window. In addition, atrial fibrillation is a limiting factor that corroborates the poor accuracy of echocardiogram in assessing filling pressure during stress.<sup><xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B13">13</xref></sup></p>
<p>In light of limitations of invasive methods here described and the lack of consensus about the best way to diagnose HFpEF, some authors have tried to establish uniform criteria in this regard. Considering the difficulties in confirming the non-invasive diagnosis of HFpEF, diagnostic scores are important to strengthen a clinical suspicion and screen eligible patients for IHM.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup></p>
<p>The H2FPEF score is the most widely used scoring system (<xref ref-type="table" rid="t1">Table 1</xref>), as it can be easily and accurately calculated.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> The score was developed in a cohort of patients with unexplained dyspnea who were referred for right heart catheterization and stress test. The score includes six clinical and echocardiographic variables: age &#x3E;60 years, body mass index (BMI) &#x3E;30 kg/m<sup>2</sup>, arterial hypertension (treatment with &#x2265;2 antihypertensives), atrial fibrillation (permanent or paroxysmal), echocardiographic E/e&#x2019; ratio &#x3E;9 and echocardiographically derived systolic pulmonary artery pressure &#x3E;35 mmHg. The presence of atrial fibrillation yields 3 points, a BMI &#x3E; 30 kg/m<sup>2</sup> yields 2 points, and the other criteria yield 1 point. The H2FPEF had good discriminatory ability (area under the ROC curve of 0.84) and higher sensitivity and specificity to exclude or confirm HFpEF as compared with the HFA-PEFF score.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> Since the HFpEF score estimates disease likelihood, the instrument can be used to effectively rule out the disease among patients with low scores (0 or 1), and confirm the diagnosis of HF2pEF with reasonably certainty in patients with high scores (&#x3E;9). Therefore, the HF2pEF score should be used to identify patients with intermediate scores (2-9), who would require additional tests.<sup><xref ref-type="bibr" rid="B19">19</xref>,<xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B23">23</xref></sup></p>
<table-wrap id="t1">
<label>Table 1</label>
<caption><title>H2FPEF score for the diagnosis of heart failure with preserved ejection fraction</title></caption>
<table frame="hsides" rules="rows">
<colgroup width="20%">
<col/>
<col/>
<col/>
<col/>
</colgroup>
<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
<tr>
<th align="left" valign="middle"/>
<th align="left" valign="middle">Clinical variables</th>
<th align="center" valign="middle">Values</th>
<th align="center" valign="middle">Points</th>
</tr>
</thead>
<tbody style="border-bottom: thin solid; border-color: #000000">
<tr>
<td align="left" valign="middle" rowspan="2">H2</td>
<td align="center" valign="middle">Body weight (Heavy)</td>
<td align="center" valign="middle">BMI &#x3E; 30kg/m&#xB2;</td>
<td align="center" valign="middle">2</td>
</tr>
<tr>
<td align="left" valign="middle">Arterial hypertension</td>
<td align="center" valign="middle">&#x2265; anti-hypertensives</td>
<td align="center" valign="middle">1</td>
</tr>
<tr>
<td align="left" valign="middle">F</td>
<td align="center" valign="middle">Atrial fibrillation</td>
<td align="center" valign="middle">Paroxysmal or persistent</td>
<td align="center" valign="middle">3</td>
</tr>
<tr>
<td align="left" valign="middle">P</td>
<td align="center" valign="middle">Pulmonary hypertension</td>
<td align="center" valign="middle">PASP &#x2265;35mmHg</td>
<td align="center" valign="middle">1</td>
</tr>
<tr>
<td align="left" valign="middle">E</td>
<td align="center" valign="middle">Elder</td>
<td align="center" valign="middle">&#x3E; 60 anos</td>
<td align="center" valign="middle">1</td>
</tr>
<tr>
<td align="left" valign="middle">F</td>
<td align="center" valign="middle">Filling Pressure</td>
<td align="center" valign="middle">E/e&#xB4;&#x3E; 9</td>
<td align="center" valign="middle">1</td>
</tr>
</tbody>
</table>
<table frame="hsides" rules="rows">
<colgroup width="10%">
<col/>
<col/>
<col/>
<col/>
<col/>
<col/>
<col/>
<col/>
<col/>
<col/>
</colgroup>
<tbody style="border-bottom: thin solid; border-color: #000000">
<tr>
<td colspan="10" align="left" valign="middle"><bold>Total score</bold></td>
</tr>
<tr>
<td align="left" valign="middle">0</td>
<td align="left" valign="middle">1</td>
<td align="left" valign="middle">2</td>
<td align="left" valign="middle">3</td>
<td align="left" valign="middle">4</td>
<td align="left" valign="middle">5</td>
<td align="left" valign="middle">6</td>
<td align="left" valign="middle">7</td>
<td align="left" valign="middle">8</td>
<td align="left" valign="middle">9</td>
</tr>
<tr style="background-color:#ED1C24">
<td align="left" valign="middle">0.2</td>
<td align="left" valign="middle">0.3</td>
<td align="left" valign="middle">0.4</td>
<td align="left" valign="middle">0.5</td>
<td align="left" valign="middle">0.6</td>
<td align="left" valign="middle">0.7</td>
<td align="left" valign="middle">0.8</td>
<td align="left" valign="middle">0.9</td>
<td align="left" valign="middle">0.96</td>
<td align="left" valign="middle" />
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TFN1"><p>BMI: body mass index; PASP: pulmonary artery systolic pressure</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec>
<title>Likelihood of HFpEF</title>
<p>Diagnostic apps may be useful in clinical practice, as they are based on scores that provide information about diagnostic probability of HFpEF with acceptable sensitivity and specificity. Hence, patients with high probability of diagnosis are identified, as well as patients with intermediate probability are screened for more meaningful tests, like the IHM, which provides direct measurements of filling pressures (pulmonary capillary pressure and/or LV end diastolic pressure) and pulmonary arterial pressure at rest and during exercise.<sup><xref ref-type="bibr" rid="B21">21</xref></sup></p>
</sec>
<sec>
<title>IHM in HFpEF</title>
<p>Exertional dyspnea is a common condition in patients with cardiopulmonary diseases. To elucidate the etiology of dyspnea in clinical practice, we analyze epidemiological data and clinical history, and perform physical examination. Tests like spirometry, cardiopulmonary exercise test and imaging tests help in the diagnosis of diseases that affect the ventilatory function.<sup><xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B23">23</xref></sup> Echocardiography is always used in the cardiological assessment, but, unfortunately, is performed at resting conditions only. In addition, important limitations of the test are not usually considered, including a poor window (due to obesity, chest deformation, pulmonary hyperinflation), and especially atrial fibrillation, which hampers the analysis of diastolic function.<sup><xref ref-type="bibr" rid="B14">14</xref>&#x2013;<xref ref-type="bibr" rid="B16">16</xref></sup></p>
<p>The presence of HFpEF should always be considered to differentiate a pulmonary and cardiac cause of dyspnea, as it is responsible for 30-50% of the cases of dyspnea or pulmonary hypertension in patients undergoing IHM.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B23">23</xref>,<xref ref-type="bibr" rid="B24">24</xref></sup> IHM at rest and during exercise is the best method to elucidate the causes of exertional dyspnea and pulmonary hypertension. It is currently considered the gold standard for the diagnosis of HFpEF, allowing the direct measurement of ventricular filling pressure, pulmonary pressure, cardiac output, and pulmonary vascular resistance.<sup><xref ref-type="bibr" rid="B24">24</xref>&#x2013;<xref ref-type="bibr" rid="B26">26</xref></sup> In addition, the method is very useful in patients with mixed diseases, like heart failure and pulmonary disease, as it informs us whether the most limiting factor for exercise has a predominantly cardiac or pulmonary cause.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup></p>
<p>Current guidelines for the diagnosis of HFpEF highlight the limitations of echocardiographic data obtained at rest, due to its low sensitivity and low specificity, in addition to technical drawbacks in acquiring echocardiographic parameters for diastolic function assessment. Then, stress echocardiography has been recommended for the diagnosis of HFpEF, although several limitations still exist. Thus, the direct measurement of filling pressures at rest is the only instrument capable of excluding the diagnosis of HFpEF due to its high sensitivity (100%) and specificity (100%) values. Therefore, IHM at rest and during exercise is the only method able to confirm or refute the diagnosis of HFpEF.<sup><xref ref-type="bibr" rid="B22">22</xref>&#x2013;<xref ref-type="bibr" rid="B26">26</xref></sup></p>
<p>In addition to allowing an early diagnosis of HFpEF, the IHM provides important information about the severity and prognosis of HFpEF. Increased pulmonary capillary pressure during exercise and its relation to cardiac output are correlated with a worse prognosis in short and medium term.<sup><xref ref-type="bibr" rid="B27">27</xref>,<xref ref-type="bibr" rid="B28">28</xref></sup></p>
<p>Invasive hemodynamic assessment at rest is useful in cases of hemodynamic abnormalities such as elevations in filling pressures. However, in cases of normal filling pressure, which do not exclude the diagnosis of HFpEF, the method has limited sensitivity, since in this situation, a rise in filling pressure only occurs with exercise.<sup><xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup> Therefore, only IHM during exercise allows to confirm or to exclude HFpEF as the cause of dyspnea, with a sensitivity and specificity of 100%.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B23">23</xref></sup> Although alternatives like acute volume overload and leg raise to increase venous return may be of some help, they should not replace the hemodynamic monitoring with exercise; these alternative strategies should be reserved for patients who cannot carry out exercises involving lower limbs and for dehydrated patients at resting blood pressure time.<sup><xref ref-type="bibr" rid="B29">29</xref>,<xref ref-type="bibr" rid="B30">30</xref></sup></p>
</sec>
<sec>
<title>Indications for IHM in HFpEF</title>
<p>The management of all patients with HFpEF, elderly patients with unexplained pulmonary hypertension, and patients with unexplained dyspnea should be performed according to the flowcharts for HFpEF that include diagnostic scores and parameters for the assessment of diastolic function by echocardiography at rest or diastolic stress test.<sup><xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B23">23</xref></sup> In previous studies, approximately 50% of patients with an intermediate risk score who did not undergo IHM with exertion stress may have HFpEF.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup> The main indications for IHM are listed in <xref ref-type="table" rid="t2">Table 2</xref>.</p>
<table-wrap id="t2">
<label>Table 2</label>
<caption><title>Main indications for invasive hemodynamic monitoring</title></caption>
<table frame="hsides" rules="rows">
<colgroup width="50%">
<col/>
<col/>
</colgroup>
<tbody style="border-bottom: thin solid; border-color: #000000">
<tr>
<td align="left" valign="middle">1</td>
<td align="left" valign="middle">Patients with a poor echocardiographic window for the assessment of diastolic function by resting echocardiography</td>
</tr>
<tr>
<td align="left" valign="middle">2</td>
<td align="left" valign="middle">Impossibility of obtaining reliable parameters by stress echocardiography</td>
</tr>
<tr>
<td align="left" valign="middle">3</td>
<td align="left" valign="middle">Patients with permanent atrial fibrillation</td>
</tr>
<tr>
<td align="left" valign="middle">4</td>
<td align="left" valign="middle">Patients with an intermediate H2FPEF score (4-8 points)</td>
</tr>
<tr>
<td align="left" valign="middle">5</td>
<td align="left" valign="middle">Patients with an E/e&#xB4; ratio between entre 9 and 15</td>
</tr>
<tr>
<td align="left" valign="middle">6</td>
<td align="left" valign="middle">Patients with pulmonary disease or mixed disease like CPOD that may be the cause of dyspnea</td>
</tr>
<tr>
<td align="left" valign="middle">7</td>
<td align="left" valign="middle">Dyspnea and/or pulmonary hypertension of unknown cause</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TFN2"><p>CPOD: chronic pulmonary obstructive disease.</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec>
<title>Protocol of IHM in HFpEF</title>
<p>We adopt and recommend the HFpEF assessment protocol proposed by Borlaug et al.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup> (<xref ref-type="table" rid="t3">Table 3</xref>). It is recommended that the patient receives a brief training to perform exercises using an in-bed cycle ergometry, as it contributes to the venous return and increases the elevation in pulmonary capillary pressure (<xref ref-type="fig" rid="f1">Figure 1</xref>). For obese patients who cannot tolerate the supine position, it is recommended to raise the head of the bed up to a 45-degree angle. Both situations should be carried out with the patient under continuous electrocardiographic monitoring and digital oximetry, breathing room temperature air. For patients with atrial fibrillation, it is recommended a good heart rate control before IHM, and that the patient is not dehydrated for excessive use of diuretics.</p>
<table-wrap id="t3">
<label>Table 3</label>
<caption><title>Steps of the invasive hemodynamic monitoring in the diagnosis of heart failure with preserved ejection fraction</title></caption>
<table frame="hsides" rules="rows">
<colgroup width="50%">
<col/>
<col/>
</colgroup>
<tbody style="border-bottom: thin solid; border-color: #000000">
<tr>
<td align="left" valign="middle">1</td>
<td align="left" valign="middle">Puncture of the right internal jugular vein and placement of an 8F introducer for Swan-Ganz catheterization</td>
</tr>
<tr>
<td align="left" valign="middle">2</td>
<td align="left" valign="middle">Puncture of the right or left radial artery with a 5F introducer for catheterization of the left ventricular cavity with a 5F pigtail catheter and measurement of blood pressure and left ventricular end diastolic</td>
</tr>
<tr>
<td align="left" valign="middle">3</td>
<td align="left" valign="middle">Place the Swan-Ganz catheter in zone 2 to obtain pulmonary capillary wedge pressure (typical capillary pressure curve)</td>
</tr>
<tr>
<td align="left" valign="middle">4</td>
<td align="left" valign="middle">Install the pressure transducers, zeroed at the level of the mid-axillary line, for measurements of pressures in the right atrium, right ventricle and pulmonary artery, pulmonary capillary pressure and left ventricular end diastolic pressure and mean arterial pressure. Measures are taken according to cardiac cycle (at the end of ventricular diastole) and if possible, at the end of exhale</td>
</tr>
<tr>
<td align="left" valign="middle">5</td>
<td align="left" valign="middle">Measure baseline blood pressure and cardiac output at rest. In patients with atrial fibrillation, mean blood pressure should be obtained from 10 consecutive heart beats. Measurements are obtained by a polygraph and printed by a printer coupled to the system</td>
</tr>
<tr>
<td align="left" valign="middle">6</td>
<td align="left" valign="middle">Adjust the patient feet on the ergometer pedals and fix them with an adhesive tape</td>
</tr>
<tr>
<td align="left" valign="middle">7</td>
<td align="left" valign="middle">Initiate the exercise protocol at 20 Watts and 60 revolutions per minute (rpm) for three minutes, advance to the next stage (workload of 40 watts) for another three minutes. At patient&#x27;s maximum effort or maximum tolerance, take blood pressure and cardiac output measurements</td>
</tr>
<tr>
<td align="left" valign="middle">8</td>
<td align="left" valign="middle">After five minutes at rest, take blood pressure measurements</td>
</tr>
<tr>
<td align="left" valign="middle">9</td>
<td align="left" valign="middle">As most patients have coronary disease risk factors, perform coronary cineangiography before removing the radial line</td>
</tr>
<tr>
<td align="left" valign="middle">10</td>
<td align="left" valign="middle">After the test, analyze pressure curves and cardiac output measurements, and calculate pulmonary vascular and systemic resistances, transpulmonary and pulmonary diastolic gradients, and eventual left ventricular gradient/end diastolic pressure</td>
</tr>
<tr>
<td align="left" valign="middle">11</td>
<td align="left" valign="middle">A diagnosis of HFpEF is confirmed by resting pulmonary capillary pressure or left ventricular end diastolic pressure &#x2265; 15 mmHg at rest and &#x2265; 25 mmHg during exercise</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TFN3"><p>HFpEF: heart failure with preserved ejection fraction.</p></fn>
</table-wrap-foot>
</table-wrap>
<fig id="f1">
<label>Figure 1</label>
<caption><title>Simulation of patient positioning for invasive hemodynamic monitoring in the diagnosis of heart failure with preserved ejection fraction.</title></caption>
<graphic xlink:href="2764-3107-abchf-002-03-0290-gf01.tif"/>
</fig>
<p>We now describe the steps involved in IHM in the diagnosis of HFpEF. The protocol recommends that the test is started with a workload of 20 watts for three minutes (first stage), followed by an increase to 40 watts for three minutes (second stage). Studies have shown that filling pressures rise to abnormal levels as early as at the end of the first stage<sup><xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup> and rapidly return to baseline values after effort interruption (<xref ref-type="fig" rid="f2">Figure 2</xref>).<sup><xref ref-type="bibr" rid="B31">31</xref>&#x2013;<xref ref-type="bibr" rid="B33">33</xref></sup></p>
<fig id="f2">
<label>Figure 2</label>
<caption><title>Temporal magnitude representation of the increase in pulmonary capillary pressure and left ventricular end diastolic pressure during exercise in patients with heart failure with preserved ejection fraction (Obokata et al. Circulation 2017; 135:825-38, authorized by the author). LVEDP: left ventricular end diastolic pressure; HFpEF: heart failure with preserved ejection fraction; BP: blood pressure; NCD: non-cardiac dyspnea.</title></caption>
<graphic xlink:href="2764-3107-abchf-002-03-0290-gf02.tif"/>
</fig>
</sec>
<sec>
<title>Interpretation of IHM</title>
<p>An adequate interpretation of the IHM results requires the analysis of curves of filling pressure, right cavity pressure, pulmonary pressure, and left ventricular end diastolic pressure, obtained preferably at the end of exhalation at rest and at maximum effort (<xref ref-type="fig" rid="f3">Figure 3</xref>).</p>
<fig id="f3">
<label>Figure 3</label>
<caption><title>Representation of pulmonary capillary pressure (PCWP) and left ventricular end diastolic pressure (LVEDP) curves at rest and at maximum effort of a patient with heart failure with preserved ejection fraction; adapted from Barry et al.<sup><xref ref-type="bibr" rid="B25">25</xref></sup></title></caption>
<graphic xlink:href="2764-3107-abchf-002-03-0290-gf03.tif"/>
</fig>
<p>The integrated analysis of all hemodynamic parameters obtained both at rest and during exercise will allow confirmation or exclusion of HFpEF as the cause of symptoms. Values of left ventricular end diastolic pressure may replace pulmonary capillary pressure, especially in case of atrial fibrillation or of suboptimal quality of pulmonary capillary pressure curves due to the presence of V wave due to mitral regurgitation. The diagnosis of HFpEF is established when pulmonary capillary pressure &#x2265;15mmHg at rest or &#x2265;25 mmHg during exercise.<sup><xref ref-type="bibr" rid="B22">22</xref>&#x2013;<xref ref-type="bibr" rid="B24">24</xref>,<xref ref-type="bibr" rid="B34">34</xref></sup> In case of atrial fibrillation, mean pressure of 10 consecutive cardiac cycles should be considered, and extrasystoles excluded. It is worth pointing out that normal blood pressure at rest do not rule out the diagnosis of HFpEF, and it is mandatory to repeat all measures during exercise.<sup><xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B33">33</xref>,<xref ref-type="bibr" rid="B35">35</xref></sup> If patients are not able to move their legs, arm exercises, volume overload test, passive leg raise maneuver or even a combination of these may be used as alternatives.<sup><xref ref-type="bibr" rid="B29">29</xref>,<xref ref-type="bibr" rid="B30">30</xref>,<xref ref-type="bibr" rid="B35">35</xref>,<xref ref-type="bibr" rid="B36">36</xref></sup></p>
<p>In conclusion, in light of the difficulties of establishing the diagnosis of HFpEF due to the low sensitivity and specificity of invasive methods, especially when of those performed at rest, IHM during exercise has emerged as the gold standard for the diagnosis of HFpEF because of objectivity of filling pressure measurements and high sensitivity and specificity rates, with positive and negative predictive values of nearly 100%.<sup><xref ref-type="bibr" rid="B32">32</xref>,<xref ref-type="bibr" rid="B33">33</xref></sup> This is a safe method that can be used in most patients with a HFpEF phenotype, including patients with an intermediate risk score, patients with dyspnea or pulmonary hypertension of unknown origin after non-invasive tests were performed.<sup><xref ref-type="bibr" rid="B23">23</xref>&#x2013;<xref ref-type="bibr" rid="B25">25</xref></sup></p>
</sec>
</sec>
</body>
<back>
<fn-group>
<fn fn-type="supported-by" id="fn1">
<p><bold>Sources of Funding</bold></p>
<p>There were no external funding sources for this study.</p></fn>
<fn fn-type="other" id="fn2">
<p><bold>Study Association</bold></p>
<p>This study is not associated with any thesis or dissertation work.</p></fn>
<fn fn-type="other" id="fn3">
<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-group>
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<article-title>Differential Hemodynamic Effects of Exercise and Volume Expansion in People with and Without Heart Failure</article-title>
<source>Circ Heart Fail</source>
<year>2015</year>
<volume>8</volume>
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<fpage>41</fpage>
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<pub-id pub-id-type="doi">10.1161/CIRCHEARTFAILURE.114.001731</pub-id>
</element-citation>
<mixed-citation>Andersen MJ, Olson TP, Melenovsky V, Kane GC, Borlaug BA. Differential Hemodynamic Effects of Exercise and Volume Expansion in People with and Without Heart Failure. Circ Heart Fail. 2015;8(1):41-8. doi: 10.1161/CIRCHEARTFAILURE.114.001731.</mixed-citation>
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<name><surname>Shin</surname><given-names>JH</given-names></name>
<name><surname>Park</surname><given-names>WC</given-names></name>
<name><surname>Kim</surname><given-names>SG</given-names></name>
<name><surname>Shin</surname><given-names>J</given-names></name>
<name><surname>Lim</surname><given-names>YH</given-names></name>
<etal/>
</person-group>
<article-title>Two Distinct Responses of Left Ventricular End-Diastolic Pressure to Leg-Raise Exercise in Euvolemic Patients with Exertional Dyspnea</article-title>
<source>Korean Circ J</source>
<year>2016</year>
<volume>46</volume>
<issue>3</issue>
<fpage>350</fpage>
<lpage>364</lpage>
<pub-id pub-id-type="doi">10.4070/kcj.2016.46.3.350</pub-id>
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<mixed-citation>Choi S, Shin JH, Park WC, Kim SG, Shin J, Lim YH, et al. Two Distinct Responses of Left Ventricular End-Diastolic Pressure to Leg-Raise Exercise in Euvolemic Patients with Exertional Dyspnea. Korean Circ J. 2016;46(3):350-64. doi: 10.4070/kcj.2016.46.3.350.</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>Artigo de Revis&#xE3;o</subject></subj-group></article-categories>
<title-group>
<article-title>Avalia&#xE7;&#xE3;o Hemodin&#xE2;mica Invasiva no Diagn&#xF3;stico da Insufici&#xEA;ncia Card&#xED;aca com Fra&#xE7;&#xE3;o de Eje&#xE7;&#xE3;o Preservada</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-2178-1518</contrib-id>
<name><surname>Almeida</surname><given-names>Dirceu Rodrigues</given-names></name>
<role>Concep&#xE7;&#xE3;o e desenho da pesquisa</role>
<role>Obten&#xE7;&#xE3;o de dados</role>
<role>An&#xE1;lise e interpreta&#xE7;&#xE3;o dos dados</role>
<role>An&#xE1;lise estat&#xED;stica</role>
<role>Obten&#xE7;&#xE3;o de financiamento</role>
<role>Reda&#xE7;&#xE3;o do manuscrito</role>
<role>Revis&#xE3;o cr&#xED;tica do manuscrito quanto ao conte&#xFA;do intelectual importante</role>
<xref ref-type="aff" rid="aff2"/><xref ref-type="corresp" rid="c2"/>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-2612-8040</contrib-id>
<name><surname>Andrade</surname><given-names>Fernanda Almeida</given-names></name>
<role>Concep&#xE7;&#xE3;o e desenho da pesquisa</role>
<role>Obten&#xE7;&#xE3;o de dados</role>
<role>An&#xE1;lise e interpreta&#xE7;&#xE3;o dos dados</role>
<role>An&#xE1;lise estat&#xED;stica</role>
<role>Obten&#xE7;&#xE3;o de financiamento</role>
<role>Reda&#xE7;&#xE3;o do manuscrito</role>
<role>Revis&#xE3;o cr&#xED;tica do manuscrito quanto ao conte&#xFA;do intelectual importante</role>
<xref ref-type="aff" rid="aff2"/>
</contrib>
<aff id="aff2">
<label>1</label>
<addr-line>
<named-content content-type="city">S&#xE3;o Paulo</named-content>
<named-content content-type="state">SP</named-content>
</addr-line>
<country country="BR">Brasil</country>
<institution content-type="original">Universidade Federal de S&#xE3;o Paulo (UNIFESP) S&#xE3;o Paulo, SP &#x2013; Brasil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c2"><bold>Correspond&#xEA;ncia: Dirceu Rodrigues Almeida</bold> &#x2022; Universidade Federal de S&#xE3;o Paulo &#x2013; Rua Botucatu, 830. CEP <postal-code>04021-001</postal-code>, S&#xE3;o Paulo, SP &#x2013; Brasil. E-mail: <email>dirceualmeida.unifesp@gmail.com</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>
</author-notes>
<kwd-group xml:lang="pt">
<title>Palavras-chave</title>
<kwd>Insufici&#xEA;ncia Card&#xED;aca</kwd>
<kwd>Insufici&#xEA;ncia Card&#xED;aca Diast&#xF3;lica</kwd>
<kwd>Diagn&#xF3;stico</kwd>
</kwd-group>
</front-stub>
<body>
<sec sec-type="intro">
<title>Introdu&#xE7;&#xE3;o</title>
<p>A insufici&#xEA;ncia card&#xED;aca com fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o preservada (ICFEP) &#xE9; uma s&#xED;ndrome cl&#xED;nica complexa com impacto negativo na qualidade de vida e na expectativa de vida dos pacientes, com altas taxas de hospitaliza&#xE7;&#xE3;o e mortalidade. A preval&#xEA;ncia da ICFEP &#xE9; extremamente alta, provavelmente devido &#xE0; crescente preval&#xEA;ncia dos fatores de risco comuns, como idade avan&#xE7;ada, sexo feminino, hipertens&#xE3;o arterial, diabetes, disfun&#xE7;&#xE3;o renal e obesidade.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup> Estima-se que cerca de metade dos pacientes que se apresentam com insufici&#xEA;ncia card&#xED;aca tem fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o preservada, definida como fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o do ventr&#xED;culo esquerdo (FEVE) maior ou igual a 50%. A despeito de centenas de publica&#xE7;&#xF5;es de artigos originais, revis&#xF5;es, livros-texto e diretrizes, ainda existem d&#xFA;vidas e controv&#xE9;rsias sobre a sua real incid&#xEA;ncia, etiopatogenia, fisiopatologia, progn&#xF3;stico e principalmente sobre as dificuldades para o seu correto diagn&#xF3;stico com as metodologias n&#xE3;o invasivas. Neste artigo, ressaltaremos a import&#xE2;ncia da avalia&#xE7;&#xE3;o hemodin&#xE2;mica invasiva (AHI) para o correto diagn&#xF3;stico da ICFEP.<sup><xref ref-type="bibr" rid="B1">1</xref>&#x2013;<xref ref-type="bibr" rid="B4">4</xref></sup></p>
<sec>
<title>Diagn&#xF3;stico n&#xE3;o invasivo da insufici&#xEA;ncia card&#xED;aca com fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o preservada</title>
<p>Antes de abordar o papel da AHI no diagn&#xF3;stico da ICFEP faremos uma breve considera&#xE7;&#xE3;o sobre as ferramentas n&#xE3;o invasivas dispon&#xED;veis para esse prop&#xF3;sito, destacando principalmente suas limita&#xE7;&#xF5;es.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
<p>Em raz&#xE3;o das dificuldades ou mesmo da impossibilidade de um diagn&#xF3;stico diferencial cl&#xED;nico entre ICFEP e insufici&#xEA;ncia card&#xED;aca com fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o reduzida (ICFER), todos os consensos recomendam a ecocardiografia bidimensional com doppler collor para avalia&#xE7;&#xE3;o objetiva da fun&#xE7;&#xE3;o ventricular, com c&#xE1;lculo da FEVE e estudo detalhado da fun&#xE7;&#xE3;o diast&#xF3;lica.<sup><xref ref-type="bibr" rid="B6">6</xref>&#x2013;<xref ref-type="bibr" rid="B9">9</xref></sup> Na avalia&#xE7;&#xE3;o da fun&#xE7;&#xE3;o diast&#xF3;lica, vamos analisar v&#xE1;rios par&#xE2;metros da ecocardiografia (fluxo mitral, doppler tecidual, volume e &#xE1;rea de &#xE1;trio esquerdo e press&#xE3;o estimada da art&#xE9;ria pulmonar), os quais em conjunto podem permitir o diagn&#xF3;stico da ICFEP.<sup><xref ref-type="bibr" rid="B6">6</xref>&#x2013;<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B10">10</xref></sup></p>
<p>A an&#xE1;lise do fluxo mitral &#xE9; o passo inicial na avalia&#xE7;&#xE3;o da fun&#xE7;&#xE3;o diast&#xF3;lica em pacientes com ritmo sinusal. Pelo doppler, &#xE9; poss&#xED;vel determinar as ondas inicial (E) e tardia (A) do enchimento ventricular esquerdo (VE).<sup><xref ref-type="bibr" rid="B10">10</xref></sup> A onda E representa a fase de enchimento r&#xE1;pido do VE, por diferen&#xE7;a de press&#xE3;o, enquanto a onda A representa o enchimento ativo pela contra&#xE7;&#xE3;o atrial. A di&#xE1;stole &#xE9; analisada pela rela&#xE7;&#xE3;o entre as velocidades das ondas E e A em conjunto com o tempo de desacelera&#xE7;&#xE3;o da onda E. A velocidade da onda E pode ser analisada juntamente com o Doppler tecidual como veremos adiante. Em indiv&#xED;duos normais, a rela&#xE7;&#xE3;o entre as velocidades das ondas E e A &#x2013; rela&#xE7;&#xE3;o E/A - &#xE9; maior que 1.0. Com o envelhecimento, ocorre um enrijecimento do VE, causando retardo no relaxamento, ou seja, h&#xE1; redu&#xE7;&#xE3;o da velocidade da onda E e menor tempo de desacelera&#xE7;&#xE3;o desta onda, al&#xE9;m de aumento da velocidade da onda A, tornando a rela&#xE7;&#xE3;o E/A menor que 1.0. Este padr&#xE3;o de enchimento &#xE9; conhecido como altera&#xE7;&#xE3;o do relaxamento; por&#xE9;m, &#xE9; importante assinalar que esse padr&#xE3;o n&#xE3;o implica em uma patologia em si e n&#xE3;o significa, na maioria dos pacientes, aumento da press&#xE3;o de enchimento ou da press&#xE3;o diast&#xF3;lica final do VE.</p>
<p>Nos pacientes que apresentam redu&#xE7;&#xE3;o da complac&#xEA;ncia do VE e aumento da press&#xE3;o diast&#xF3;lica do VE, observa-se equaliza&#xE7;&#xE3;o r&#xE1;pida das press&#xF5;es do &#xE1;trio esquerdo (AE) e do VE, resultando em interrup&#xE7;&#xE3;o precoce do influxo de sangue. Com isso, observamos aumento da velocidade e diminui&#xE7;&#xE3;o do tempo de desacelera&#xE7;&#xE3;o da onda E associado a diminui&#xE7;&#xE3;o da velocidade da onda A. A partir destas altera&#xE7;&#xF5;es, o padr&#xE3;o de enchimento passa a ser semelhante ao padr&#xE3;o normal, sendo assim designado de padr&#xE3;o de enchimento pseudonormal que implica em prov&#xE1;vel altera&#xE7;&#xE3;o diast&#xF3;lica patol&#xF3;gica. A diferencia&#xE7;&#xE3;o entre o padr&#xE3;o pseudonormal e o normal pode ser feita pela manobra de valsalva, &#xE0; medida que aumentam a press&#xE3;o diast&#xF3;lica e as press&#xF5;es de enchimento do VE. Essas &#xFA;ltimas altera&#xE7;&#xF5;es do fluxo mitral tendem a se acentuar, com aumento maior da rela&#xE7;&#xE3;o E/A (para n&#xED;veis maiores que 2.0), redu&#xE7;&#xE3;o maior do tempo de desacelera&#xE7;&#xE3;o da onda E e da velocidade da onda A, caracterizando o padr&#xE3;o restritivo de enchimento do VE que tamb&#xE9;m implica em prov&#xE1;vel disfun&#xE7;&#xE3;o diast&#xF3;lica patol&#xF3;gica.<sup><xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B12">12</xref></sup> Cabe salientar que a an&#xE1;lise da rela&#xE7;&#xE3;o E/A tem limita&#xE7;&#xF5;es importantes para diagn&#xF3;stico de ICFEP por depender de vari&#xE1;veis, como: frequ&#xEA;ncia card&#xED;aca, arritmia, pr&#xE9;-carga (volemia) e p&#xF3;s-carga (hipertens&#xE3;o). Assim, essa avalia&#xE7;&#xE3;o s&#xF3; pode ser realizada com precis&#xE3;o em pacientes em ritmo sinusal e com frequ&#xEA;ncia card&#xED;aca normal.<sup><xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B11">11</xref></sup></p>
<p>O ecocardiograma Doppler tecidual &#xE9; uma t&#xE9;cnica que mensura a velocidade de deslocamento do mioc&#xE1;rdio basal e a movimenta&#xE7;&#xE3;o do anel mitral. A obten&#xE7;&#xE3;o das curvas do doppler tecidual &#xE9; realizada no corte apical 4-c&#xE2;maras, no anel mitral septal e lateral, onde &#xE9; poss&#xED;vel verificar a velocidade de tr&#xEA;s ondas: diast&#xF3;lica inicial (e&#xB4;), diast&#xF3;lica final (a&#xB4;) e sist&#xF3;lica (s). Na presen&#xE7;a de altera&#xE7;&#xE3;o do relaxamento, independente das press&#xF5;es de enchimento do VE, a velocidade da onda e&#x2019; est&#xE1; reduzida. A maior import&#xE2;ncia desse m&#xE9;todo na avalia&#xE7;&#xE3;o da fun&#xE7;&#xE3;o diast&#xF3;lica decorre da avalia&#xE7;&#xE3;o conjunta ao doppler do fluxo mitral, particularmente pelo uso da rela&#xE7;&#xE3;o entre as velocidades da onda E mitral com a onda e&#xB4; (septal, lateral ou m&#xE9;dia) do doppler tecidual. A rela&#xE7;&#xE3;o E/e&#xB4; tem sido utilizada como uma medida indireta da press&#xE3;o capilar pulmonar ou press&#xE3;o diast&#xF3;lica final do VE. Entretanto, em pacientes com ICFEP a avalia&#xE7;&#xE3;o dos par&#xE2;metros de enchimento ventricular incluindo a rela&#xE7;&#xE3;o E/e&#x2019; comparado &#xE0; medida das press&#xF5;es de enchimento obtidas pelo estudo hemodin&#xE2;mico invasivo simult&#xE2;neo tem baixa ou, no m&#xE1;ximo, moderado valor preditivo para estimar as press&#xF5;es de enchimento.<sup><xref ref-type="bibr" rid="B13">13</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup> A fraca correla&#xE7;&#xE3;o do E/e&#x2019; com as medidas hemodin&#xE2;micas ocorrem principalmente quando a rela&#xE7;&#xE3;o E/e&#x2019; se encontra abaixo de 15. Cabe ressaltar que a obten&#xE7;&#xE3;o da rela&#xE7;&#xE3;o E/e&#x2019; depende de janela ecocardiogr&#xE1;fica adequada e da presen&#xE7;a do ritmo sinusal, e sofre influ&#xEA;ncia de altera&#xE7;&#xF5;es valvares como a calcifica&#xE7;&#xE3;o do anel mitral e presen&#xE7;a de insufici&#xEA;ncia mitral, ambas frequentes nas pessoas idosas.<sup><xref ref-type="bibr" rid="B12">12</xref>&#x2013;<xref ref-type="bibr" rid="B14">14</xref></sup></p>
<p>A interpreta&#xE7;&#xE3;o dos par&#xE2;metros ecocardiogr&#xE1;ficos discutidos deve ser vista com cautela quando n&#xE3;o se encontram alterados em repouso, visto que a maioria dos pacientes com ICFEP apresentam sintomas apenas aos esfor&#xE7;os, pelo aumento das press&#xF5;es de enchimento. Logo, a realiza&#xE7;&#xE3;o de medidas ecocardiogr&#xE1;ficas, especialmente a rela&#xE7;&#xE3;o E/&#xE9; durante o esfor&#xE7;o (stress diast&#xF3;lico) pode ser &#xFA;til por ser mais sens&#xED;vel na avalia&#xE7;&#xE3;o destes pacientes. A rela&#xE7;&#xE3;o E/e&#xB4; mant&#xE9;m-se constante durante o esfor&#xE7;o nos indiv&#xED;duos normais, por&#xE9;m aumenta nos pacientes com disfun&#xE7;&#xE3;o diast&#xF3;lica do VE, apresentando rela&#xE7;&#xE3;o com o aumento das press&#xF5;es de enchimento e press&#xE3;o pulmonar. Assim, sua realiza&#xE7;&#xE3;o deve ser sempre considerada em pacientes com fen&#xF3;tipo para ICFEP e cl&#xED;nica de insufici&#xEA;ncia card&#xED;aca quando a rela&#xE7;&#xE3;o E/e&#x2019; for inferior a 15.<sup><xref ref-type="bibr" rid="B13">13</xref>&#x2013;<xref ref-type="bibr" rid="B18">18</xref></sup> A realiza&#xE7;&#xE3;o simult&#xE2;nea do ultrassom pulmonar durante a ecocardiografia de esfor&#xE7;o pode demonstrar o aparecimento da congest&#xE3;o pulmonar durante o stress diast&#xF3;lico que indica eleva&#xE7;&#xE3;o da press&#xE3;o capilar pulmonar.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> As limita&#xE7;&#xF5;es da ecocardiografia de esfor&#xE7;o s&#xE3;o decorrentes de sua n&#xE3;o incorpora&#xE7;&#xE3;o na rotina da maioria dos laborat&#xF3;rios de ecocardiografia, de janela ecocardiografia inadequada, da depend&#xEA;ncia na experi&#xEA;ncia do operador para obten&#xE7;&#xE3;o dos par&#xE2;metros hemodin&#xE2;micos, al&#xE9;m do fato de que a taquipneia do paciente no esfor&#xE7;o limita a obten&#xE7;&#xE3;o de imagem de qualidade. Somente 50% dos pacientes tem janela ecocardiogr&#xE1;fica adequada para obten&#xE7;&#xE3;o de imagens de boa qualidade durante o esfor&#xE7;o. A presen&#xE7;a de fibrila&#xE7;&#xE3;o atrial &#xE9; um fator limitante que corrobora para baixa acur&#xE1;cia do ecocardiograma em avaliar as press&#xF5;es de enchimento e da press&#xE3;o pulmonar no esfor&#xE7;o.<sup><xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B13">13</xref></sup></p>
<p>Em raz&#xE3;o das limita&#xE7;&#xF5;es dos m&#xE9;todos n&#xE3;o invasivos aqui apontadas e da aus&#xEA;ncia de consenso quanto &#xE0; melhor forma de se fazer o diagn&#xF3;stico da ICFEP, alguns autores t&#xEA;m tentado estabelecer crit&#xE9;rios uniformes para o diagn&#xF3;stico. Diante das dificuldades em se firmar o diagn&#xF3;stico n&#xE3;o invasivo da ICFEP, ferramentas denominadas escores diagn&#xF3;sticos s&#xE3;o importantes para refor&#xE7;ar a suspeita cl&#xED;nica e para triar os pacientes para estudo hemodin&#xE2;mico invasivo.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup></p>
<p>O escore mais utilizado por ser de mais f&#xE1;cil obten&#xE7;&#xE3;o &#xE9; escore H2FPEF (<xref ref-type="table" rid="t4">Tabela 1</xref>) de f&#xE1;cil realiza&#xE7;&#xE3;o, pr&#xE1;tico e com boa acur&#xE1;cia.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> O modelo de diagn&#xF3;stico desse escore foi desenvolvido em uma coorte de pacientes com dispneia inexplicada que foram referenciados para cateterismo direito com teste de esfor&#xE7;o. Utiliza seis vari&#xE1;veis cl&#xED;nicas e ecocardiogr&#xE1;ficas: idade &#x3E; 60 anos, &#xED;ndice de massa corporal (IMC) &#x3E; 30 kg / m<sup>2</sup>, hipertens&#xE3;o arterial com &#x2265; 2 medicamentos anti-hipertensivos, presen&#xE7;a de fibrila&#xE7;&#xE3;o atrial (FA) permanente ou parox&#xED;stica, rela&#xE7;&#xE3;o E/e&#xB4;&#x3E;9 e press&#xE3;o sist&#xF3;lica da art&#xE9;ria pulmonar &#x3E;35 mmHg (par&#xE2;metros ecocardiogr&#xE1;ficos). A vari&#xE1;vel fibrila&#xE7;&#xE3;o atrial recebe 3 pontos e a vari&#xE1;vel IMC &#x3E; 30 recebe 2 pontos, enquanto as demais recebem 1 ponto cada. O escore H2FPEF teve bom desempenho discriminat&#xF3;rio (&#xE1;rea sob a curva operacional de 0,84) e superior ao escore HFA-PEFF em sensibilidade e especificidade para refutar ou identificar os portadores de ICFEP.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> Ao estabelecer a probabilidade de doen&#xE7;a, o escore H2FPEF pode ser usado para descartar efetivamente a doen&#xE7;a entre pacientes com escores baixos (por exemplo, 0 ou 1), para estabelecer o diagn&#xF3;stico com confian&#xE7;a razoavelmente boa em escores mais altos (por exemplo, acima de 9). Assim, o HF2pEF deve ser usado para identificar pacientes com pontua&#xE7;&#xF5;es intermedi&#xE1;rias (por exemplo de 2-9), que necessitar&#xE3;o de testes adicionais.<sup><xref ref-type="bibr" rid="B19">19</xref>,<xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B23">23</xref></sup></p>
<table-wrap id="t4">
<label>Tabela 1</label>
<caption><title>Escore H2FPEF para o diagn&#xF3;stico de ICFEP</title></caption>
<table frame="hsides" rules="rows">
<colgroup width="25%">
<col/>
<col/>
<col/>
<col/>
</colgroup>
<thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
<tr>
<th align="center" valign="middle"/>
<th align="left" valign="middle">Vari&#xE1;veis Cl&#xED;nicas</th>
<th align="center" valign="middle">Valores</th>
<th align="center" valign="middle">Pontos</th>
</tr>
</thead>
<tbody style="border-bottom: thin solid; border-color: #000000">
<tr>
<td align="left" valign="middle" rowspan="2">H2</td>
<td align="center" valign="middle">Peso (Heavy)</td>
<td align="center" valign="middle">IMC &#x3E; 30kg/m&#xB2;</td>
<td align="center" valign="middle">2</td>
</tr>
<tr>
<td align="center" valign="middle">Hipertens&#xE3;o Arterial</td>
<td align="center" valign="middle">&#x2265; anti-hipertensivos</td>
<td align="center" valign="middle">1</td>
</tr>
<tr>
<td align="left" valign="middle">F</td>
<td align="center" valign="middle">Fibrila&#xE7;&#xE3;o Atrial</td>
<td align="center" valign="middle">Parox&#xED;stica ou persistente</td>
<td align="center" valign="middle">3</td>
</tr>
<tr>
<td align="left" valign="middle">P</td>
<td align="center" valign="middle">Hipertens&#xE3;o Pulmonar</td>
<td align="center" valign="middle">PSAP &#x2265;35mmHg</td>
<td align="center" valign="middle">1</td>
</tr>
<tr>
<td align="left" valign="middle">E</td>
<td align="center" valign="middle">Idoso (Elder)</td>
<td align="center" valign="middle">&#x3E; 60 anos</td>
<td align="center" valign="middle">1</td>
</tr>
<tr>
<td align="left" valign="middle">F</td>
<td align="center" valign="middle">Press&#xE3;o de Enchimento (Filling Pressure)</td>
<td align="center" valign="middle">E/e&#xB4;&#x3E; 9</td>
<td align="center" valign="middle">1</td>
</tr>
</tbody>
</table>
<table frame="hsides" rules="rows">
<colgroup width="10%">
<col/>
<col/>
<col/>
<col/>
<col/>
<col/>
<col/>
<col/>
<col/>
<col/>
</colgroup>
<tbody style="border-bottom: thin solid; border-color: #000000">
<tr>
<td align="left" valign="middle" colspan="10"><bold>Total de pontos</bold></td>
</tr>
<tr>
<td align="left" valign="middle">0</td>
<td align="left" valign="middle">1</td>
<td align="left" valign="middle">2</td>
<td align="left" valign="middle">3</td>
<td align="left" valign="middle">4</td>
<td align="left" valign="middle">5</td>
<td align="left" valign="middle">6</td>
<td align="left" valign="middle">7</td>
<td align="left" valign="middle">8</td>
<td align="left" valign="middle">9</td>
</tr>
<tr style="background-color:#ED1C24">
<td align="left" valign="middle">0.2</td>
<td align="left" valign="middle">0.3</td>
<td align="left" valign="middle">0.4</td>
<td align="left" valign="middle">0.5</td>
<td align="left" valign="middle">0.6</td>
<td align="left" valign="middle">0.7</td>
<td align="left" valign="middle">0.8</td>
<td align="left" valign="middle">0.9</td>
<td align="left" valign="middle">0.96</td>
<td align="left" valign="middle" />
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TFN4"><p>IMC: &#xED;ndice de massa corporal; PSAP: press&#xE3;o sist&#xF3;lica da art&#xE9;ria pulmonar</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec>
<title>Probabilidade de ICFEP</title>
<p>Os escores diagn&#xF3;sticos dispon&#xED;veis em aplicativos s&#xE3;o ferramentas que podem ser &#xFA;teis na pr&#xE1;tica cl&#xED;nica. Os escores trazem informa&#xE7;&#xF5;es acerca da probabilidade diagn&#xF3;stica de ICFEP com aceit&#xE1;veis sensibilidade e especificidade. Assim, pacientes com baixa ou alta probabilidade de diagn&#xF3;stico s&#xE3;o identificados, bem como os pacientes de probabilidade intermedi&#xE1;ria s&#xE3;o triados para exames mais definitivos como a avalia&#xE7;&#xE3;o hemodin&#xE2;mica invasiva que proporciona medidas diretas das press&#xF5;es de enchimento (press&#xE3;o capilar pulmonar e/ou press&#xE3;o diast&#xF3;lica final do ventr&#xED;culo esquerdo) e press&#xE3;o arterial pulmonar em repouso e no esfor&#xE7;o.<sup><xref ref-type="bibr" rid="B21">21</xref></sup></p>
</sec>
<sec>
<title>Avalia&#xE7;&#xE3;o hemodin&#xE2;mica invasiva (AHI) na ICFEP</title>
<p>Dispneia de esfor&#xE7;o &#xE9; comum em pacientes com doen&#xE7;as cardiopulmonares. Para o esclarecimento etiol&#xF3;gico da dispneia na pr&#xE1;tica cl&#xED;nica, empregamos dados epidemiol&#xF3;gicos, hist&#xF3;ria cl&#xED;nica e exame f&#xED;sico. Exames como espirometria, teste cardiopulmonar (TCP) e exames de imagem permitem diagnosticar as doen&#xE7;as que comprometem a fun&#xE7;&#xE3;o ventilat&#xF3;ria.<sup><xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B23">23</xref></sup> Na avalia&#xE7;&#xE3;o cardiol&#xF3;gica, a ecocardiografia &#xE9; sempre empregada, contudo, infelizmente &#xE9; realizada apenas em repouso. Ainda, n&#xE3;o s&#xE3;o consideradas v&#xE1;rias limita&#xE7;&#xF5;es do teste, dentre elas a janela inadequada (pela obesidade, deformidade tor&#xE1;cica, hiperinsufla&#xE7;&#xE3;o pulmonar) e, principalmente, a presen&#xE7;a de fibrila&#xE7;&#xE3;o atrial, situa&#xE7;&#xE3;o que impede qualquer avalia&#xE7;&#xE3;o de fun&#xE7;&#xE3;o diast&#xF3;lica.<sup><xref ref-type="bibr" rid="B14">14</xref>&#x2013;<xref ref-type="bibr" rid="B16">16</xref></sup></p>
<p>A diferencia&#xE7;&#xE3;o entre causa pulmonar ou card&#xED;aca de dispneia deve contemplar sempre a possibilidade de ICFEP, visto que essa &#xE9; respons&#xE1;vel por 30 a 50% dos casos de dispneia ou hipertens&#xE3;o pulmonar a esclarecer em pacientes submetidos &#xE0; AHI.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B23">23</xref>,<xref ref-type="bibr" rid="B24">24</xref></sup> O estudo hemodin&#xE2;mico invasivo em repouso e com esfor&#xE7;o &#xE9; o m&#xE9;todo mais poderoso para avaliar as causas de dispneia aos esfor&#xE7;os e de hipertens&#xE3;o pulmonar. &#xC9; considerado hoje o m&#xE9;todo gold standard para o diagn&#xF3;stico de ICFEP, possibilitando a medida direta das press&#xF5;es de enchimento ventricular, bem como a aferi&#xE7;&#xE3;o da press&#xE3;o pulmonar, do d&#xE9;bito card&#xED;aco, e da resist&#xEA;ncia vascular pulmonar.<sup><xref ref-type="bibr" rid="B24">24</xref>&#x2013;<xref ref-type="bibr" rid="B26">26</xref></sup> Tem grande utilidade tamb&#xE9;m em pacientes com doen&#xE7;a mista, como insufici&#xEA;ncia card&#xED;aca e doen&#xE7;a pulmonar, sendo capaz de nos informar se o fator mais limitante para o esfor&#xE7;o &#xE9; predominantemente de causa card&#xED;aca ou pulmonar.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup></p>
<p>As diretrizes atuais para diagn&#xF3;stico de ICFEP enfatiza as limita&#xE7;&#xF5;es dos dados ecocardiogr&#xE1;ficos obtidos em repouso pela sua baixa sensibilidade ou baixa especificidade, al&#xE9;m das limita&#xE7;&#xF5;es t&#xE9;cnicas para a obten&#xE7;&#xE3;o dos par&#xE2;metros ecocardiogr&#xE1;ficos de avalia&#xE7;&#xE3;o da fun&#xE7;&#xE3;o diast&#xF3;lica. Sugerem ent&#xE3;o que a ecocardiografia com esfor&#xE7;o deve ser empregada para o diagn&#xF3;stico de ICFEP, embora ainda existam muitas limita&#xE7;&#xF5;es relacionadas. Assim, a medida direta das press&#xF5;es de enchimento em repouso e no esfor&#xE7;o &#xE9; a &#xFA;nica ferramenta capaz de excluir o diagn&#xF3;stico de ICFEP devido aos seus altos valores de sensibilidade (100%) e especificidade (100%). Portanto, s&#xF3; a avalia&#xE7;&#xE3;o hemodin&#xE2;mica invasiva em repouso e no esfor&#xE7;o &#xE9; capaz de definitivamente confirmar ou refutar o diagn&#xF3;stico de ICFEP.<sup><xref ref-type="bibr" rid="B22">22</xref>&#x2013;<xref ref-type="bibr" rid="B26">26</xref></sup></p>
<p>Al&#xE9;m do diagn&#xF3;stico precoce, a avalia&#xE7;&#xE3;o hemodin&#xE2;mica invasiva traz importantes informa&#xE7;&#xF5;es sobre a gravidade e progn&#xF3;stico da ICFEP. A press&#xE3;o capilar pulmonar elevada durante o esfor&#xE7;o e a rela&#xE7;&#xE3;o da press&#xE3;o capilar pulmonar/d&#xE9;bito c&#xE1;rdico est&#xE3;o relacionadas a um pior progn&#xF3;stico a curto e m&#xE9;dio prazo.<sup><xref ref-type="bibr" rid="B27">27</xref>,<xref ref-type="bibr" rid="B28">28</xref></sup></p>
<p>A avalia&#xE7;&#xE3;o hemodin&#xE2;mica invasiva em repouso &#xE9; &#xFA;til em casos de anormalidades hemodin&#xE2;micas como eleva&#xE7;&#xF5;es nas press&#xF5;es de enchimento. Por&#xE9;m, em press&#xF5;es de enchimento normais, as quais n&#xE3;o afastam o diagn&#xF3;stico de ICFEP, tem limitada sensibilidade tendo visto que nessa condi&#xE7;&#xE3;o as press&#xF5;es de enchimento s&#xF3; se elevam com o esfor&#xE7;o.<sup><xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup> Portanto, a avalia&#xE7;&#xE3;o hemodin&#xE2;mica invasiva com esfor&#xE7;o &#xE9; que permite diagnosticar ou afastar a ICFEP como causa da dispneia, uma vez que tem sensibilidade e especificidade de 100%.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B23">23</xref></sup> Alternativas como sobrecarga aguda de volume ou eleva&#xE7;&#xE3;o dos membros inferiores (leg raise) para aumentar o retorno venoso tem algum valor, contudo n&#xE3;o devem substituir a avalia&#xE7;&#xE3;o hemodin&#xE2;mica com o exerc&#xED;cio; essas estrat&#xE9;gias adicionais ficam reservadas para os pacientes que n&#xE3;o podem realizar o exerc&#xED;cio com os membros inferiores ou quando o paciente se encontra desidratado nas medidas press&#xF3;ricas de repouso.<sup><xref ref-type="bibr" rid="B29">29</xref>,<xref ref-type="bibr" rid="B30">30</xref></sup></p>
</sec>
<sec>
<title>Indica&#xE7;&#xF5;es da AHI na ICFEP</title>
<p>O manejo de todos os pacientes com a s&#xED;ndrome de ICFEP, pacientes idosos com hipertens&#xE3;o pulmonar inexplicada, e pacientes com dispneia inexplicada devem seguir os fluxogramas para ICFEP que incluem a aplica&#xE7;&#xE3;o dos escores diagn&#xF3;sticos e par&#xE2;metros de avalia&#xE7;&#xE3;o da fun&#xE7;&#xE3;o diast&#xF3;lica pela ecocardiografia em repouso ou com stress diast&#xF3;lico.<sup><xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B23">23</xref></sup> Nos diferentes, estudos cerca de 50% dos pacientes com escore de risco intermedi&#xE1;rio podem ter ICEFEP n&#xE3;o diagnosticada sem a realiza&#xE7;&#xE3;o da AHI com esfor&#xE7;o.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup> Na sequ&#xEA;ncia est&#xE3;o as principais indica&#xE7;&#xF5;es da AHI (<xref ref-type="table" rid="t5">Tabela 2</xref>).</p>
<table-wrap id="t5">
<label>Tabela 2</label>
<caption><title>Principais indica&#xE7;&#xF5;es da Avalia&#xE7;&#xE3;o Hemodin&#xE2;mica Invasiva</title></caption>
<table frame="hsides" rules="rows">
<colgroup width="50%">
<col/>
<col/>
</colgroup>
<tbody style="border-bottom: thin solid; border-color: #000000">
<tr>
<td align="left" valign="middle">1</td>
<td align="left" valign="middle">Pacientes com janela ecocardiogr&#xE1;fica inadequada para avalia&#xE7;&#xE3;o da fun&#xE7;&#xE3;o diast&#xF3;lica pelo ecocardiograma de repouso.</td>
</tr>
<tr>
<td align="left" valign="middle">2</td>
<td align="left" valign="middle">Incapacidade de obter par&#xE2;metros confi&#xE1;veis no ecocardiograma de esfor&#xE7;o.</td>
</tr>
<tr>
<td align="left" valign="middle">3</td>
<td align="left" valign="middle">Pacientes em ritmo de fibrila&#xE7;&#xE3;o atrial permanente.</td>
</tr>
<tr>
<td align="left" valign="middle">4</td>
<td align="left" valign="middle">Pacientes com escore H2FPEF com risco intermedi&#xE1;rio (4-8 pontos).</td>
</tr>
<tr>
<td align="left" valign="middle">5</td>
<td align="left" valign="middle">Pacientes com o par&#xE2;metro ecocardiogr&#xE1;fico E/e&#xB4; entre 9 e 15.</td>
</tr>
<tr>
<td align="left" valign="middle">6</td>
<td align="left" valign="middle">Pacientes com doen&#xE7;a pulmonar ou doen&#xE7;a mista como DPOC que pode ser respons&#xE1;vel pela dispneia</td>
</tr>
<tr>
<td align="left" valign="middle">7</td>
<td align="left" valign="middle">Dispneia e/ou hipertens&#xE3;o pulmonar a esclarecer.</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TFN5"><p>DPOC: doen&#xE7;a pulmonar obstrutiva cr&#xF4;nica</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec>
<title>Protocolo do estudo hemodin&#xE2;mico invasivo na ICFEP</title>
<p>N&#xF3;s adotamos e recomendamos o protocolo de avalia&#xE7;&#xE3;o proposto por Borlaug et al.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup> (<xref ref-type="table" rid="t6">Tabela 3</xref>). &#xC9; recomend&#xE1;vel que o paciente receba previamente um breve treinamento para fazer exerc&#xED;cio com o ciclo ergom&#xE9;trico no leito na posi&#xE7;&#xE3;o supina, pois favorece o retorno venoso e maximiza a eleva&#xE7;&#xE3;o da press&#xE3;o capilar pulmonar (<xref ref-type="fig" rid="f4">Figura 1</xref>). Quando o paciente &#xE9; muito obeso e n&#xE3;o tolera a posi&#xE7;&#xE3;o supina, recomenda-se a eleva&#xE7;&#xE3;o do dec&#xFA;bito a no m&#xE1;ximo 45 graus. Ambas as situa&#xE7;&#xF5;es devem ser realizadas sob a monitoriza&#xE7;&#xE3;o cont&#xED;nua eletrocardiogr&#xE1;fica e oximetria digital, com o paciente respirando em ar ambiente. Para os pacientes com fibrila&#xE7;&#xE3;o atrial &#xE9; recomend&#xE1;vel um bom controle de frequ&#xEA;ncia card&#xED;aca antes da avalia&#xE7;&#xE3;o hemodin&#xE2;mica invasiva. Ressaltamos que o paciente n&#xE3;o deve estar desidratado por excesso de diur&#xE9;tico.</p>
<table-wrap id="t6">
<label>Tabela 3</label>
<caption><title>Passos da Avalia&#xE7;&#xE3;o Hemodin&#xE2;mica Invasiva no diagn&#xF3;stico de insufici&#xEA;ncia card&#xED;aca com fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o preservada</title></caption>
<table frame="hsides" rules="rows">
<colgroup width="50%">
<col/>
<col/>
</colgroup>
<tbody style="border-bottom: thin solid; border-color: #000000">
<tr>
<td align="left" valign="middle">1</td>
<td align="left" valign="middle">Pun&#xE7;&#xE3;o da veia jugular direita e coloca&#xE7;&#xE3;o de um introdutor 8F para a cateterismo da circula&#xE7;&#xE3;o pulmonar com cateter de Swan-Ganz</td>
</tr>
<tr>
<td align="left" valign="middle">2</td>
<td align="left" valign="middle">Pun&#xE7;&#xE3;o da art&#xE9;ria radial direita ou esquerda com introdutor 5F para cateterismo da cavidade ventricular esquerda com cateter pigtail 5F e medida da press&#xE3;o arterial e da press&#xE3;o diast&#xF3;lica final do ventr&#xED;culo esquerdo.</td>
</tr>
<tr>
<td align="left" valign="middle">3</td>
<td align="left" valign="middle">Posicionar o cateter de Swan-Ganz na zona 2 do pulm&#xE3;o para obten&#xE7;&#xE3;o da press&#xE3;o capilar pulmonar encunhada (curva press&#xF3;rica capilar t&#xED;pica).</td>
</tr>
<tr>
<td align="left" valign="middle">4</td>
<td align="left" valign="middle">Instalar os transdutores de press&#xE3;o com o &#x201C;zero&#x201D; a n&#xED;vel da linha axilar m&#xE9;dia para as medidas das press&#xF5;es em &#xE1;trio direito, ventr&#xED;culo direito e na art&#xE9;ria pulmonar, press&#xE3;o capilar pulmonar, press&#xE3;o diast&#xF3;lica final do ventr&#xED;culo esquerdo e press&#xE3;o arterial m&#xE9;dia. Medidas conforme as fases do ciclo card&#xED;aco (ao final da di&#xE1;stole ventricular) e se poss&#xED;vel no final da expira&#xE7;&#xE3;o.</td>
</tr>
<tr>
<td align="left" valign="middle">5</td>
<td align="left" valign="middle">Obter as medidas press&#xF3;ricas e d&#xE9;bito card&#xED;aco basais em repouso. Nos pacientes com fibrila&#xE7;&#xE3;o atrial, obter medidas press&#xF3;ricas m&#xE9;dia durante 10 batimentos card&#xED;acos consecutivos. As medidas s&#xE3;o capturadas em pol&#xED;grafo de hemodin&#xE2;mica e impressas em impressora acoplada.</td>
</tr>
<tr>
<td align="left" valign="middle">6</td>
<td align="left" valign="middle">Ajustar os p&#xE9;s do paciente nos pedais do ciclo ergom&#xE9;trico e fix&#xE1;-los com faixa adesiva.</td>
</tr>
<tr>
<td align="left" valign="middle">7</td>
<td align="left" valign="middle">Iniciar o protocolo de exerc&#xED;cio com carga de 20 Watts e 60 rota&#xE7;&#xF5;es por minuto (rpm) por tr&#xEA;s minutos e, em seguida, avan&#xE7;ar para o est&#xE1;gio seguinte com carga de 40 Watts por mais tr&#xEA;s minutos. No pico do esfor&#xE7;o ou no m&#xE1;ximo da toler&#xE2;ncia do paciente, realizar medidas press&#xF3;ricas e do d&#xE9;bito card&#xED;aco.</td>
</tr>
<tr>
<td align="left" valign="middle">8</td>
<td align="left" valign="middle">Ap&#xF3;s cinco minutos de repouso, realizar novamente todas as medidas press&#xF3;ricas.</td>
</tr>
<tr>
<td align="left" valign="middle">9</td>
<td align="left" valign="middle">Como a maioria dos pacientes tem fatores de risco para doen&#xE7;a coronariana, realizar cinecoronariografia diagn&#xF3;stica antes de retirar a linha radial.</td>
</tr>
<tr>
<td align="left" valign="middle">10</td>
<td align="left" valign="middle">Ap&#xF3;s o t&#xE9;rmino do exame, analisamos as curvas press&#xF3;ricas e medidas de d&#xE9;bito card&#xED;aco, calculamos as resist&#xEA;ncias vascular pulmonar e sist&#xEA;mica, medimos o gradiente transpulmonar e o gradiente diast&#xF3;lico pulmonar e eventual gradiente capilar/press&#xE3;o diast&#xF3;lica final do ventr&#xED;culo esquerdo.</td>
</tr>
<tr>
<td align="left" valign="middle">11</td>
<td align="left" valign="middle">Para o diagn&#xF3;stico de ICFEP considera-se medida de press&#xE3;o capilar pulmonar ou press&#xE3;o diast&#xF3;lica final do ventr&#xED;culo esquerdo em repouso &#x2265; que 15 mmHg e &#x2265; que 25 mmHg no esfor&#xE7;o.</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TFN6"><p>ICFEP: insufici&#xEA;ncia card&#xED;aca com fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o preservada.</p></fn>
</table-wrap-foot>
</table-wrap>
<fig id="f4">
<label>Figura 1</label>
<caption><title>Simula&#xE7;&#xE3;o da posi&#xE7;&#xE3;o do paciente na mesa de hemodin&#xE2;mica para avalia&#xE7;&#xE3;o hemodin&#xE2;mica invasiva com esfor&#xE7;o para diagn&#xF3;stico de ICFEP.</title></caption>
<graphic xlink:href="2764-3107-abchf-002-03-0290-gf01-pt.tif"/>
</fig>
<p>A seguir, descrevemos a sequ&#xEA;ncia na qual a AHI deve ser realizada para o diagn&#xF3;stico da ICFEP. O protocolo recomenda iniciar o exame com carga de 20 watts por tr&#xEA;s minutos (primeiro est&#xE1;gio) seguindo 40 watts por mais tr&#xEA;s minutos (segundo est&#xE1;gio). Os estudos demonstram que, na maioria dos pacientes com ICEP, as press&#xF5;es de enchimento j&#xE1; se elevam para n&#xED;veis anormais no final do primeiro est&#xE1;gio<sup><xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref></sup> e voltam rapidamente ao valor basal ap&#xF3;s a interrup&#xE7;&#xE3;o do esfor&#xE7;o (<xref ref-type="fig" rid="f5">Figura 2</xref>).<sup><xref ref-type="bibr" rid="B31">31</xref>&#x2013;<xref ref-type="bibr" rid="B33">33</xref></sup></p>
<fig id="f5">
<label>Figura 2</label>
<caption><title>Magnitude temporal da eleva&#xE7;&#xE3;o das press&#xF5;es capilar pulmonar e diast&#xF3;lica final do ventr&#xED;culo esquerdo durante o esfor&#xE7;o em indiv&#xED;duos normais e em pacientes com ICFEP Obokata et al Circulation 2017; 135:825-38 (Autorizado pelo autor). PDFVE: press&#xE3;o diast&#xF3;lica final do ventr&#xED;culo esquerdo; ICFEP: insufici&#xEA;ncia card&#xED;aca com fra&#xE7;&#xE3;o de eje&#xE7;&#xE3;o preservada; PA: press&#xE3;o arterial; NCD: dispneia n&#xE3;o card&#xED;aca.</title></caption>
<graphic xlink:href="2764-3107-abchf-002-03-0290-gf02-pt.tif"/>
</fig>
</sec>
<sec>
<title>Interpreta&#xE7;&#xE3;o do estudo hemodin&#xE2;mico invasivo</title>
<p>A interpreta&#xE7;&#xE3;o adequada dos resultados do estudo hemodin&#xE2;mico invasivo requer a obten&#xE7;&#xE3;o de curvas de press&#xE3;o de enchimento, press&#xE3;o em cavidades direitas, press&#xE3;o pulmonar, e press&#xE3;o diast&#xF3;lica final do VE de alta qualidade, obtidas de prefer&#xEA;ncia no final da expira&#xE7;&#xE3;o em repouso e no pico do esfor&#xE7;o (<xref ref-type="fig" rid="f6">Figura 3</xref>).</p>
<fig id="f6">
<label>Figura 3</label>
<caption><title>Representa&#xE7;&#xE3;o das curvas de press&#xE3;o capilar pulmonar (PCWP) e press&#xE3;o diast&#xF3;lica final do ventr&#xED;culo esquerdo (PDFVE) em repouso e no pico do esfor&#xE7;o em paciente com ICFEP. (Adaptado de Circ Heart Fail. 2010;3:588-595).</title></caption>
<graphic xlink:href="2764-3107-abchf-002-03-0290-gf03-pt.tif"/>
</fig>
<p>A an&#xE1;lise integrada de todos os par&#xE2;metros hemodin&#xE2;micos obtidos no repouso e no esfor&#xE7;o ir&#xE3;o permitir o correto diagn&#xF3;stico ou a exclus&#xE3;o da ICFEP como causa dos sintomas dos pacientes. Nos casos em que as curvas de press&#xE3;o capilar pulmonar n&#xE3;o sejam de &#xF3;tima qualidade, a obten&#xE7;&#xE3;o da PD2 do VE simultaneamente substitui a press&#xE3;o capilar, essa medida deve ser preferida principalmente nos casos de fibrila&#xE7;&#xE3;o atrial ou quando a curva capilar pulmonar possa estar contaminada pela presen&#xE7;a de onda V decorrente de insufici&#xEA;ncia mitral. O diagn&#xF3;stico de ICFEP &#xE9; estabelecido quando a press&#xE3;o capilar pulmonar &#xE9; igual ou superior a 15 mmHg em repouso ou igual ou superior a 25 mmHg no esfor&#xE7;o.<sup><xref ref-type="bibr" rid="B22">22</xref>&#x2013;<xref ref-type="bibr" rid="B24">24</xref>,<xref ref-type="bibr" rid="B34">34</xref></sup> Na presen&#xE7;a de fibrila&#xE7;&#xE3;o atrial devemos utilizar a m&#xE9;dia de press&#xE3;o obtida em 10 ciclos card&#xED;acos consecutivos e n&#xE3;o devemos considerar medidas de batimentos extras sist&#xF3;licos. Cabe ressaltar que as medidas press&#xF3;ricas normais em repouso n&#xE3;o afastam o diagn&#xF3;stico de ICFEP, sendo mandat&#xF3;rio repetir as medidas com esfor&#xE7;o.<sup><xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B33">33</xref>,<xref ref-type="bibr" rid="B35">35</xref></sup> Caso o paciente n&#xE3;o consiga exercitar as pernas, podemos lan&#xE7;ar m&#xE3;o de exerc&#xED;cio de bra&#xE7;o ou teste de sobrecarga vol&#xEA;mica ou a manobra de eleva&#xE7;&#xE3;o passiva dos membros inferiores ou at&#xE9; mesmos a associa&#xE7;&#xE3;o das duas manobras.<sup><xref ref-type="bibr" rid="B29">29</xref>,<xref ref-type="bibr" rid="B30">30</xref>,<xref ref-type="bibr" rid="B35">35</xref>,<xref ref-type="bibr" rid="B36">36</xref></sup></p>
<p>Em conclus&#xE3;o, devido &#xE0;s dificuldades acerca do correto diagn&#xF3;stico de ICFEP pela baixa sensibilidade e especificidade dos m&#xE9;todos de avalia&#xE7;&#xE3;o n&#xE3;o invasiva, principalmente aquelas obtidas em repouso, o estudo hemodin&#xE2;mico invasivo com esfor&#xE7;o emerge como o m&#xE9;todo gold standard para diagn&#xF3;stico de ICFEP devido a objetividade das medidas das press&#xF5;es de enchimento e taxas elevadas de sensibilidade e especificidade com valores preditivos positivo e negativo de praticamente 100%.<sup><xref ref-type="bibr" rid="B32">32</xref>,<xref ref-type="bibr" rid="B33">33</xref></sup> Ressaltamos que o exame &#xE9; seguro e pode ser empregado na maioria dos pacientes com fen&#xF3;tipo de ICFEP, sobretudo nos casos que apresentam escore de risco intermedi&#xE1;rio, em pacientes com dispneia a esclarecer e em pacientes com hipertens&#xE3;o pulmonar de causa n&#xE3;o explicada ap&#xF3;s a realiza&#xE7;&#xE3;o dos exames n&#xE3;o invasivos.<sup><xref ref-type="bibr" rid="B23">23</xref>&#x2013;<xref ref-type="bibr" rid="B25">25</xref></sup></p>
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<fn-group>
<fn fn-type="supported-by" id="fn4"><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="fn5">
<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 fn-type="other" id="fn6">
<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>
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