<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "https://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article article-type="research-article" dtd-version="1.1" specific-use="sps-1.9" xml:lang="en" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">
	<front>
		<journal-meta>
			<journal-id journal-id-type="nlm-ta">abchf</journal-id>
			<journal-id journal-id-type="publisher-id">abchf</journal-id>
			<journal-title-group>
				<journal-title>ABC Heart Fail Cardiomyop</journal-title>
				<abbrev-journal-title abbrev-type="publisher">ABC Heart Fail Cardiomyop</abbrev-journal-title>
			</journal-title-group>
			<issn pub-type="ppub">2764-3107</issn>
			<publisher>
				<publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
			</publisher>
		</journal-meta>
		<article-meta>
			<article-id pub-id-type="doi">10.36660/abchf.20250027i</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Original Article</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Analysis of the Clinical and Epidemiological Profile of Patients with Heart Failure with Reduced Ejection Fraction in a Hospital in Southern Santa Catarina</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0007-0473-8706</contrib-id>
					<name>
						<surname>Borges</surname>
						<given-names>Gabriela Aline</given-names>
					</name>
					<role>Conception and design of the research</role>
					<role>Analysis and interpretation of the data and Critical revision of the manuscript for intellectual content</role>
					<role>Acquisition of data</role>
					<role>Statistical analysis and Writing of the manuscript</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0005-8241-8447</contrib-id>
					<name>
						<surname>Luca</surname>
						<given-names>Mateus De</given-names>
					</name>
					<role>Conception and design of the research</role>
					<role>Analysis and interpretation of the data and Critical revision of the manuscript for intellectual content</role>
					<role>Acquisition of data</role>
					<role>Statistical analysis and Writing of the manuscript</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0001-1840-3938</contrib-id>
					<name>
						<surname>Bolan</surname>
						<given-names>Amanda Cirimbelli</given-names>
					</name>
					<role>Conception and design of the research</role>
					<role>Analysis and interpretation of the data and Critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff1">
				<label>1</label>
				<institution content-type="orgname">Universidade do Extremo Sul Catarinense</institution>
				<addr-line>
					<named-content content-type="city">Criciúma</named-content>
					<named-content content-type="state">SC</named-content>
				</addr-line>
				<country country="BR">Brazil</country>
				<institution content-type="original">Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC – Brazil</institution>
			</aff>
			<author-notes>
				<corresp id="c01">
					<label>Mailing Address:</label> Gabriela Aline Borges Universidade do Extremo Sul Catarinense (UNESC) - Av. Universitária, 1105. Postal Code 88806-000, Criciúma, SC - Brazil E-mail: <email>gabriela.abo@gmail.com</email>
				</corresp>
				<fn fn-type="coi-statement">
					<label>Potential Conflict of Interest:</label>
					<p>No potential conflict of interest relevant to this article was reported.</p>
				</fn>
				<fn fn-type="edited-by">
					<label>Editor responsible for the review:</label>
					<p>Humberto Villacorta</p>
				</fn>
			</author-notes>
			<pub-date date-type="pub" publication-format="electronic">
				<day>31</day>
				<month>12</month>
				<year>2025</year>
			</pub-date>
			<pub-date date-type="collection" publication-format="electronic">
				<month>12</month>
				<year>2025</year>
			</pub-date>
			<volume>5</volume>
			<issue>3</issue>
			<elocation-id>e20250027</elocation-id>
			<history>
				<date date-type="received">
					<day>09</day>
					<month>10</month>
					<year>2025</year>
				</date>
				<date date-type="rev-recd">
					<day>30</day>
					<month>01</month>
					<year>2026</year>
				</date>
				<date date-type="accepted">
					<day>26</day>
					<month>02</month>
					<year>2026</year>
				</date>
			</history>
			<permissions>
				<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
					<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License.</license-p>
				</license>
			</permissions>
			<abstract>
				<title>Abstract</title>
				<sec>
					<title>Background</title>
					<p> Heart failure with reduced ejection fraction (HFrEF) accounts for approximately half of all heart failure hospitalizations, negatively impacts patients’ functional capacity and quality of life, and is associated with high financial costs in health care.</p>
				</sec>
				<sec>
					<title>Objectives</title>
					<p> To analyze the clinical and epidemiological profile of patients with heart failure with HFrEF in a hospital in southern Santa Catarina in the year 2023.</p>
				</sec>
				<sec>
					<title>Methods</title>
					<p> 147 patients with HFrEF were evaluated in a reference hospital in southern Santa Catarina. The data were collected through electronic medical records from which information such as left ventricular ejection fraction (LVEF), sex, age, race/color, weight, height, medications in use, and associated conditions was extracted.</p>
				</sec>
				<sec>
					<title>Results</title>
					<p> The mean age of the study population was 68.14 ± 12.88 years. Males represented 57.8% of the patients, and 88.4% were white. Of the total, 25.5% presented some degree of obesity. Systemic arterial hypertension was observed in 68.7%, diabetes mellitus in 56.5%, and ischemic cardiomyopathies in 31.3% of the individuals. The mean LVEF value was 28.54 ± 6.72%. The recommended triple pharmacological therapy was present in 45.6% of the individuals, while the association with iSGLT2 was observed in 34.8%.</p>
				</sec>
				<sec>
					<title>Conclusions</title>
					<p> It was possible to identify the clinical and epidemiological profile of the study population and, above all, to highlight that more than half of this population was not using optimized drug therapy. Therefore, the importance of clinical and epidemiological data for reviewing and optimizing patient management is emphasized.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="en">
				<title>Keywords:</title>
				<kwd>Systolic Heart Failure</kwd>
				<kwd>Clinical Epidemiology</kwd>
				<kwd>Clinical Medicine</kwd>
			</kwd-group>
			<funding-group>
				<funding-statement><bold>Sources of Funding:</bold> There were no external funding sources for this study.</funding-statement>
			</funding-group>
			<counts>
				<fig-count count="2"/>
				<table-count count="4"/>
				<equation-count count="0"/>
				<ref-count count="46"/>
			</counts>
		</article-meta>
	</front>
	<body>
		<sec sec-type="intro">
			<title>Introduction</title>
			<p>Heart failure (HF) has been identified as a major public health problem and considered a new epidemic, with high mortality and morbidity, despite advances in current therapies.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup> In Brazil, data from the I Brazilian Registry of Acute Heart Failure show that HF is one of the main causes of hospital readmission<sup><xref ref-type="bibr" rid="B1">1</xref></sup>. In this sense, attempts to reduce its social burden, in the clinical and economic spheres, have become an important global public health priority.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
			<p>A wide range of heart conditions, hereditary defects, and systemic diseases can result in heart failure, most notably ischemic heart disease and hypertensive heart disease. congenital heart disease, dyslipidemia, and diabetes.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup> Additionally, Advanced age, male sex,<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> sedentary lifestyle, and smoking are important factors associated with heart failure, and the estimated contribution of each of these risk factors may vary over time and by race and ethnicity.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup></p>
			<p>To aid in better management, patients with HF can be classified according to several aspects. Differentiating patients according to left ventricular ejection fraction (LVEF) is of great importance, since they differ in relation to the main etiologies, associated comorbidities, and, especially, the response to therapy.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Heart failure with reduced ejection fraction (HFrEF) is defined as LVEF &lt;40% and negatively impacts patients’ functional capacity and quality of life, as well as healthcare costs. However, despite investments in improving the management of HFrEF, this condition is still associated with high hospitalization and mortality rates.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup></p>
			<p>In this context, continuous evaluation of the epidemiology of HFrEF is necessary to provide a scientific basis for the rational allocation of health resources and for the development of strategies aimed at reducing the impacts of this condition.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> However, in Brazil, there are few studies that comprehensively and prospectively evaluate the demographic, clinical, and prognostic characteristics of patients admitted with a clinical diagnosis of HF.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
			<p>Considering the functional and economic impacts of HFrEF and the scarcity of studies on this topic in Brazil, research is needed to contribute to the epidemiological knowledge and the demographic and clinical characterization of this population. Therefore, the objective of this study was to analyze the clinical and epidemiological profile of patients with HFrEF in a hospital in southern Santa Catarina.</p>
		</sec>
		<sec sec-type="materials|methods">
			<title>Materials and methods</title>
			<sec>
				<title>Ethical aspects</title>
				<p>This study was approved by the Research and Human Ethics Committee of the educational institution, through opinion number 6.582.013, and by the Research Ethics Committee of the hospital where the study was conducted, through opinion number 6.705.122.</p>
			</sec>
			<sec>
				<title>Study Design</title>
				<p>This is a descriptive observational study, with secondary data collection and a quantitative approach.</p>
			</sec>
			<sec>
				<title>Population</title>
				<p>One hundred and forty-seven patients with HFrEF at a hospital in southern Santa Catarina were analyzed between January and December 2023. For initial patient selection, the ICD-10 classification corresponding to HF (I50, I50.0, I50.1, and I50.9) recorded in the medical records was used. Subsequently, echocardiography was considered, using the Teichholz or Simpson methods, for HF classification according to LVEF. <xref ref-type="fig" rid="f01">Figure 1</xref> illustrates the sample selection flowchart for the study.</p>
				<p>
					<fig id="f01">
						<label>Figure 1</label>
						<caption>
							<title>– Flowchart of the study sample selection. HF: Heart Failure; LVEF: Left Ventricular Ejection Fraction; HFrEF: Heart Failure with Reduced Ejection Fraction. Source: Prepared by the authors.</title>
						</caption>
						<graphic xlink:href="2764-3107-abchf-5-3-e20250027-gf01.tif"/>
					</fig>
				</p>
			</sec>
			<sec>
				<title>Exclusion criteria</title>
				<p>There were no exclusions in this study.</p>
			</sec>
			<sec>
				<title>Data collected</title>
				<p>Patients were evaluated using electronic medical records, from which the following information was extracted: LVEF (obtained through echocardiographic examination), sex, age, race/color, height, weight, body mass index (BMI), medications in use, and associated comorbidities.</p>
			</sec>
			<sec>
				<title>Data analysis</title>
				<p>The collected data were analyzed using IBM Statistical Package for the Social Sciences (SPSS) software, version 23.0. The variables age (years) and LVEF (%) were expressed as mean and standard deviation. The qualitative variables (sex, race/color, medications in use, and comorbidities) were expressed as frequency and percentage.</p>
			</sec>
		</sec>
		<sec sec-type="results">
			<title>Results</title>
			<p>The Central Figure illustrates the main findings of the research. <xref ref-type="table" rid="t1">Table 1</xref> shows the clinical and epidemiological profile of the study population. The mean age was 68.14 ± 12.88 years, and males represented 57.8% of the patients. Regarding race/color, white corresponded to 88.4%. As for BMI, 43.4% had adequate weight, 29.7% were overweight, and 25.5% presented some degree of obesity. Among the comorbidities, systemic arterial hypertension was present in 68.7% of the patients, diabetes mellitus in 56.5%, and ischemic cardiomyopathy in 31.3% of the study population. Beta-blockers were the medications used by 81.0% of the patients, followed by diuretics (70.1%) and ACEis/ARBs, used by 65.3%. The LVEF had a mean of 28.54 ± 6.72%. Of the 147 patients analyzed, 19 died during the same hospitalization.</p>
			<p>
				<table-wrap id="t1">
					<label>Table 1</label>
					<caption>
						<title>– Clinical and epidemiological profile of patients diagnosed with heart failure with reduced ejection fraction treated at a high-complexity hospital in southern Santa Catarina in 2023</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup>
							<col/>
							<col/>
						</colgroup>
						<thead>
							<tr>
								<th align="left" style="font-weight:normal"> </th>
								<th>Mean ± SD, n (%)</th>
							</tr>
						</thead>
						<tbody>
							<tr>
								<td> </td>
								<td align="center"><bold>n = 147</bold></td>
							</tr>
							<tr>
								<td><bold>Age (years)</bold></td>
								<td align="center">68.14 ± 12.88</td>
							</tr>
							<tr>
								<td><bold>Sex</bold></td>
								<td> </td>
							</tr>
							<tr>
								<td>Masculine</td>
								<td align="center">85 (57.8)</td>
							</tr>
							<tr>
								<td>Feminine</td>
								<td align="center">62 (42.2)</td>
							</tr>
							<tr>
								<td><bold>Race/Color</bold></td>
								<td> </td>
							</tr>
							<tr>
								<td>White</td>
								<td align="center">130 (88.4)</td>
							</tr>
							<tr>
								<td>Black</td>
								<td align="center">15 (10.2)</td>
							</tr>
							<tr>
								<td>Brown</td>
								<td align="center">2 (1.4)</td>
							</tr>
							<tr>
								<td><bold>Body mass index</bold></td>
								<td> </td>
							</tr>
							<tr>
								<td>Underweight</td>
								<td align="center">2 (1.4)</td>
							</tr>
							<tr>
								<td>Appropriate weight</td>
								<td align="center">63 (43.4)</td>
							</tr>
							<tr>
								<td>Overweight</td>
								<td align="center">43 (29.7)</td>
							</tr>
							<tr>
								<td>Grade I obesity</td>
								<td align="center">27 (18.6)</td>
							</tr>
							<tr>
								<td>Grade II obesity</td>
								<td align="center">8 (5.5)</td>
							</tr>
							<tr>
								<td>Grade III obesity</td>
								<td align="center">2 (1.4)</td>
							</tr>
							<tr>
								<td>No information</td>
								<td align="center">2</td>
							</tr>
							<tr>
								<td><bold>Comorbidities</bold></td>
								<td> </td>
							</tr>
							<tr>
								<td>Systemic arterial hypertension</td>
								<td align="center">101 (68.7)</td>
							</tr>
							<tr>
								<td>Diabetes mellitus</td>
								<td align="center">83 (56.5)</td>
							</tr>
							<tr>
								<td>Ischemic heart disease</td>
								<td align="center">46 (31.3)</td>
							</tr>
							<tr>
								<td>Obesity</td>
								<td align="center">37 (25.2)</td>
							</tr>
							<tr>
								<td>Smoking</td>
								<td align="center">32 (21.8)</td>
							</tr>
							<tr>
								<td>No comorbidities reported.</td>
								<td align="center">6 (4.1)</td>
							</tr>
							<tr>
								<td><bold>Medications in use</bold></td>
								<td> </td>
							</tr>
							<tr>
								<td>Beta blocker</td>
								<td align="center">119 (81.0)</td>
							</tr>
							<tr>
								<td>Diuretic</td>
								<td align="center">103 (70.1)</td>
							</tr>
							<tr>
								<td>ACEi/ARB</td>
								<td align="center">96 (65.3)</td>
							</tr>
							<tr>
								<td>Mineralocorticoid antagonist</td>
								<td align="center">87 (59.2)</td>
							</tr>
							<tr>
								<td>iSGLT2</td>
								<td align="center">83 (56.5)</td>
							</tr>
							<tr>
								<td>ARNi</td>
								<td align="center">20 (13.6)</td>
							</tr>
							<tr>
								<td>LVEF (%)</td>
								<td align="center">28.54 ± 6.72</td>
							</tr>
							<tr>
								<td><bold>Death</bold></td>
								<td align="center">19 (12.9)</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN1">
							<p>ACEi/ARB: angiotensin-converting enzyme inhibitor/Angiotensin receptor blocker; iSGLT2: sodium/glucose cotransporter type 2 inhibitor; ARNi: neprilysin inhibitor; Diuretic: loop diuretic; LVEF: left ventricular ejection fraction. Source: Research data, 2024.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
			</p>
			<p>
				<xref ref-type="table" rid="t2">Table 2</xref> shows the medications used by patients diagnosed with HFrEF. Regarding therapeutic combinations, 29.2% of patients used four medications, 25.2% used five medications, 22.4% used three medications, and 13.6% used two medications. Only nine patients (6.1%) used one medication, and five (3.4%) did not use any medication. In the combinatorial analysis of drugs, considering the use of only one medication, diuretics were used by 2.7% of patients. The combination of diuretics with beta-blockers was observed in 4.8% of patients, and the combination of these two drugs with ACEis/ARBs was present in 6.1%. Among patients using four medications, the combination of beta-blockers, ACEis/ARBs, mineralocorticoid antagonists, and iSGLT2 accounted for 8.2%. Twenty-seven patients (18.4%) were identified as using a combination of beta-blocker, ACEi/ARB, mineralocorticoid antagonist, iSGLT2, and diuretic.</p>
			<p>
				<table-wrap id="t2">
					<label>Table 2</label>
					<caption>
						<title>– Combination of medications for patients diagnosed with heart failure with reduced ejection fraction treated at a high-complexity hospital in southern Santa Catarina in 2023</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup>
							<col/>
							<col/>
						</colgroup>
						<thead>
							<tr>
								<th align="left" style="font-weight:normal"> </th>
								<th>n (%)</th>
							</tr>
						</thead>
						<tbody>
							<tr>
								<td> </td>
								<td align="center"><bold>n = 147</bold></td>
							</tr>
							<tr>
								<td><bold>Combination of medications</bold></td>
								<td> </td>
							</tr>
							<tr>
								<td><bold>No medication</bold></td>
								<td align="center"><bold>5 (3.4)</bold></td>
							</tr>
							<tr>
								<td><bold>Only 1 medication</bold></td>
								<td align="center"><bold>9 (6.1)</bold></td>
							</tr>
							<tr>
								<td>Diuretic</td>
								<td align="center">4 (2.7)</td>
							</tr>
							<tr>
								<td>ACEi/ARB</td>
								<td align="center">2 (1.4)</td>
							</tr>
							<tr>
								<td>ARNi</td>
								<td align="center">2 (1.4)</td>
							</tr>
							<tr>
								<td>Beta blocker</td>
								<td align="center">1 (0.7)</td>
							</tr>
							<tr>
								<td><bold>2 medications</bold></td>
								<td align="center"><bold>20 (13.6)</bold></td>
							</tr>
							<tr>
								<td>Beta-blocker, Diuretic</td>
								<td align="center">7 (4.8)</td>
							</tr>
							<tr>
								<td>ACEi/ARB, Diuretic</td>
								<td align="center">6 (4.1)</td>
							</tr>
							<tr>
								<td>Beta-blocker, ACEi/ARB</td>
								<td align="center">4 (2.7)</td>
							</tr>
							<tr>
								<td>Beta blocker, iSGLT2</td>
								<td align="center">1 (0.7)</td>
							</tr>
							<tr>
								<td>Mineralocorticoid antagonist, Diuretic</td>
								<td align="center">1 (0.7)</td>
							</tr>
							<tr>
								<td>iSGLT2, Diuretic</td>
								<td align="center">1 (0.7)</td>
							</tr>
							<tr>
								<td><bold>3 medications</bold></td>
								<td align="center"><bold>33 (22.4)</bold></td>
							</tr>
							<tr>
								<td>Beta blocker, ACEi/ARB, Diuretic</td>
								<td align="center">9 (6.1)</td>
							</tr>
							<tr>
								<td>Beta blocker, Mineralocorticoid antagonist, Diuretic</td>
								<td align="center">7 (4.8)</td>
							</tr>
							<tr>
								<td>Beta blocker, ACEi/ARB, iSGLT2</td>
								<td align="center">5 (3.4)</td>
							</tr>
							<tr>
								<td>Beta blocker, ACEi/ARB, Mineralocorticoid antagonist</td>
								<td align="center">4 (2.7)</td>
							</tr>
							<tr>
								<td>Beta blocker, Mineralocorticoid antagonist, iSGLT2</td>
								<td align="center">2 (1.4)</td>
							</tr>
							<tr>
								<td>Mineralocorticoid Antagonist, iSGLT2, Diuretic</td>
								<td align="center">2 (1.4)</td>
							</tr>
							<tr>
								<td>Beta blocker, Mineralocorticoid antagonist, ARNi</td>
								<td align="center">1 (0.7)</td>
							</tr>
							<tr>
								<td>Beta blocker, ARNi, Diuretic</td>
								<td align="center">1 (0.7)</td>
							</tr>
							<tr>
								<td>Beta-blocker, SGLT2 inhibitor, Diuretic</td>
								<td align="center">1 (0.7)</td>
							</tr>
							<tr>
								<td>ACEi/ARB, Mineralocorticoid antagonist, Diuretic</td>
								<td align="center">1 (0.7)</td>
							</tr>
							<tr>
								<td><bold>4 medications</bold></td>
								<td align="center"><bold>43 (29.2)</bold></td>
							</tr>
							<tr>
								<td>Beta blocker, ACEi/ARB, Mineralocorticoid antagonist, iSGLT2</td>
								<td align="center">12 (8.2)</td>
							</tr>
							<tr>
								<td>Beta blocker, ACEi/ARB, iSGLT2, Diuretic</td>
								<td align="center">10 (6.8)</td>
							</tr>
							<tr>
								<td>Beta blocker, ACEi/ARB, Mineralocorticoid antagonist, Diuretic</td>
								<td align="center">8 (5.4)</td>
							</tr>
							<tr>
								<td>Beta blocker, Mineralocorticoid antagonist, ARNi, iSGLT2</td>
								<td align="center">3 (2.0)</td>
							</tr>
							<tr>
								<td>Beta blocker, Mineralocorticoid antagonist, ARNi, Diuretic</td>
								<td align="center">3 (2.0)</td>
							</tr>
							<tr>
								<td>Beta blocker, Mineralocorticoid antagonist, iSGLT2, Diuretic</td>
								<td align="center">3 (2.0)</td>
							</tr>
							<tr>
								<td>ACEi/ARB, Mineralocorticoid Antagonist, iSGLT2, Diuretic</td>
								<td align="center">2 (1.4)</td>
							</tr>
							<tr>
								<td>Beta blocker, ARNi, iSGLT2, Diuretic</td>
								<td align="center">1 (0.7)</td>
							</tr>
							<tr>
								<td>ACEi/ARB, Mineralocorticoid Antagonist, ARNi, iSGLT2</td>
								<td align="center">1 (0.7)</td>
							</tr>
							<tr>
								<td><bold>5 medications</bold></td>
								<td align="center"><bold>37 (25.2)</bold></td>
							</tr>
							<tr>
								<td>Beta blocker, ACEi/ARB, Mineralocorticoid antagonist, iSGLT2, Diuretic</td>
								<td align="center">27 (18.4)</td>
							</tr>
							<tr>
								<td>Beta blocker, Mineralocorticoid antagonist, ARNi, iSGLT2, Diuretic</td>
								<td align="center">7 (4.8)</td>
							</tr>
							<tr>
								<td>Beta blocker, ACEi/ARB, Mineralocorticoid antagonist, ARNi, iSGLT2</td>
								<td align="center">2 (1.4)</td>
							</tr>
							<tr>
								<td>ACEi/ARB, Mineralocorticoid antagonist, ARNi, iSGLT2, Diuretic</td>
								<td align="center">1 (0.7)</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN2">
							<p>ACEi/ARB: angiotensin-converting enzyme inhibitor / Angiotensin receptor blocker; iSGLT2: sodium/glucose cotransporter type 2 inhibitor; ARNi: neprilysin inhibitor; Diuretic: loop diuretic. Source: Research data, 2024.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
			</p>
		</sec>
		<sec sec-type="discussion">
			<title>Discussion</title>
			<p>HFrEF is a condition that presents negative physiological, economic, and social impacts. In this context, analyzing the clinical and epidemiological profile of patients with this condition is essential to support strategies aimed at reducing its impacts.</p>
			<p>In the present study, the population with HFrEF had a mean age of 68.14 years, with a predominance of males (57.8%). Age is recognized as an important risk factor for HF and cardiovascular diseases in general, since aging is associated with progressive deterioration of cardiac structure and function, increasing susceptibility to the development of the disease.<sup><xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B12">12</xref></sup> It is estimated that approximately 1% of individuals over 50 years of age are affected by HF, and this number doubles with each decade of life, making HF a major cause of mortality in the elderly.<sup><xref ref-type="bibr" rid="B13">13</xref></sup></p>
			<p>Regarding sex, the higher prevalence of men observed in this study is consistent with data from the literature, which attributes this predominance to greater exposure to ischemic risk factors, as well as hormonal differences and pathophysiological mechanisms that favor systolic dysfunction.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> These findings are consistent with previous studies, such as those by Albuquerque et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> (2015), Desai et al.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> (2021), Petersen et al.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> (2021), and Tsao et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> (2023), which also describe predominantly elderly populations with HFrEF and a higher prevalence of males.</p>
			<p>Regarding race/color, this study observed a predominance of white individuals, corresponding to 88.4% of the population with HFrEF. This finding differs from international epidemiological data, in which black individuals present a higher incidence of HF, earlier onset of the disease, and worse clinical outcomes, partly due to the higher prevalence of risk factors such as hypertension, obesity, and systolic dysfunction.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> Epidemiological assessments in different countries demonstrate a substantially higher burden in this population, both in terms of disease occurrence and hospitalizations.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B18">18</xref></sup> However, in the Brazilian context, particularly in the southern region, a higher percentage of heart failure among white individuals may reflect the interaction between regional genetic composition, the epidemiological profile of etiologies, and the social determinants of health. Corroborating this scenario, the study by Albuquerque et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> (2015), conducted in a Brazilian population, identified a predominance of individuals of self-reported white race/color (59%), showing similarity with the findings of the present study.</p>
			<p>Several studies demonstrate that the presence of comorbidities in patients with HFrEF negatively impacts prognosis, contributing to increased mortality, readmissions, and a decline in quality of life.<sup><xref ref-type="bibr" rid="B19">19</xref>-<xref ref-type="bibr" rid="B22">22</xref></sup>Among the comorbidities most frequently associated with HFrEF are systemic arterial hypertension, coronary artery disease, obesity, diabetes mellitus, and acute myocardial infarction.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B23">23</xref></sup> Furthermore, the presence of multiple comorbidities is frequent in this population, and the number of associated conditions is directly related to worse clinical outcomes. In this sense, the identification and active management of these comorbidities are fundamental in the approach to these patients.<sup><xref ref-type="bibr" rid="B20">20</xref>-<xref ref-type="bibr" rid="B22">22</xref></sup></p>
			<p>Ischemic heart disease is recognized as the main cause of HFrEF and was identified in 31.3% of the population in the present study. This proportion is comparable to that described by Dutra et al.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> (2022), who observed a prevalence of 26.3%, but lower than that reported by Petersen et al.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> (2021), who found 46.3% of patients with ischemic heart disease. In large international registries and reviews, this proportion is even higher, with more than 50% of patients with HFrEF presenting ischemic heart disease as an underlying cause.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B24">24</xref></sup> The presence of ischemia is associated with a worse prognosis, a higher risk of arrhythmias and hospitalizations, and influences the response to pharmacological treatment and the indication for devices such as implantable cardioverter-defibrillators.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B25">25</xref></sup></p>
			<p>Systemic arterial hypertension was observed in 68.7% of patients in this study and constitutes one of the main modifiable risk factors for the development of HFrEF. The central pathophysiological mechanism involves chronic overload, with consequent ventricular remodeling, culminating in systolic dysfunction and reduced ejection fraction.<sup><xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B27">27</xref></sup>The high prevalence of hypertension observed in this sample is consistent with epidemiological data, which indicate a frequency between 57% and 75% in patients with HFrEF, in addition to contributing to approximately 20% to 30% of HF cases, with a greater impact in younger populations.<sup><xref ref-type="bibr" rid="B28">28</xref></sup> The risk is dose-dependent, so that higher blood pressure levels proportionally increase the risk of heart failure.<sup><xref ref-type="bibr" rid="B26">26</xref></sup> Furthermore, the presence of hypertension in patients with HFrEF is associated with a worse prognosis, a higher risk of hospitalizations, and mortality. Thus, rigorous blood pressure control is fundamental in both the prevention and management of HF, since reducing blood pressure levels can improve symptoms and cardiac function.<sup><xref ref-type="bibr" rid="B28">28</xref></sup></p>
			<p>In the present study, diabetes mellitus was identified in 56.5% of patients. Its relationship with HFrEF is considered bidirectional and multifactorial. Diabetes constitutes an independent and potent risk factor for the development of HFrEF, increasing this risk by more than two times, even after adjusting for other factors such as hypertension and coronary artery disease. This risk is mediated by both indirect mechanisms and direct effects on the myocardium, culminating in fibrosis and ventricular dysfunction.<sup><xref ref-type="bibr" rid="B29">29</xref>-<xref ref-type="bibr" rid="B31">31</xref></sup> The prevalence of diabetes in patients with HFrEF is high, around 40% in large cohorts, and its presence is associated with a worse prognosis, with a higher risk of hospitalization and mortality.<sup><xref ref-type="bibr" rid="B32">32</xref>,<xref ref-type="bibr" rid="B33">33</xref></sup> The management of patients with HFrEF and diabetes requires an integrated approach, including rigorous glycemic control and the use of agents with proven cardiovascular benefit, such as sodium-glucose cotransporter 2 inhibitors (iSGLT2), which reduce hospitalizations and mortality from heart failure and are recommended by national and international guidelines.<sup><xref ref-type="bibr" rid="B32">32</xref>,<xref ref-type="bibr" rid="B34">34</xref></sup></p>
			<p>Obesity was identified in 25.5% of the patients with HFrEF evaluated, constituting a risk factor not only for systemic arterial hypertension, dyslipidemia, and diabetes mellitus, but also for the development of left ventricular hypertrophy. This is a condition that exerts indirect effects on HF, through the development of risk factors, as well as direct effects on the myocardium.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> The association between obesity and HF is consistently described in the literature, with international studies reporting a prevalence of around 23%.<sup><xref ref-type="bibr" rid="B35">35</xref></sup> Additionally, the cohort study by Lédo et al. (2025)<sup><xref ref-type="bibr" rid="B19">19</xref></sup> stands out, which identified important modifiable risk factors in the Brazilian population, reinforcing the need for preventive strategies and public policies aimed at early detection and management of HF.</p>
			<p>The LVEF observed in this study had a mean of 28.54 ± 6.72%, consistent with various studies described in the literature. The association between reduced LVEF and a worse prognosis in patients with HFrEF is well established, and studies indicate that most patients with HFrEF have a mean LVEF between 25% and 35%.<sup><xref ref-type="bibr" rid="B23">23</xref>,<xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr" rid="B37">37</xref></sup> As LVEF decreases, a progressive increase in the risk of mortality, hospitalizations, and adverse events is observed, regardless of other clinical factors.<sup><xref ref-type="bibr" rid="B38">38</xref>,<xref ref-type="bibr" rid="B39">39</xref></sup> In this context, LVEF remains one of the main parameters for the evaluation and follow-up of patients with HFrEF, being widely validated by international studies and consensus guidelines.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B40">40</xref></sup></p>
			<p>In the present study, only 34.8% of patients with HFrEF were concomitantly using the four recommended classes of prognostic-modifying drugs. Current pharmacological treatment for HFrEF advocates the early initiation of four fundamental classes of medications: renin-angiotensin system inhibitors or angiotensin-neprilysin receptor inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and iSGLT2. This therapeutic strategy is supported by consensus among European, American, and Brazilian guidelines, based on robust evidence of reduced mortality and hospitalizations.<sup><xref ref-type="bibr" rid="B41">41</xref>,<xref ref-type="bibr" rid="B42">42</xref></sup> Loop diuretics constitute another widely used drug class, indicated for symptomatic control of congestion, without prognostic impact.<sup><xref ref-type="bibr" rid="B43">43</xref></sup> Despite well-established recommendations, studies demonstrate that adherence to triple or quadruple therapy remains suboptimal in clinical practice, with less than half of eligible patients receiving all recommended classes.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B44">44</xref></sup>Factors such as the complexity of the therapeutic regimen, polypharmacy, the presence of comorbidities, adverse effects, socioeconomic difficulties, and barriers in the health system contribute to low adherence.<sup><xref ref-type="bibr" rid="B43">43</xref></sup> This low adherence is concerning, as it can favor disease decompensation<sup><xref ref-type="bibr" rid="B16">16</xref></sup> and contribute to high morbidity, mortality, and associated costs.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
			<p>The mortality rate in patients with HFrEF remains high, even with therapeutic advances. Most deaths in this population are due to cardiovascular causes, mainly progressive heart failure and sudden death.<sup><xref ref-type="bibr" rid="B45">45</xref></sup> The present study found that 12.9% of patients with HFrEF died during the study period. In large international registries and multicenter studies, the 1-year mortality rate for outpatients with HFrEF is approximately 8% to 9%. In patients hospitalized for decompensation, this rate can reach 17% to 18%.<sup><xref ref-type="bibr" rid="B46">46</xref></sup> In Brazil, the BREATHE study<sup><xref ref-type="bibr" rid="B1">1</xref></sup> observed mortality from any cause in 12.6% of cases, a result similar to that found in the present study. In turn, Desai et al.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> (2021) reported an even higher percentage of 27.4%. These findings demonstrate that HFrEF continues to represent a significant public health problem, reinforcing the need for rigorous implementation of pharmacological therapy recommended by guidelines to modify the prognosis of these patients.</p>
			<sec>
				<title>Study limitations</title>
				<p>Several limitations inherent to this study should be considered. The study was conducted in a single tertiary care center, a regional referral center, which may limit the external validity of the results. Furthermore, a sample of 147 individuals may not adequately represent the diversity of the population, leading to biased results. This study did not aim to evaluate medication dosages due to the lack of standardization in recording this information in medical records. However, understanding the relevance of this analysis, it is suggested that it be included in future studies for further discussion. Additionally, the data were collected from electronic medical records; therefore, the accuracy and completeness of the information in the records may vary, interfering with the analyses. Furthermore, different professionals may record information in different ways, which can lead to inconsistencies and variability in the collected data.</p>
			</sec>
		</sec>
		<sec sec-type="conclusions">
			<title>Conclusions</title>
			<p>This study described the clinical, epidemiological, and therapeutic profile of patients with HFrEF treated at a reference hospital in southern Brazil, highlighting a predominantly elderly, male population with a high burden of comorbidities, significantly reduced ejection fraction, and relevant in-hospital mortality (Central Illustration).</p>
			<p>The results demonstrate that, despite the consolidated recommendations of national and international guidelines, the optimization of pharmacological therapy is still limited in actual clinical practice. These findings highlight the existence of a gap between clinical guidelines and care practice, reinforcing the need for strategies aimed at optimizing the pharmacological treatment of HFrEF. Understanding the clinical and therapeutic profile of this population can contribute to improving the management of heart failure and reducing adverse outcomes in similar care settings.</p>
		</sec>
	</body>
	<back>
		<ref-list>
			<title>References</title>
			<ref id="B1">
				<label>1</label>
				<mixed-citation>1. Albuquerque DC, Souza JD Neto, Bacal F, Rohde LE, Bernardez-Pereira S, Berwanger O, et al. I Brazilian Registry of Heart Failure - Clinical Aspects, Care Quality and Hospitalization Outcomes. Arq Bras Cardiol. 2015;104(6):433-42. doi: 10.5935/abc.20150031.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Albuquerque</surname>
							<given-names>DC</given-names>
						</name>
						<name>
							<surname>Souza</surname>
							<given-names>JD</given-names>
							<suffix>Neto</suffix>
						</name>
						<name>
							<surname>Bacal</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Rohde</surname>
							<given-names>LE</given-names>
						</name>
						<name>
							<surname>Bernardez-Pereira</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Berwanger</surname>
							<given-names>O</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>I Brazilian Registry of Heart Failure - Clinical Aspects, Care Quality and Hospitalization Outcomes</article-title>
					<source>Arq Bras Cardiol</source>
					<year>2015</year>
					<volume>104</volume>
					<issue>6</issue>
					<fpage>433</fpage>
					<lpage>442</lpage>
					<pub-id pub-id-type="doi">10.5935/abc.20150031</pub-id>
				</element-citation>
			</ref>
			<ref id="B2">
				<label>2</label>
				<mixed-citation>2. Roger VL. Epidemiology of Heart Failure: A Contemporary Perspective. Circ Res. 2021;128(10):1421-34. doi: 10.1161/CIRCRESAHA.121.318172.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Roger</surname>
							<given-names>VL</given-names>
						</name>
					</person-group>
					<article-title>Epidemiology of Heart Failure: A Contemporary Perspective</article-title>
					<source>Circ Res</source>
					<year>2021</year>
					<volume>128</volume>
					<issue>10</issue>
					<fpage>1421</fpage>
					<lpage>1434</lpage>
					<pub-id pub-id-type="doi">10.1161/CIRCRESAHA.121.318172</pub-id>
				</element-citation>
			</ref>
			<ref id="B3">
				<label>3</label>
				<mixed-citation>3. Savarese G, Becher PM, Lund LH, Seferovic P, Rosano GMC, Coats AJS. Global Burden of Heart Failure: A Comprehensive and Updated Review of Epidemiology. Cardiovasc Res. 2023;118(17):3272-87. doi: 10.1093/cvr/cvac013.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Savarese</surname>
							<given-names>G</given-names>
						</name>
						<name>
							<surname>Becher</surname>
							<given-names>PM</given-names>
						</name>
						<name>
							<surname>Lund</surname>
							<given-names>LH</given-names>
						</name>
						<name>
							<surname>Seferovic</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Rosano</surname>
							<given-names>GMC</given-names>
						</name>
						<name>
							<surname>Coats</surname>
							<given-names>AJS</given-names>
						</name>
					</person-group>
					<article-title>Global Burden of Heart Failure: A Comprehensive and Updated Review of Epidemiology</article-title>
					<source>Cardiovasc Res</source>
					<year>2023</year>
					<volume>118</volume>
					<issue>17</issue>
					<fpage>3272</fpage>
					<lpage>3287</lpage>
					<pub-id pub-id-type="doi">10.1093/cvr/cvac013</pub-id>
				</element-citation>
			</ref>
			<ref id="B4">
				<label>4</label>
				<mixed-citation>4. Ziaeian B, Fonarow GC. Epidemiology and Aetiology of Heart Failure. Nat Rev Cardiol. 2016;13(6):368-78. doi: 10.1038/nrcardio.2016.25.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Ziaeian</surname>
							<given-names>B</given-names>
						</name>
						<name>
							<surname>Fonarow</surname>
							<given-names>GC</given-names>
						</name>
					</person-group>
					<article-title>Epidemiology and Aetiology of Heart Failure</article-title>
					<source>Nat Rev Cardiol</source>
					<year>2016</year>
					<volume>13</volume>
					<issue>6</issue>
					<fpage>368</fpage>
					<lpage>378</lpage>
					<pub-id pub-id-type="doi">10.1038/nrcardio.2016.25</pub-id>
				</element-citation>
			</ref>
			<ref id="B5">
				<label>5</label>
				<mixed-citation>5. Bui AL, Horwich TB, Fonarow GC. Epidemiology and Risk Profile of Heart Failure. Nat Rev Cardiol. 2011;8(1):30-41. doi: 10.1038/nrcardio.2010.165.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Bui</surname>
							<given-names>AL</given-names>
						</name>
						<name>
							<surname>Horwich</surname>
							<given-names>TB</given-names>
						</name>
						<name>
							<surname>Fonarow</surname>
							<given-names>GC</given-names>
						</name>
					</person-group>
					<article-title>Epidemiology and Risk Profile of Heart Failure</article-title>
					<source>Nat Rev Cardiol</source>
					<year>2011</year>
					<volume>8</volume>
					<issue>1</issue>
					<fpage>30</fpage>
					<lpage>41</lpage>
					<pub-id pub-id-type="doi">10.1038/nrcardio.2010.165</pub-id>
				</element-citation>
			</ref>
			<ref id="B6">
				<label>6</label>
				<mixed-citation>6. Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, et al. Heart Disease and Stroke Statistics-2023 Update: A Report from the American Heart Association. Circulation. 2023;147(8):e93-e621. doi: 10.1161/CIR.0000000000001123.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Tsao</surname>
							<given-names>CW</given-names>
						</name>
						<name>
							<surname>Aday</surname>
							<given-names>AW</given-names>
						</name>
						<name>
							<surname>Almarzooq</surname>
							<given-names>ZI</given-names>
						</name>
						<name>
							<surname>Anderson</surname>
							<given-names>CAM</given-names>
						</name>
						<name>
							<surname>Arora</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Avery</surname>
							<given-names>CL</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Heart Disease and Stroke Statistics-2023 Update: A Report from the American Heart Association</article-title>
					<source>Circulation</source>
					<year>2023</year>
					<volume>147</volume>
					<issue>8</issue>
					<fpage>e93</fpage>
					<lpage>e621</lpage>
					<pub-id pub-id-type="doi">10.1161/CIR.0000000000001123</pub-id>
				</element-citation>
			</ref>
			<ref id="B7">
				<label>7</label>
				<mixed-citation>7. Ebong IA, Goff DC Jr, Rodriguez CJ, Chen H, Bertoni AG. Mechanisms of Heart Failure in Obesity. Obes Res Clin Pract. 2014;8(6):e540-8. doi: 10.1016/j.orcp.2013.12.005.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Ebong</surname>
							<given-names>IA</given-names>
						</name>
						<name>
							<surname>Goff</surname>
							<given-names>DC</given-names>
							<suffix>Jr</suffix>
						</name>
						<name>
							<surname>Rodriguez</surname>
							<given-names>CJ</given-names>
						</name>
						<name>
							<surname>Chen</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Bertoni</surname>
							<given-names>AG</given-names>
						</name>
					</person-group>
					<article-title>Mechanisms of Heart Failure in Obesity</article-title>
					<source>Obes Res Clin Pract</source>
					<year>2014</year>
					<volume>8</volume>
					<issue>6</issue>
					<fpage>e540</fpage>
					<lpage>e548</lpage>
					<pub-id pub-id-type="doi">10.1016/j.orcp.2013.12.005</pub-id>
				</element-citation>
			</ref>
			<ref id="B8">
				<label>8</label>
				<mixed-citation>8. Triposkiadis F, Giamouzis G, Parissis J, Starling RC, Boudoulas H, Skoularigis J, et al. Reframing the Association and Significance of Co-Morbidities in Heart Failure. Eur J Heart Fail. 2016;18(7):744-58. doi: 10.1002/ejhf.600.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Triposkiadis</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Giamouzis</surname>
							<given-names>G</given-names>
						</name>
						<name>
							<surname>Parissis</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Starling</surname>
							<given-names>RC</given-names>
						</name>
						<name>
							<surname>Boudoulas</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Skoularigis</surname>
							<given-names>J</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Reframing the Association and Significance of Co-Morbidities in Heart Failure</article-title>
					<source>Eur J Heart Fail</source>
					<year>2016</year>
					<volume>18</volume>
					<issue>7</issue>
					<fpage>744</fpage>
					<lpage>758</lpage>
					<pub-id pub-id-type="doi">10.1002/ejhf.600</pub-id>
				</element-citation>
			</ref>
			<ref id="B9">
				<label>9</label>
				<mixed-citation>9. Murphy SP, Ibrahim NE, Januzzi JL Jr. Heart Failure with Reduced Ejection Fraction: A Review. JAMA. 2020;324(5):488-504. doi: 10.1001/jama.2020.10262.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Murphy</surname>
							<given-names>SP</given-names>
						</name>
						<name>
							<surname>Ibrahim</surname>
							<given-names>NE</given-names>
						</name>
						<name>
							<surname>Januzzi</surname>
							<given-names>JL</given-names>
							<suffix>Jr</suffix>
						</name>
					</person-group>
					<article-title>Heart Failure with Reduced Ejection Fraction: A Review</article-title>
					<source>JAMA</source>
					<year>2020</year>
					<volume>324</volume>
					<issue>5</issue>
					<fpage>488</fpage>
					<lpage>504</lpage>
					<pub-id pub-id-type="doi">10.1001/jama.2020.10262</pub-id>
				</element-citation>
			</ref>
			<ref id="B10">
				<label>10</label>
				<mixed-citation>10. Bocchi EA. Heart Failure in South America. Curr Cardiol Rev. 2013;9(2):147-56. doi: 10.2174/1573403x11309020007.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Bocchi</surname>
							<given-names>EA</given-names>
						</name>
					</person-group>
					<article-title>Heart Failure in South America</article-title>
					<source>Curr Cardiol Rev</source>
					<year>2013</year>
					<volume>9</volume>
					<issue>2</issue>
					<fpage>147</fpage>
					<lpage>156</lpage>
					<pub-id pub-id-type="doi">10.2174/1573403x11309020007</pub-id>
				</element-citation>
			</ref>
			<ref id="B11">
				<label>11</label>
				<mixed-citation>11. Li H, Hastings MH, Rhee J, Trager LE, Roh JD, Rosenzweig A. Targeting Age-Related Pathways in Heart Failure. Circ Res. 2020;126(4):533-51. doi: 10.1161/CIRCRESAHA.119.315889.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Li</surname>
							<given-names>H</given-names>
						</name>
						<name>
							<surname>Hastings</surname>
							<given-names>MH</given-names>
						</name>
						<name>
							<surname>Rhee</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Trager</surname>
							<given-names>LE</given-names>
						</name>
						<name>
							<surname>Roh</surname>
							<given-names>JD</given-names>
						</name>
						<name>
							<surname>Rosenzweig</surname>
							<given-names>A</given-names>
						</name>
					</person-group>
					<article-title>Targeting Age-Related Pathways in Heart Failure</article-title>
					<source>Circ Res</source>
					<year>2020</year>
					<volume>126</volume>
					<issue>4</issue>
					<fpage>533</fpage>
					<lpage>551</lpage>
					<pub-id pub-id-type="doi">10.1161/CIRCRESAHA.119.315889</pub-id>
				</element-citation>
			</ref>
			<ref id="B12">
				<label>12</label>
				<mixed-citation>12. Lakatta EG, Levy D. Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part I: Aging Arteries: A &quot;Set Up&quot; for Vascular Disease. Circulation. 2003;107(1):139-46. doi: 10.1161/01.cir.0000048892.83521.58..</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lakatta</surname>
							<given-names>EG</given-names>
						</name>
						<name>
							<surname>Levy</surname>
							<given-names>D</given-names>
						</name>
					</person-group>
					<article-title>Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part I: Aging Arteries: A &quot;Set Up&quot; for Vascular Disease</article-title>
					<source>Circulation</source>
					<year>2003</year>
					<volume>107</volume>
					<issue>1</issue>
					<fpage>139</fpage>
					<lpage>146</lpage>
					<pub-id pub-id-type="doi">10.1161/01.cir.0000048892.83521.58</pub-id>
				</element-citation>
			</ref>
			<ref id="B13">
				<label>13</label>
				<mixed-citation>13. Mosterd A, Hoes AW. Clinical Epidemiology of Heart Failure. Heart. 2007;93(9):1137-46. doi: 10.1136/hrt.2003.025270.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Mosterd</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Hoes</surname>
							<given-names>AW</given-names>
						</name>
					</person-group>
					<article-title>Clinical Epidemiology of Heart Failure</article-title>
					<source>Heart</source>
					<year>2007</year>
					<volume>93</volume>
					<issue>9</issue>
					<fpage>1137</fpage>
					<lpage>1146</lpage>
					<pub-id pub-id-type="doi">10.1136/hrt.2003.025270</pub-id>
				</element-citation>
			</ref>
			<ref id="B14">
				<label>14</label>
				<mixed-citation>14. Lam CSP, Arnott C, Beale AL, Chandramouli C, Hilfiker-Kleiner D, Kaye DM, et al. Sex Differences in Heart Failure. Eur Heart J. 2019;40(47):3859-3868c. doi: 10.1093/eurheartj/ehz835.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lam</surname>
							<given-names>CSP</given-names>
						</name>
						<name>
							<surname>Arnott</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Beale</surname>
							<given-names>AL</given-names>
						</name>
						<name>
							<surname>Chandramouli</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Hilfiker-Kleiner</surname>
							<given-names>D</given-names>
						</name>
						<name>
							<surname>Kaye</surname>
							<given-names>DM</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Sex Differences in Heart Failure</article-title>
					<source>Eur Heart J</source>
					<year>2019</year>
					<volume>40</volume>
					<issue>47</issue>
					<fpage>3859</fpage>
					<lpage>3868c</lpage>
					<pub-id pub-id-type="doi">10.1093/eurheartj/ehz835</pub-id>
				</element-citation>
			</ref>
			<ref id="B15">
				<label>15</label>
				<mixed-citation>15. Desai RJ, Mahesri M, Chin K, Levin R, Lahoz R, Studer R, et al. Epidemiologic Characterization of Heart Failure with Reduced or Preserved Ejection Fraction Populations Identified Using Medicare Claims. Am J Med. 2021;134(4):e241-51. doi: 10.1016/j.amjmed.2020.09.038.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Desai</surname>
							<given-names>RJ</given-names>
						</name>
						<name>
							<surname>Mahesri</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Chin</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>Levin</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Lahoz</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Studer</surname>
							<given-names>R</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Epidemiologic Characterization of Heart Failure with Reduced or Preserved Ejection Fraction Populations Identified Using Medicare Claims</article-title>
					<source>Am J Med</source>
					<year>2021</year>
					<volume>134</volume>
					<issue>4</issue>
					<fpage>e241</fpage>
					<lpage>e251</lpage>
					<pub-id pub-id-type="doi">10.1016/j.amjmed.2020.09.038</pub-id>
				</element-citation>
			</ref>
			<ref id="B16">
				<label>16</label>
				<mixed-citation>16. Petersen LC, Danzmann LC, Bartholomay E, Bodanese LC, Donay BG, Magedanz EH, et al. Survival of Patients with Acute Heart Failure and Mid-Range Ejection Fraction in a Developing Country - A Cohort Study in South Brazil. Arq Bras Cardiol. 2021;116(1):14-23. doi: 10.36660/abc.20190427.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Petersen</surname>
							<given-names>LC</given-names>
						</name>
						<name>
							<surname>Danzmann</surname>
							<given-names>LC</given-names>
						</name>
						<name>
							<surname>Bartholomay</surname>
							<given-names>E</given-names>
						</name>
						<name>
							<surname>Bodanese</surname>
							<given-names>LC</given-names>
						</name>
						<name>
							<surname>Donay</surname>
							<given-names>BG</given-names>
						</name>
						<name>
							<surname>Magedanz</surname>
							<given-names>EH</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Survival of Patients with Acute Heart Failure and Mid-Range Ejection Fraction in a Developing Country - A Cohort Study in South Brazil</article-title>
					<source>Arq Bras Cardiol</source>
					<year>2021</year>
					<volume>116</volume>
					<issue>1</issue>
					<fpage>14</fpage>
					<lpage>23</lpage>
					<pub-id pub-id-type="doi">10.36660/abc.20190427</pub-id>
				</element-citation>
			</ref>
			<ref id="B17">
				<label>17</label>
				<mixed-citation>17. White-Williams C, Rossi LP, Bittner VA, Driscoll A, Durant RW, Granger BB, et al. Addressing Social Determinants of Health in the Care of Patients with Heart Failure: A Scientific Statement from the American Heart Association. Circulation. 2020;141(22):e841-63. doi: 10.1161/CIR.0000000000000767.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>White-Williams</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Rossi</surname>
							<given-names>LP</given-names>
						</name>
						<name>
							<surname>Bittner</surname>
							<given-names>VA</given-names>
						</name>
						<name>
							<surname>Driscoll</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Durant</surname>
							<given-names>RW</given-names>
						</name>
						<name>
							<surname>Granger</surname>
							<given-names>BB</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Addressing Social Determinants of Health in the Care of Patients with Heart Failure: A Scientific Statement from the American Heart Association</article-title>
					<source>Circulation</source>
					<year>2020</year>
					<volume>141</volume>
					<issue>22</issue>
					<fpage>e841</fpage>
					<lpage>e863</lpage>
					<pub-id pub-id-type="doi">10.1161/CIR.0000000000000767</pub-id>
				</element-citation>
			</ref>
			<ref id="B18">
				<label>18</label>
				<mixed-citation>18. Fernandes-Silva MM, Shah AM, Hegde S, Goncalves A, Claggett B, Cheng S, et al. Race-Related Differences in Left Ventricular Structural and Functional Remodeling in Response to Increased Afterload: The ARIC Study. JACC Heart Fail. 2017;5(3):157-65. doi: 10.1016/j.jchf.2016.10.011.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Fernandes-Silva</surname>
							<given-names>MM</given-names>
						</name>
						<name>
							<surname>Shah</surname>
							<given-names>AM</given-names>
						</name>
						<name>
							<surname>Hegde</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Goncalves</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Claggett</surname>
							<given-names>B</given-names>
						</name>
						<name>
							<surname>Cheng</surname>
							<given-names>S</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Race-Related Differences in Left Ventricular Structural and Functional Remodeling in Response to Increased Afterload: The ARIC Study</article-title>
					<source>JACC Heart Fail</source>
					<year>2017</year>
					<volume>5</volume>
					<issue>3</issue>
					<fpage>157</fpage>
					<lpage>165</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jchf.2016.10.011</pub-id>
				</element-citation>
			</ref>
			<ref id="B19">
				<label>19</label>
				<mixed-citation>19. Lédo APO, Matos SMA, Almeida MDCC, Aras R. Incidence and Risk Factors for Heart Failure in the ELSA-Brasil Cohort. PLoS One. 2025;20(8):e0329113. doi: 10.1371/journal.pone.0329113.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lédo</surname>
							<given-names>APO</given-names>
						</name>
						<name>
							<surname>Matos</surname>
							<given-names>SMA</given-names>
						</name>
						<name>
							<surname>Almeida</surname>
							<given-names>MDCC</given-names>
						</name>
						<name>
							<surname>Aras</surname>
							<given-names>R</given-names>
						</name>
					</person-group>
					<article-title>Incidence and Risk Factors for Heart Failure in the ELSA-Brasil Cohort</article-title>
					<source>PLoS One</source>
					<year>2025</year>
					<volume>20</volume>
					<issue>8</issue>
					<elocation-id>e0329113</elocation-id>
					<pub-id pub-id-type="doi">10.1371/journal.pone.0329113</pub-id>
				</element-citation>
			</ref>
			<ref id="B20">
				<label>20</label>
				<mixed-citation>20. Lee KS, Park DI, Lee J, Oh O, Kim N, Nam G. Relationship between Comorbidity and Health Outcomes in Patients with Heart Failure: A Systematic Review and Meta-Analysis. BMC Cardiovasc Disord. 2023;23(1):498. doi: 10.1186/s12872-023-03527-x.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lee</surname>
							<given-names>KS</given-names>
						</name>
						<name>
							<surname>Park</surname>
							<given-names>DI</given-names>
						</name>
						<name>
							<surname>Lee</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Oh</surname>
							<given-names>O</given-names>
						</name>
						<name>
							<surname>Kim</surname>
							<given-names>N</given-names>
						</name>
						<name>
							<surname>Nam</surname>
							<given-names>G</given-names>
						</name>
					</person-group>
					<article-title>Relationship between Comorbidity and Health Outcomes in Patients with Heart Failure: A Systematic Review and Meta-Analysis</article-title>
					<source>BMC Cardiovasc Disord</source>
					<year>2023</year>
					<volume>23</volume>
					<issue>1</issue>
					<size units="pages">498</size>
					<pub-id pub-id-type="doi">10.1186/s12872-023-03527-x</pub-id>
				</element-citation>
			</ref>
			<ref id="B21">
				<label>21</label>
				<mixed-citation>21. Miró Ò, Conde-Martel A, Llorens P, Salamanca-Bautista P, Gil V, González-Franco Á, et al. The Influence of Comorbidities on the Prognosis after an Acute Heart Failure Decompensation and Differences According to Ejection Fraction: Results from the EAHFE and RICA Registries. Eur J Intern Med. 2023;111:97-104. doi: 10.1016/j.ejim.2023.02.026..</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Miró</surname>
							<given-names>Ò</given-names>
						</name>
						<name>
							<surname>Conde-Martel</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Llorens</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Salamanca-Bautista</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Gil</surname>
							<given-names>V</given-names>
						</name>
						<name>
							<surname>González-Franco</surname>
							<given-names>Á</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>The Influence of Comorbidities on the Prognosis after an Acute Heart Failure Decompensation and Differences According to Ejection Fraction: Results from the EAHFE and RICA Registries</article-title>
					<source>Eur J Intern Med</source>
					<year>2023</year>
					<volume>111</volume>
					<fpage>97</fpage>
					<lpage>104</lpage>
					<pub-id pub-id-type="doi">10.1016/j.ejim.2023.02.026</pub-id>
				</element-citation>
			</ref>
			<ref id="B22">
				<label>22</label>
				<mixed-citation>22. Pandey A, Vaduganathan M, Arora S, Qamar A, Mentz RJ, Shah SJ, et al. Temporal Trends in Prevalence and Prognostic Implications of Comorbidities among Patients with Acute Decompensated Heart Failure: The ARIC Study Community Surveillance. Circulation. 2020;142(3):230-43. doi: 10.1161/CIRCULATIONAHA.120.047019.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Pandey</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Vaduganathan</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Arora</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Qamar</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Mentz</surname>
							<given-names>RJ</given-names>
						</name>
						<name>
							<surname>Shah</surname>
							<given-names>SJ</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Temporal Trends in Prevalence and Prognostic Implications of Comorbidities among Patients with Acute Decompensated Heart Failure: The ARIC Study Community Surveillance</article-title>
					<source>Circulation</source>
					<year>2020</year>
					<volume>142</volume>
					<issue>3</issue>
					<fpage>230</fpage>
					<lpage>243</lpage>
					<pub-id pub-id-type="doi">10.1161/CIRCULATIONAHA.120.047019</pub-id>
				</element-citation>
			</ref>
			<ref id="B23">
				<label>23</label>
				<mixed-citation>23. Dutra GP, Gomes BFO, Carmo PRD Jr, Petriz JLF, Nascimento EM, Pereira BB, et al. Mortality from Heart Failure with Mid-Range Ejection Fraction. Arq Bras Cardiol. 2022;118(4):694-700. doi: 10.36660/abc.20210050.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Dutra</surname>
							<given-names>GP</given-names>
						</name>
						<name>
							<surname>Gomes</surname>
							<given-names>BFO</given-names>
						</name>
						<name>
							<surname>Carmo</surname>
							<given-names>PRD</given-names>
							<suffix>Jr</suffix>
						</name>
						<name>
							<surname>Petriz</surname>
							<given-names>JLF</given-names>
						</name>
						<name>
							<surname>Nascimento</surname>
							<given-names>EM</given-names>
						</name>
						<name>
							<surname>Pereira</surname>
							<given-names>BB</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Mortality from Heart Failure with Mid-Range Ejection Fraction</article-title>
					<source>Arq Bras Cardiol</source>
					<year>2022</year>
					<volume>118</volume>
					<issue>4</issue>
					<fpage>694</fpage>
					<lpage>700</lpage>
					<pub-id pub-id-type="doi">10.36660/abc.20210050</pub-id>
				</element-citation>
			</ref>
			<ref id="B24">
				<label>24</label>
				<mixed-citation>24. Pagliaro BR, Cannata F, Stefanini GG, Bolognese L. Myocardial Ischemia and Coronary Disease in Heart Failure. Heart Fail Rev. 2020;25(1):53-65. doi: 10.1007/s10741-019-09831-z.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Pagliaro</surname>
							<given-names>BR</given-names>
						</name>
						<name>
							<surname>Cannata</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>Stefanini</surname>
							<given-names>GG</given-names>
						</name>
						<name>
							<surname>Bolognese</surname>
							<given-names>L</given-names>
						</name>
					</person-group>
					<article-title>Myocardial Ischemia and Coronary Disease in Heart Failure</article-title>
					<source>Heart Fail Rev</source>
					<year>2020</year>
					<volume>25</volume>
					<issue>1</issue>
					<fpage>53</fpage>
					<lpage>65</lpage>
					<pub-id pub-id-type="doi">10.1007/s10741-019-09831-z</pub-id>
				</element-citation>
			</ref>
			<ref id="B25">
				<label>25</label>
				<mixed-citation>25. Elgendy IY, Mahtta D, Pepine CJ. Medical Therapy for Heart Failure Caused by Ischemic Heart Disease. Circ Res. 2019;124(11):1520-35. doi: 10.1161/CIRCRESAHA.118.313568.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Elgendy</surname>
							<given-names>IY</given-names>
						</name>
						<name>
							<surname>Mahtta</surname>
							<given-names>D</given-names>
						</name>
						<name>
							<surname>Pepine</surname>
							<given-names>CJ</given-names>
						</name>
					</person-group>
					<article-title>Medical Therapy for Heart Failure Caused by Ischemic Heart Disease</article-title>
					<source>Circ Res</source>
					<year>2019</year>
					<volume>124</volume>
					<issue>11</issue>
					<fpage>1520</fpage>
					<lpage>1535</lpage>
					<pub-id pub-id-type="doi">10.1161/CIRCRESAHA.118.313568</pub-id>
				</element-citation>
			</ref>
			<ref id="B26">
				<label>26</label>
				<mixed-citation>26. Khan SS, Berwanger O, Fiuzat M, McMurray JJ, Narula J, Prabhakaran D, et al. Prioritising the Primary Prevention of Heart Failure. Lancet. 2025;406(10508):1138-53. doi: 10.1016/S0140-6736(25)01393-5.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Khan</surname>
							<given-names>SS</given-names>
						</name>
						<name>
							<surname>Berwanger</surname>
							<given-names>O</given-names>
						</name>
						<name>
							<surname>Fiuzat</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>McMurray</surname>
							<given-names>JJ</given-names>
						</name>
						<name>
							<surname>Narula</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Prabhakaran</surname>
							<given-names>D</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Prioritising the Primary Prevention of Heart Failure</article-title>
					<source>Lancet</source>
					<year>2025</year>
					<volume>406</volume>
					<issue>10508</issue>
					<fpage>1138</fpage>
					<lpage>1153</lpage>
					<pub-id pub-id-type="doi">10.1016/S0140-6736(25)01393-5</pub-id>
				</element-citation>
			</ref>
			<ref id="B27">
				<label>27</label>
				<mixed-citation>27. Metra M, Teerlink JR. Heart Failure. Lancet. 2017;390(10106):1981-95. doi: 10.1016/S0140-6736(17)31071-1.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Metra</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Teerlink</surname>
							<given-names>JR</given-names>
						</name>
					</person-group>
					<article-title>Heart Failure</article-title>
					<source>Lancet</source>
					<year>2017</year>
					<volume>390</volume>
					<issue>10106</issue>
					<fpage>1981</fpage>
					<lpage>1995</lpage>
					<pub-id pub-id-type="doi">10.1016/S0140-6736(17)31071-1</pub-id>
				</element-citation>
			</ref>
			<ref id="B28">
				<label>28</label>
				<mixed-citation>28. Arundel C, Lam PH, Gill GS, Patel S, Panjrath G, Faselis C, et al. Systolic Blood Pressure and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction. J Am Coll Cardiol. 2019;73(24):3054-63. doi: 10.1016/j.jacc.2019.04.022.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Arundel</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Lam</surname>
							<given-names>PH</given-names>
						</name>
						<name>
							<surname>Gill</surname>
							<given-names>GS</given-names>
						</name>
						<name>
							<surname>Patel</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Panjrath</surname>
							<given-names>G</given-names>
						</name>
						<name>
							<surname>Faselis</surname>
							<given-names>C</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Systolic Blood Pressure and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2019</year>
					<volume>73</volume>
					<issue>24</issue>
					<fpage>3054</fpage>
					<lpage>3063</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jacc.2019.04.022</pub-id>
				</element-citation>
			</ref>
			<ref id="B29">
				<label>29</label>
				<mixed-citation>29. Kenny HC, Abel ED. Heart Failure in Type 2 Diabetes Mellitus. Circ Res. 2019;124(1):121-41. doi: 10.1161/CIRCRESAHA.118.311371.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Kenny</surname>
							<given-names>HC</given-names>
						</name>
						<name>
							<surname>Abel</surname>
							<given-names>ED</given-names>
						</name>
					</person-group>
					<article-title>Heart Failure in Type 2 Diabetes Mellitus</article-title>
					<source>Circ Res</source>
					<year>2019</year>
					<volume>124</volume>
					<issue>1</issue>
					<fpage>121</fpage>
					<lpage>141</lpage>
					<pub-id pub-id-type="doi">10.1161/CIRCRESAHA.118.311371</pub-id>
				</element-citation>
			</ref>
			<ref id="B30">
				<label>30</label>
				<mixed-citation>30. Ho KL, Karwi QG, Connolly D, Pherwani S, Ketema EB, Ussher JR, et al. Metabolic, Structural and Biochemical Changes in Diabetes and the Development of Heart Failure. Diabetologia. 2022;65(3):411-23. doi: 10.1007/s00125-021-05637-7.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Ho</surname>
							<given-names>KL</given-names>
						</name>
						<name>
							<surname>Karwi</surname>
							<given-names>QG</given-names>
						</name>
						<name>
							<surname>Connolly</surname>
							<given-names>D</given-names>
						</name>
						<name>
							<surname>Pherwani</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Ketema</surname>
							<given-names>EB</given-names>
						</name>
						<name>
							<surname>Ussher</surname>
							<given-names>JR</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Metabolic, Structural and Biochemical Changes in Diabetes and the Development of Heart Failure</article-title>
					<source>Diabetologia</source>
					<year>2022</year>
					<volume>65</volume>
					<issue>3</issue>
					<fpage>411</fpage>
					<lpage>423</lpage>
					<pub-id pub-id-type="doi">10.1007/s00125-021-05637-7</pub-id>
				</element-citation>
			</ref>
			<ref id="B31">
				<label>31</label>
				<mixed-citation>31. Packer M. Differential Pathophysiological Mechanisms in Heart Failure with a Reduced or Preserved Ejection Fraction in Diabetes. JACC Heart Fail. 2021;9(8):535-549. doi: 10.1016/j.jchf.2021.05.019.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Packer</surname>
							<given-names>M</given-names>
						</name>
					</person-group>
					<article-title>Differential Pathophysiological Mechanisms in Heart Failure with a Reduced or Preserved Ejection Fraction in Diabetes</article-title>
					<source>JACC Heart Fail</source>
					<year>2021</year>
					<volume>9</volume>
					<issue>8</issue>
					<fpage>535</fpage>
					<lpage>549</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jchf.2021.05.019</pub-id>
				</element-citation>
			</ref>
			<ref id="B32">
				<label>32</label>
				<mixed-citation>32. Pop-Busui R, Januzzi JL, Bruemmer D, Butalia S, Green JB, Horton WB, et al. Heart Failure: An Underappreciated Complication of Diabetes. A Consensus Report of the American Diabetes Association. Diabetes Care. 2022;45(7):1670-90. doi: 10.2337/dci22-0014.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Pop-Busui</surname>
							<given-names>R</given-names>
						</name>
						<name>
							<surname>Januzzi</surname>
							<given-names>JL</given-names>
						</name>
						<name>
							<surname>Bruemmer</surname>
							<given-names>D</given-names>
						</name>
						<name>
							<surname>Butalia</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Green</surname>
							<given-names>JB</given-names>
						</name>
						<name>
							<surname>Horton</surname>
							<given-names>WB</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Heart Failure: An Underappreciated Complication of Diabetes. A Consensus Report of the American Diabetes Association</article-title>
					<source>Diabetes Care</source>
					<year>2022</year>
					<volume>45</volume>
					<issue>7</issue>
					<fpage>1670</fpage>
					<lpage>1690</lpage>
					<pub-id pub-id-type="doi">10.2337/dci22-0014</pub-id>
				</element-citation>
			</ref>
			<ref id="B33">
				<label>33</label>
				<mixed-citation>33. Mentz RJ, Kelly JP, von Lueder TG, Voors AA, Lam CS, Cowie MR, et al. Noncardiac Comorbidities in Heart Failure with Reduced versus Preserved Ejection Fraction. J Am Coll Cardiol. 2014;64(21):2281-93. doi: 10.1016/j.jacc.2014.08.036.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Mentz</surname>
							<given-names>RJ</given-names>
						</name>
						<name>
							<surname>Kelly</surname>
							<given-names>JP</given-names>
						</name>
						<name>
							<surname>von Lueder</surname>
							<given-names>TG</given-names>
						</name>
						<name>
							<surname>Voors</surname>
							<given-names>AA</given-names>
						</name>
						<name>
							<surname>Lam</surname>
							<given-names>CS</given-names>
						</name>
						<name>
							<surname>Cowie</surname>
							<given-names>MR</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Noncardiac Comorbidities in Heart Failure with Reduced versus Preserved Ejection Fraction</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2014</year>
					<volume>64</volume>
					<issue>21</issue>
					<fpage>2281</fpage>
					<lpage>2293</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jacc.2014.08.036</pub-id>
				</element-citation>
			</ref>
			<ref id="B34">
				<label>34</label>
				<mixed-citation>34. Marcondes-Braga FG, Moura LAZ, Issa VS, Vieira JL, Rohde LE, Simões MV, et al. Emerging Topics Update of the Brazilian Heart Failure Guideline - 2021. Arq Bras Cardiol. 2021;116(6):1174-212. doi: 10.36660/abc.20210367.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Marcondes-Braga</surname>
							<given-names>FG</given-names>
						</name>
						<name>
							<surname>Moura</surname>
							<given-names>LAZ</given-names>
						</name>
						<name>
							<surname>Issa</surname>
							<given-names>VS</given-names>
						</name>
						<name>
							<surname>Vieira</surname>
							<given-names>JL</given-names>
						</name>
						<name>
							<surname>Rohde</surname>
							<given-names>LE</given-names>
						</name>
						<name>
							<surname>Simões</surname>
							<given-names>MV</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Emerging Topics Update of the Brazilian Heart Failure Guideline - 2021</article-title>
					<source>Arq Bras Cardiol</source>
					<year>2021</year>
					<volume>116</volume>
					<issue>6</issue>
					<fpage>1174</fpage>
					<lpage>1212</lpage>
					<pub-id pub-id-type="doi">10.36660/abc.20210367</pub-id>
				</element-citation>
			</ref>
			<ref id="B35">
				<label>35</label>
				<mixed-citation>35. Kittleson MM, Benjamin EJ, Blumer V, Harrington J, Januzzi JL, McMurray JJV, et al. 2025 ACC Scientific Statement on the Management of Obesity in Adults with Heart Failure: A Report of the American College of Cardiology. J Am Coll Cardiol. 2025;86(20):1953-75. doi: 10.1016/j.jacc.2025.05.008.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Kittleson</surname>
							<given-names>MM</given-names>
						</name>
						<name>
							<surname>Benjamin</surname>
							<given-names>EJ</given-names>
						</name>
						<name>
							<surname>Blumer</surname>
							<given-names>V</given-names>
						</name>
						<name>
							<surname>Harrington</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Januzzi</surname>
							<given-names>JL</given-names>
						</name>
						<name>
							<surname>McMurray</surname>
							<given-names>JJV</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>2025 ACC Scientific Statement on the Management of Obesity in Adults with Heart Failure: A Report of the American College of Cardiology</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2025</year>
					<volume>86</volume>
					<issue>20</issue>
					<fpage>1953</fpage>
					<lpage>1975</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jacc.2025.05.008</pub-id>
				</element-citation>
			</ref>
			<ref id="B36">
				<label>36</label>
				<mixed-citation>36. DeVore AD, Hellkamp AS, Thomas L, Albert NM, Butler J, Patterson JH, et al. Improvement in Left Ventricular Ejection Fraction in Outpatients with Heart Failure with Reduced Ejection Fraction: Data from CHAMP-HF. Circ Heart Fail. 2020;13(7):e006833. doi: 10.1161/CIRCHEARTFAILURE.119.006833.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>DeVore</surname>
							<given-names>AD</given-names>
						</name>
						<name>
							<surname>Hellkamp</surname>
							<given-names>AS</given-names>
						</name>
						<name>
							<surname>Thomas</surname>
							<given-names>L</given-names>
						</name>
						<name>
							<surname>Albert</surname>
							<given-names>NM</given-names>
						</name>
						<name>
							<surname>Butler</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Patterson</surname>
							<given-names>JH</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Improvement in Left Ventricular Ejection Fraction in Outpatients with Heart Failure with Reduced Ejection Fraction: Data from CHAMP-HF</article-title>
					<source>Circ Heart Fail</source>
					<year>2020</year>
					<volume>13</volume>
					<issue>7</issue>
					<elocation-id>e006833</elocation-id>
					<pub-id pub-id-type="doi">10.1161/CIRCHEARTFAILURE.119.006833</pub-id>
				</element-citation>
			</ref>
			<ref id="B37">
				<label>37</label>
				<mixed-citation>37. Lerman BJ, Popat RA, Assimes TL, Heidenreich PA, Wren SM. Association of Left Ventricular Ejection Fraction and Symptoms with Mortality after Elective Noncardiac Surgery among Patients with Heart Failure. JAMA. 2019;321(6):572-9. doi: 10.1001/jama.2019.0156.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Lerman</surname>
							<given-names>BJ</given-names>
						</name>
						<name>
							<surname>Popat</surname>
							<given-names>RA</given-names>
						</name>
						<name>
							<surname>Assimes</surname>
							<given-names>TL</given-names>
						</name>
						<name>
							<surname>Heidenreich</surname>
							<given-names>PA</given-names>
						</name>
						<name>
							<surname>Wren</surname>
							<given-names>SM</given-names>
						</name>
					</person-group>
					<article-title>Association of Left Ventricular Ejection Fraction and Symptoms with Mortality after Elective Noncardiac Surgery among Patients with Heart Failure</article-title>
					<source>JAMA</source>
					<year>2019</year>
					<volume>321</volume>
					<issue>6</issue>
					<fpage>572</fpage>
					<lpage>579</lpage>
					<pub-id pub-id-type="doi">10.1001/jama.2019.0156</pub-id>
				</element-citation>
			</ref>
			<ref id="B38">
				<label>38</label>
				<mixed-citation>38. Carnicelli AP, Clare RM, Hofmann P, Chiswell K, DeVore AD, Vemulapalli S, et al. Clinical Trajectory of Patients with a Worsening Heart Failure Event and Reduced Ventricular Ejection fraction. Am Heart J. 2022;245:110-6. doi: 10.1016/j.ahj.2021.12.003.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Carnicelli</surname>
							<given-names>AP</given-names>
						</name>
						<name>
							<surname>Clare</surname>
							<given-names>RM</given-names>
						</name>
						<name>
							<surname>Hofmann</surname>
							<given-names>P</given-names>
						</name>
						<name>
							<surname>Chiswell</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>DeVore</surname>
							<given-names>AD</given-names>
						</name>
						<name>
							<surname>Vemulapalli</surname>
							<given-names>S</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Clinical Trajectory of Patients with a Worsening Heart Failure Event and Reduced Ventricular Ejection fraction</article-title>
					<source>Am Heart J</source>
					<year>2022</year>
					<volume>245</volume>
					<fpage>110</fpage>
					<lpage>116</lpage>
					<pub-id pub-id-type="doi">10.1016/j.ahj.2021.12.003</pub-id>
				</element-citation>
			</ref>
			<ref id="B39">
				<label>39</label>
				<mixed-citation>39. Liang M, Bian B, Yang Q. Characteristics and Long-Term Prognosis of Patients with Reduced, Mid-Range, and Preserved Ejection Fraction: A Systemic Review and Meta-Analysis. Clin Cardiol. 2022;45(1):5-17. doi: 10.1002/clc.23754.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Liang</surname>
							<given-names>M</given-names>
						</name>
						<name>
							<surname>Bian</surname>
							<given-names>B</given-names>
						</name>
						<name>
							<surname>Yang</surname>
							<given-names>Q</given-names>
						</name>
					</person-group>
					<article-title>Characteristics and Long-Term Prognosis of Patients with Reduced, Mid-Range, and Preserved Ejection Fraction: A Systemic Review and Meta-Analysis</article-title>
					<source>Clin Cardiol</source>
					<year>2022</year>
					<volume>45</volume>
					<issue>1</issue>
					<fpage>5</fpage>
					<lpage>17</lpage>
					<pub-id pub-id-type="doi">10.1002/clc.23754</pub-id>
				</element-citation>
			</ref>
			<ref id="B40">
				<label>40</label>
				<mixed-citation>40. Rosano GMC, Teerlink JR, Kinugawa K, Bayes-Genis A, Chioncel O, Fang J, et al. The Use of Left Ventricular Ejection Fraction in the Diagnosis and Management of Heart Failure. A Clinical Consensus Statement of the Heart Failure Association (HFA) of the ESC, the Heart Failure Society of America (HFSA), and the Japanese Heart Failure Society (JHFS). Eur J Heart Fail. 2025;27(7):1174-87. doi: 10.1002/ejhf.3646.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Rosano</surname>
							<given-names>GMC</given-names>
						</name>
						<name>
							<surname>Teerlink</surname>
							<given-names>JR</given-names>
						</name>
						<name>
							<surname>Kinugawa</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>Bayes-Genis</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Chioncel</surname>
							<given-names>O</given-names>
						</name>
						<name>
							<surname>Fang</surname>
							<given-names>J</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>The Use of Left Ventricular Ejection Fraction in the Diagnosis and Management of Heart Failure. A Clinical Consensus Statement of the Heart Failure Association (HFA) of the ESC, the Heart Failure Society of America (HFSA), and the Japanese Heart Failure Society (JHFS)</article-title>
					<source>Eur J Heart Fail</source>
					<year>2025</year>
					<volume>27</volume>
					<issue>7</issue>
					<fpage>1174</fpage>
					<lpage>1187</lpage>
					<pub-id pub-id-type="doi">10.1002/ejhf.3646</pub-id>
				</element-citation>
			</ref>
			<ref id="B41">
				<label>41</label>
				<mixed-citation>41. van Essen BJ, Ceelen DCH, Ouwerkerk W, Teng TK, Tharshana GN, Hew FM, et al. Pharmacologic Treatment of Heart Failure with Reduced Ejection Fraction: An Updated Systematic Review and Network Meta-Analysis. J Am Coll Cardiol. 2025;86(24):2513-26. doi: 10.1016/j.jacc.2025.08.054.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>van Essen</surname>
							<given-names>BJ</given-names>
						</name>
						<name>
							<surname>Ceelen</surname>
							<given-names>DCH</given-names>
						</name>
						<name>
							<surname>Ouwerkerk</surname>
							<given-names>W</given-names>
						</name>
						<name>
							<surname>Teng</surname>
							<given-names>TK</given-names>
						</name>
						<name>
							<surname>Tharshana</surname>
							<given-names>GN</given-names>
						</name>
						<name>
							<surname>Hew</surname>
							<given-names>FM</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Pharmacologic Treatment of Heart Failure with Reduced Ejection Fraction: An Updated Systematic Review and Network Meta-Analysis</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2025</year>
					<volume>86</volume>
					<issue>24</issue>
					<fpage>2513</fpage>
					<lpage>2526</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jacc.2025.08.054</pub-id>
				</element-citation>
			</ref>
			<ref id="B42">
				<label>42</label>
				<mixed-citation>42. Cannata A, Crespo-Leiro MG, Bromage DI, Ruschitzka F, McDonagh TA. Heart Failure with Reduced Ejection Fraction. Lancet. 2026;407(10527):529-42. doi: 10.1016/S0140-6736(25)01851-3.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Cannata</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Crespo-Leiro</surname>
							<given-names>MG</given-names>
						</name>
						<name>
							<surname>Bromage</surname>
							<given-names>DI</given-names>
						</name>
						<name>
							<surname>Ruschitzka</surname>
							<given-names>F</given-names>
						</name>
						<name>
							<surname>McDonagh</surname>
							<given-names>TA</given-names>
						</name>
					</person-group>
					<article-title>Heart Failure with Reduced Ejection Fraction</article-title>
					<source>Lancet</source>
					<year>2026</year>
					<volume>407</volume>
					<issue>10527</issue>
					<fpage>529</fpage>
					<lpage>542</lpage>
					<pub-id pub-id-type="doi">10.1016/S0140-6736(25)01851-3</pub-id>
				</element-citation>
			</ref>
			<ref id="B43">
				<label>43</label>
				<mixed-citation>43. Maddox TM, Januzzi JL Jr, Allen LA, Breathett K, Brouse S, Butler J, et al. 2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure with Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2024;83(15):1444-88. doi: 10.1016/j.jacc.2023.12.024.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Maddox</surname>
							<given-names>TM</given-names>
						</name>
						<name>
							<surname>Januzzi</surname>
							<given-names>JL</given-names>
							<suffix>Jr</suffix>
						</name>
						<name>
							<surname>Allen</surname>
							<given-names>LA</given-names>
						</name>
						<name>
							<surname>Breathett</surname>
							<given-names>K</given-names>
						</name>
						<name>
							<surname>Brouse</surname>
							<given-names>S</given-names>
						</name>
						<name>
							<surname>Butler</surname>
							<given-names>J</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure with Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2024</year>
					<volume>83</volume>
					<issue>15</issue>
					<fpage>1444</fpage>
					<lpage>1488</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jacc.2023.12.024</pub-id>
				</element-citation>
			</ref>
			<ref id="B44">
				<label>44</label>
				<mixed-citation>44. Greene SJ, Butler J, Albert NM, DeVore AD, Sharma PP, Duffy CI, et al. Medical Therapy for Heart Failure with Reduced Ejection Fraction: The CHAMP-HF Registry. J Am Coll Cardiol. 2018;72(4):351-66. doi: 10.1016/j.jacc.2018.04.070.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Greene</surname>
							<given-names>SJ</given-names>
						</name>
						<name>
							<surname>Butler</surname>
							<given-names>J</given-names>
						</name>
						<name>
							<surname>Albert</surname>
							<given-names>NM</given-names>
						</name>
						<name>
							<surname>DeVore</surname>
							<given-names>AD</given-names>
						</name>
						<name>
							<surname>Sharma</surname>
							<given-names>PP</given-names>
						</name>
						<name>
							<surname>Duffy</surname>
							<given-names>CI</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Medical Therapy for Heart Failure with Reduced Ejection Fraction: The CHAMP-HF Registry</article-title>
					<source>J Am Coll Cardiol</source>
					<year>2018</year>
					<volume>72</volume>
					<issue>4</issue>
					<fpage>351</fpage>
					<lpage>366</lpage>
					<pub-id pub-id-type="doi">10.1016/j.jacc.2018.04.070</pub-id>
				</element-citation>
			</ref>
			<ref id="B45">
				<label>45</label>
				<mixed-citation>45. Settergren C, Benson L, Shahim A, Dahlström U, Thorvaldsen T, Savarese G, et al. Cause-Specific Death in Heart Failure Across the Ejection Fraction Spectrum: A Comprehensive assessment of Over 100 000 Patients in the Swedish Heart Failure Registry. Eur J Heart Fail. 2024;26(5):1150-9. doi: 10.1002/ejhf.3230.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<name>
							<surname>Settergren</surname>
							<given-names>C</given-names>
						</name>
						<name>
							<surname>Benson</surname>
							<given-names>L</given-names>
						</name>
						<name>
							<surname>Shahim</surname>
							<given-names>A</given-names>
						</name>
						<name>
							<surname>Dahlström</surname>
							<given-names>U</given-names>
						</name>
						<name>
							<surname>Thorvaldsen</surname>
							<given-names>T</given-names>
						</name>
						<name>
							<surname>Savarese</surname>
							<given-names>G</given-names>
						</name>
						<etal>et al</etal>
					</person-group>
					<article-title>Cause-Specific Death in Heart Failure Across the Ejection Fraction Spectrum: A Comprehensive assessment of Over 100 000 Patients in the Swedish Heart Failure Registry</article-title>
					<source>Eur J Heart Fail</source>
					<year>2024</year>
					<volume>26</volume>
					<issue>5</issue>
					<fpage>1150</fpage>
					<lpage>1159</lpage>
					<pub-id pub-id-type="doi">10.1002/ejhf.3230</pub-id>
				</element-citation>
			</ref>
			<ref id="B46">
				<label>46</label>
				<mixed-citation>46. Writing Committee Members. HF STATS 2025: Heart Failure Epidemiology and Outcomes Statistics An Updated 2025 Report from the Heart Failure Society of America. J Card Fail. 2026;32(2):439-98. doi: 10.1016/j.cardfail.2025.07.007.</mixed-citation>
				<element-citation publication-type="journal">
					<person-group person-group-type="author">
						<collab>Writing Committee Members</collab>
					</person-group>
					<article-title>HF STATS 2025: Heart Failure Epidemiology and Outcomes Statistics An Updated 2025 Report from the Heart Failure Society of America</article-title>
					<source>J Card Fail</source>
					<year>2026</year>
					<volume>32</volume>
					<issue>2</issue>
					<fpage>439</fpage>
					<lpage>498</lpage>
					<pub-id pub-id-type="doi">10.1016/j.cardfail.2025.07.007</pub-id>
				</element-citation>
			</ref>
		</ref-list>
		<fn-group>
			<fn fn-type="other">
				<label>Study Association:</label>
				<p> This study is not associated with any thesis or dissertation work.</p>
			</fn>
			<fn fn-type="other">
				<label>Ethics Approval and Consent to Participate:</label>
				<p> This study was approved by the Ethics Committee of the Universidade do Extremo Sul Catarinense under the protocol number 6.582.013. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013.</p>
			</fn>
			<fn fn-type="financial-disclosure">
				<label>Sources of Funding:</label>
				<p> There were no external funding sources for this study.</p>
			</fn>
		</fn-group>
	</back>
	<sub-article article-type="translation" id="TRpt" xml:lang="pt">
		<front-stub>
			<article-id pub-id-type="doi">10.36660/abchf.20250027</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Artigo Original</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Análise do Perfil Clínico e Epidemiológico dos Pacientes com Insuficiência Cardíaca com Fração de Ejeção Reduzida em um Hospital do Sul Catarinense</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0007-0473-8706</contrib-id>
					<name>
						<surname>Borges</surname>
						<given-names>Gabriela Aline</given-names>
					</name>
					<role>Concepção e desenho da pesquisa</role>
					<role>Análise e interpretação dos dados e Revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<role>Obtenção de dados</role>
					<role>Análise estatística e Redação do manuscrito</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0005-8241-8447</contrib-id>
					<name>
						<surname>Luca</surname>
						<given-names>Mateus De</given-names>
					</name>
					<role>Concepção e desenho da pesquisa</role>
					<role>Análise e interpretação dos dados e Revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<role>Obtenção de dados</role>
					<role>Análise estatística e Redação do manuscrito</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0009-0001-1840-3938</contrib-id>
					<name>
						<surname>Bolan</surname>
						<given-names>Amanda Cirimbelli</given-names>
					</name>
					<role>Concepção e desenho da pesquisa</role>
					<role>Análise e interpretação dos dados e Revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff1002">
				<label>1</label>
				<country country="BR">Brasil</country>
				<institution content-type="original">Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC – Brasil</institution>
			</aff>
			<author-notes>
				<corresp id="c01002">
					<label>Corespondência:</label> Gabriela Aline Borges. Universidade do Extremo Sul Catarinense (UNESC)- Av. Universitária, 1105. CEP 88806-000, Criciúma, SC - Brasil. E-mail: gabriela.abo@gmail.com </corresp>
				<fn fn-type="coi-statement">
					<label>Potencial Conflito de Interesse:</label>
					<p> Declaro não haver conflito de interesses pertinentes.</p>
				</fn>
				<fn fn-type="edited-by">
					<label>Editor responsável pela revisão:</label>
					<p>Humberto Villacorta</p>
				</fn>
			</author-notes>
			<abstract>
				<title>Resumo</title>
				<sec>
					<title>Fundamento</title>
					<p> A insuficiência cardíaca com fração de ejeção reduzida (ICFEr) representa aproximadamente metade das hospitalizações por insuficiência cardíaca, impacta negativamente a capacidade funcional e a qualidade de vida dos pacientes e está associada a elevados gastos financeiros em saúde.</p>
				</sec>
				<sec>
					<title>Objetivos</title>
					<p> Analisar o perfil clínico e epidemiológico de pacientes com ICFEr em um hospital do sul catarinense no ano de 2023.</p>
				</sec>
				<sec>
					<title>Métodos</title>
					<p> Foram avaliados 147 pacientes com ICFEr em um hospital de referência do sul de Santa Catarina. Os dados foram coletados por meio de prontuários eletrônicos dos quais foram extraídas informações como fração de ejeção do ventrículo esquerdo (FEVE), sexo, idade, raça/cor, peso, altura, medicamentos em uso e condições associadas.</p>
				</sec>
				<sec>
					<title>Resultados</title>
					<p> A média de idade da população em estudo foi de 68,14 ±12,88 anos. O sexo masculino representou 57,8% dos pacientes, e 88,4% eram da raça branca. Do total, 25,5% apresentaram algum grau de obesidade. Hipertensão arterial sistêmica foi observada em 68,7%, diabetes mellitus em 56,5% e cardiomiopatias isquêmicas em 31,3% dos indivíduos. A média do valor da FEVE foi de 28,54 ± 6,72%. A terapia farmacológica tripla preconizada esteve presente em 45,6% dos indivíduos, enquanto a associação com iSGLT2 foi observada em 34,8%.</p>
				</sec>
				<sec>
					<title>Conclusões</title>
					<p> Foi possível identificar o perfil clínico e epidemiológico da população em estudo e, sobretudo, evidenciar que mais da metade dessa população não estava em uso de terapia medicamentosa otimizada. Dessa forma, ressalta-se a importância de dados clínicos e epidemiológicos para revisar e otimizar o manejo dos pacientes.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="pt">
				<title>Palavras-chave:</title>
				<kwd>Insuficiência Cardíaca Sistólica</kwd>
				<kwd>Epidemiologia Clínica</kwd>
				<kwd>Medicina Clínica</kwd>
			</kwd-group>
			<funding-group>
				<funding-statement><bold>Fontes de Financiamento:</bold> O presente estudo não teve fontes de financiamento externas.</funding-statement>
			</funding-group>
		</front-stub>
		<body>
			<sec sec-type="intro">
				<title>Introdução</title>
				<p>A insuficiência cardíaca (IC) tem sido apontada como um importante problema de saúde pública e considerada uma nova epidemia, com elevada mortalidade e morbidade, apesar dos avanços da terapêutica atual.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup> No Brasil, dados do <italic>I Brazilian Registry of Acute Heart Failure</italic> mostram que a IC é uma das principais causas do retorno hospitalar.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Nesse sentido, as tentativas de diminuir o seu fardo social, nas esferas clínica e econômica, se tornaram uma importante prioridade de saúde pública global.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
				<p>Uma ampla gama de condições cardíacas, defeitos hereditários e doenças sistêmicas pode resultar em IC, destacando-se a doença cardíaca isquêmica, doença cardíaca hipertensiva, doença cardíaca congênita, dislipidemia e diabetes.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B4">4</xref></sup> Adicionalmente, idade avançada, sexo masculino,<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup> sedentarismo e tabagismo, são importantes fatores associados à IC, sendo que a contribuição estimada de cada um destes fatores de risco pode variar ao longo do tempo e por raça e etnia.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup></p>
				<p>Para auxiliar na melhor conduta, pacientes com IC podem ser classificados de acordo com alguns aspectos. A diferenciação dos pacientes de acordo com a fração de ejeção do ventrículo esquerdo (FEVE) é de grande importância, uma vez que diferem em relação às principais etiologias, às comorbidades associadas e, principalmente, à resposta à terapêutica.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> A insuficiência cardíaca com fração de ejeção reduzida (ICFEr) é definida como FEVE &lt;40% e impacta negativamente a capacidade funcional e a qualidade de vida dos pacientes, bem como os gastos em saúde. No entanto, apesar dos investimentos na melhoria do manejo da ICFEr, essa condição ainda está associada a altas taxas de hospitalização e mortalidade.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref></sup></p>
				<p>Nesse contexto, a avaliação contínua da epidemiologia da ICFEr é necessária para fornecer uma base científica para a alocação racional dos recursos de saúde e para o desenvolvimento de estratégias destinadas a reduzir os impactos dessa condição.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> Contudo, no Brasil, são escassos os estudos que avaliam, de forma abrangente e prospectiva, as características demográficas, clínicas e prognósticas de pacientes admitidos com diagnóstico clínico de IC.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
				<p>Considerando os impactos funcionais e econômicos da ICFEr e a escassez de estudos sobre essa temática no Brasil, se faz necessária a realização de pesquisas que contribuam para o conhecimento epidemiológico e para a caracterização demográfica e clínica dessa população. Dessa forma, o objetivo do presente estudo foi analisar o perfil clínico e epidemiológico de pacientes com ICFEr em um hospital do sul catarinense.</p>
			</sec>
			<sec sec-type="materials|methods">
				<title>Materiais e métodos</title>
				<sec>
					<title>Aspectos éticos</title>
					<p>O presente estudo foi aprovado pelo Comitê de Ética de Pesquisa e Humanos da instituição de ensino, por meio do parecer n<sup>o</sup> 6.582.013, e pelo Comitê de Ética em Pesquisa do hospital onde o estudo foi realizado, por meio do parecer n<sup>o</sup> 6.705.122.</p>
				</sec>
				<sec>
					<title>Desenho do estudo</title>
					<p>Trata-se de um estudo observacional descritivo, com coleta de dados secundários e abordagem quantitativa.</p>
				</sec>
				<sec>
					<title>População</title>
					<p>Foram analisados 147 pacientes com ICFEr em um hospital do sul catarinense, no período de janeiro a dezembro de 2023. Para seleção inicial desses pacientes, se utilizou a classificação CID-10 correspondente à IC (I50, I50.0, I50.1 e I50.9) registrada nos prontuários. Na sequência, foi considerado o exame de ecocardiograma, utilizando-se os métodos de Teichholz ou Simpson, para classificação da IC de acordo com a FEVE. A <xref ref-type="fig" rid="f01002">Figura 1</xref> ilustra o fluxograma de seleção da amostra do estudo.</p>
					<p>
						<fig id="f01002">
							<label>Figura 1</label>
							<caption>
								<title>– Fluxograma da seleção da amostra do estudo. IC: insuficiência cardíaca; FEVE: fração de ejeção do ventrículo esquerdo; ICFEr: insuficiência cardíaca com fração de ejeção reduzida. Fonte: Elaborado pelos autores.</title>
							</caption>
							<graphic xlink:href="2764-3107-abchf-5-3-e20250027-gf01-pt.tif"/>
						</fig>
					</p>
				</sec>
				<sec>
					<title>Critérios de exclusão</title>
					<p>Não houve exclusões neste estudo.</p>
				</sec>
				<sec>
					<title>Dados coletados</title>
					<p>Os pacientes foram avaliados por meio de prontuários eletrônicos, dos quais foram extraídas as seguintes informações: FEVE (obtida por meio do exame ecocardiográfico), sexo, idade, raça/cor, altura, peso, índice de massa corporal (IMC), medicamentos em uso e comorbidades associadas.</p>
				</sec>
				<sec>
					<title>Análise de dados</title>
					<p>Os dados coletados foram analisados com auxílio do software <italic>IBM Statistical Package for the Social Sciences</italic> (SPSS), versão 23.0. As variáveis idade (anos) e FEVE (%) foram expressas por meio de média e desvio padrão. As variáveis qualitativas (sexo, raça/cor, medicamentos em uso e comorbidades) foram expressas por meio de frequência e porcentagem.</p>
				</sec>
			</sec>
			<sec sec-type="results">
				<title>Resultados</title>
				<p>A Figura Central ilustra os principais achados da pesquisa. Na <xref ref-type="table" rid="t1002">Tabela 1</xref>, se observa o perfil clínico e epidemiológico da população em estudo. A média de idade foi de 68,14 ± 12,88 anos, e o sexo masculino representou 57,8% dos pacientes. Em relação à raça/cor, a branca correspondeu a 88,4%. Quanto ao IMC, 43,4% apresentavam peso adequado, 29,7% tinham sobrepeso e 25,5% apresentavam algum grau de obesidade. Entre as comorbidades, a hipertensão arterial sistêmica esteve presente em 68,7% dos pacientes, o diabetes mellitus em 56,5% e a cardiomiopatia isquêmica em 31,3% da população em estudo. Os betabloqueadores foram os medicamentos em uso por 81,0% dos pacientes, seguidos dos diuréticos (70,1%) e dos iECA/BRA, utilizados por 65,3%. A FEVE teve média de 28,54 ± 6,72%. Dos 147 pacientes analisados, 19 evoluíram a óbito durante a mesma internação.</p>
				<p>
					<table-wrap id="t1002">
						<label>Tabela 1</label>
						<caption>
							<title>– Perfil clínico e epidemiológico de pacientes diagnosticados com insuficiência cardíaca com fração de ejeção reduzida atendidos em um hospital de alta complexidade do sul catarinense no ano de 2023</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th align="left" style="font-weight:normal"> </th>
									<th>Média ± DP, n (%)</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td> </td>
									<td align="center"><bold>n = 147</bold></td>
								</tr>
								<tr>
									<td><bold>Idade (anos)</bold></td>
									<td align="center">68,14 ± 12,88</td>
								</tr>
								<tr>
									<td><bold>Sexo</bold></td>
									<td> </td>
								</tr>
								<tr>
									<td>Masculino</td>
									<td align="center">85 (57,8)</td>
								</tr>
								<tr>
									<td>Feminino</td>
									<td align="center">62 (42,2)</td>
								</tr>
								<tr>
									<td><bold>Raça/Cor</bold></td>
									<td> </td>
								</tr>
								<tr>
									<td>Branca</td>
									<td align="center">130 (88,4)</td>
								</tr>
								<tr>
									<td>Preta</td>
									<td align="center">15 (10,2)</td>
								</tr>
								<tr>
									<td>Parda</td>
									<td align="center">2 (1,4)</td>
								</tr>
								<tr>
									<td><bold>IMC</bold></td>
									<td> </td>
								</tr>
								<tr>
									<td>Abaixo do peso</td>
									<td align="center">2 (1,4)</td>
								</tr>
								<tr>
									<td>Peso adequado</td>
									<td align="center">63 (43,4)</td>
								</tr>
								<tr>
									<td>Sobrepeso</td>
									<td align="center">43 (29,7)</td>
								</tr>
								<tr>
									<td>Obesidade grau I</td>
									<td align="center">27 (18,6)</td>
								</tr>
								<tr>
									<td>Obesidade grau II</td>
									<td align="center">8 (5,5)</td>
								</tr>
								<tr>
									<td>Obesidade grau III</td>
									<td align="center">2 (1,4)</td>
								</tr>
								<tr>
									<td>Sem informação</td>
									<td align="center">2</td>
								</tr>
								<tr>
									<td><bold>Comorbidades</bold></td>
									<td> </td>
								</tr>
								<tr>
									<td>Hipertensão arterial sistêmica</td>
									<td align="center">101 (68,7)</td>
								</tr>
								<tr>
									<td>Diabetes mellitus</td>
									<td align="center">83 (56,5)</td>
								</tr>
								<tr>
									<td>Cardiopatia isquêmica</td>
									<td align="center">46 (31,3)</td>
								</tr>
								<tr>
									<td>Obesidade</td>
									<td align="center">37 (25,2)</td>
								</tr>
								<tr>
									<td>Tabagismo</td>
									<td align="center">32 (21,8)</td>
								</tr>
								<tr>
									<td>Sem comorbidade informada</td>
									<td align="center">6 (4,1)</td>
								</tr>
								<tr>
									<td><bold>Medicamentos em uso</bold></td>
									<td> </td>
								</tr>
								<tr>
									<td>Betabloqueador</td>
									<td align="center">119 (81,0)</td>
								</tr>
								<tr>
									<td>Diurético</td>
									<td align="center">103 (70,1)</td>
								</tr>
								<tr>
									<td>iECA/BRA</td>
									<td align="center">96 (65,3)</td>
								</tr>
								<tr>
									<td>Antagonista mineralocorticoide</td>
									<td align="center">87 (59,2)</td>
								</tr>
								<tr>
									<td>iSGLT2</td>
									<td align="center">83 (56,5)</td>
								</tr>
								<tr>
									<td>INRA</td>
									<td align="center">20 (13,6)</td>
								</tr>
								<tr>
									<td>FEVE (%)</td>
									<td align="center">28,54 ± 6,72</td>
								</tr>
								<tr>
									<td><bold>Óbito</bold></td>
									<td align="center">19 (12,9)</td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN1002">
								<p>IMC: índice de massa corporal; iECA/BRA: inibidor da enzima conversora de angiotensina / Bloqueador do receptor de angiotensina; iSGLT2: inibidor do cotransportador de sódio/glicose tipo 2; INRA: inibidor da neprilisina; Diurético: diurético de alça; FEVE: fração de ejeção do ventrículo esquerdo. Fonte: Dados da pesquisa, 2024.</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
				<p>Na <xref ref-type="table" rid="t2002">Tabela 2</xref>, se observam as medicações em uso pelos pacientes com diagnóstico de ICFEr. Em relação às combinações terapêuticas, 29,2% dos pacientes utilizavam quatro medicamentos, 25,2% utilizavam cinco medicamentos, 22,4% utilizavam três medicamentos e 13,6% faziam uso de duas medicações. Apenas nove pacientes (6,1%) utilizavam uma medicação e cinco (3,4%) não utilizavam nenhum medicamento. Na análise combinatória dos fármacos, considerando o uso de apenas um medicamento, o diurético foi utilizado por 2,7% dos pacientes. A associação do diurético com betabloqueador foi observada em 4,8% dos pacientes, e a combinação desses dois fármacos com iECA/BRA, esteve presente em 6,1%. Entre os pacientes que utilizavam quatro medicamentos, a combinação de betabloqueador, iECA/BRA, antagonista mineralocorticoide e iSGLT2 correspondeu a 8,2%. Foram identificados 27 pacientes (18,4%) em uso da combinação de betabloqueador, iECA/BRA, antagonista mineralocorticoide, iSGLT2 e diurético.</p>
				<p>
					<table-wrap id="t2002">
						<label>Tabela 2</label>
						<caption>
							<title>– Combinação de medicamentos de pacientes diagnosticados com insuficiência cardíaca com fração de ejeção reduzida atendidos em um hospital de alta complexidade do sul catarinense no ano de 2023</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th align="left" style="font-weight:normal"> </th>
									<th>n (%)</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td> </td>
									<td align="center"><bold>n = 147</bold></td>
								</tr>
								<tr>
									<td><bold>Combinação de medicamentos</bold></td>
									<td> </td>
								</tr>
								<tr>
									<td><bold>Nenhum medicamento</bold></td>
									<td align="center"><bold>5 (3,4)</bold></td>
								</tr>
								<tr>
									<td><bold>Apenas 1 medicamento</bold></td>
									<td align="center"><bold>9 (6,1)</bold></td>
								</tr>
								<tr>
									<td>Diurético</td>
									<td align="center">4 (2,7)</td>
								</tr>
								<tr>
									<td>iECA/BRA</td>
									<td align="center">2 (1,4)</td>
								</tr>
								<tr>
									<td>INRA</td>
									<td align="center">2 (1,4)</td>
								</tr>
								<tr>
									<td>Betabloqueador</td>
									<td align="center">1 (0,7)</td>
								</tr>
								<tr>
									<td><bold>2 medicamentos</bold></td>
									<td align="center"><bold>20 (13,6)</bold></td>
								</tr>
								<tr>
									<td>Betabloqueador, Diurético</td>
									<td align="center">7 (4,8)</td>
								</tr>
								<tr>
									<td>iECA/BRA, Diurético</td>
									<td align="center">6 (4,1)</td>
								</tr>
								<tr>
									<td>Betabloqueador, iECA/BRA</td>
									<td align="center">4 (2,7)</td>
								</tr>
								<tr>
									<td>Betabloqueador, iSGLT2</td>
									<td align="center">1 (0,7)</td>
								</tr>
								<tr>
									<td>Antagonista mineralocorticoide, Diurético</td>
									<td align="center">1 (0,7)</td>
								</tr>
								<tr>
									<td>iSGLT2, Diurético</td>
									<td align="center">1 (0,7)</td>
								</tr>
								<tr>
									<td><bold>3 medicamentos</bold></td>
									<td align="center"><bold>33 (22,4)</bold></td>
								</tr>
								<tr>
									<td>Betabloqueador, iECA/BRA, Diurético</td>
									<td align="center">9 (6,1)</td>
								</tr>
								<tr>
									<td>Betabloqueador, Antagonista mineralocorticoide, Diurético</td>
									<td align="center">7 (4,8)</td>
								</tr>
								<tr>
									<td>Betabloqueador, iECA/BRA, iSGLT2</td>
									<td align="center">5 (3,4)</td>
								</tr>
								<tr>
									<td>Betabloqueador, iECA/BRA, Antagonista mineralocorticoide</td>
									<td align="center">4 (2,7)</td>
								</tr>
								<tr>
									<td>Betabloqueador, Antagonista mineralocorticoide, iSGLT2</td>
									<td align="center">2 (1,4)</td>
								</tr>
								<tr>
									<td>Antagonista mineralocorticoide, iSGLT2, Diurético</td>
									<td align="center">2 (1,4)</td>
								</tr>
								<tr>
									<td>Betabloqueador, Antagonista mineralocorticoide, INRA</td>
									<td align="center">1 (0,7)</td>
								</tr>
								<tr>
									<td>Betabloqueador, INRA, Diurético</td>
									<td align="center">1 (0,7)</td>
								</tr>
								<tr>
									<td>Betabloqueador, iSGLT2, Diurético</td>
									<td align="center">1 (0,7)</td>
								</tr>
								<tr>
									<td>iECA/BRA, Antagonista mineralocorticoide, Diurético</td>
									<td align="center">1 (0,7)</td>
								</tr>
								<tr>
									<td><bold>4 medicamentos</bold></td>
									<td align="center"><bold>43 (29,2)</bold></td>
								</tr>
								<tr>
									<td>Betabloqueador, iECA/BRA, Antagonista mineralocorticoide, iSGLT2</td>
									<td align="center">12 (8,2)</td>
								</tr>
								<tr>
									<td>Betabloqueador, iECA/BRA, iSGLT2, Diurético</td>
									<td align="center">10 (6,8)</td>
								</tr>
								<tr>
									<td>Betabloqueador, iECA/BRA, Antagonista mineralocorticoide, Diurético</td>
									<td align="center">8 (5,4)</td>
								</tr>
								<tr>
									<td>Betabloqueador, Antagonista mineralocorticoide, INRA, iSGLT2</td>
									<td align="center">3 (2,0)</td>
								</tr>
								<tr>
									<td>Betabloqueador, Antagonista mineralocorticoide, INRA, Diurético</td>
									<td align="center">3 (2,0)</td>
								</tr>
								<tr>
									<td>Betabloqueador, Antagonista mineralocorticoide, iSGLT2, Diurético</td>
									<td align="center">3 (2,0)</td>
								</tr>
								<tr>
									<td>iECA/BRA, Antagonista mineralocorticoide, iSGLT2, Diurético</td>
									<td align="center">2 (1,4)</td>
								</tr>
								<tr>
									<td>Betabloqueador, INRA, iSGLT2, Diurético</td>
									<td align="center">1 (0,7)</td>
								</tr>
								<tr>
									<td>iECA/BRA, Antagonista mineralocorticoide, INRA, iSGLT2</td>
									<td align="center">1 (0,7)</td>
								</tr>
								<tr>
									<td><bold>5 medicamentos</bold></td>
									<td align="center"><bold>37 (25,2)</bold></td>
								</tr>
								<tr>
									<td>Betabloqueador, iECA/BRA, Antagonista mineralocorticoide, iSGLT2, Diurético</td>
									<td align="center">27 (18,4)</td>
								</tr>
								<tr>
									<td>Betabloqueador, Antagonista mineralocorticoide, INRA, iSGLT2, Diurético</td>
									<td align="center">7 (4,8)</td>
								</tr>
								<tr>
									<td>Betabloqueador, iECA/BRA, Antagonista mineralocorticoide, INRA, iSGLT2</td>
									<td align="center">2 (1,4)</td>
								</tr>
								<tr>
									<td>iECA/BRA, Antagonista mineralocorticoide, INRA, iSGLT2, Diurético</td>
									<td align="center">1 (0,7)</td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN2002">
								<p>iECA/BRA: inibidor da enzima conversora de angiotensina / Bloqueador do receptor de angiotensina; iSGLT2: Inibidor do cotransportador de sódio/glicose tipo 2; INRA: inibidor da neprilisina; Diurético: diurético de alça. Fonte: Dados da pesquisa, 2024.</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
			</sec>
			<sec sec-type="discussion">
				<title>Discussão</title>
				<p>A ICFEr é uma condição que apresenta impactos negativos tanto fisiológicos quanto econômicos e sociais. Nesse contexto, a análise do perfil clínico e epidemiológico de pacientes com essa condição é essencial para embasar estratégias voltadas à redução de seus impactos.</p>
				<p>No presente estudo, a população com ICFEr apresentou média de idade de 68,14 anos, com predomínio do sexo masculino (57,8%). A idade é reconhecida como um importante fator de risco para IC e para as doenças cardiovasculares em geral, uma vez que o envelhecimento está associado à deterioração progressiva da estrutura e da função cardíaca, aumentando a suscetibilidade ao desenvolvimento da doença.<sup><xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B12">12</xref></sup> Estima-se que aproximadamente 1% dos indivíduos com mais de 50 anos sejam acometidos por IC, e esse número dobra a cada década de vida, tornando a IC uma importante causa de mortalidade em idosos.<sup><xref ref-type="bibr" rid="B13">13</xref></sup></p>
				<p>Com relação ao sexo, a maior prevalência de homens observada neste estudo está de acordo com dados da literatura, que atribuem essa predominância à maior exposição a fatores de risco isquêmicos, além de diferenças hormonais e mecanismos fisiopatológicos que favorecem a disfunção sistólica.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> Esses achados são consistentes com estudos prévios, como os de Albuquerque et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> (2015), Desai et al.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> (2021), Petersen et al.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> (2021) e Tsao et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> (2023), que também descrevem populações com ICFEr predominantemente idosas e com maior prevalência do sexo masculino.</p>
				<p>No que concerne à raça/cor, se observou, neste estudo, a predominância de indivíduos de raça/cor branca, correspondendo a 88,4% da população com ICFEr. Esse achado difere de dados epidemiológicos internacionais, nos quais indivíduos negros apresentam maior incidência de IC, início mais precoce da doença e piores desfechos clínicos, em parte devido à maior prevalência de fatores de risco, como hipertensão arterial, obesidade e disfunção sistólica.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> Avaliações epidemiológicas em diferentes países demonstram carga substancialmente maior nessa população, tanto no acometimento quanto nas hospitalizações.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B18">18</xref></sup> Entretanto, no contexto brasileiro, particularmente na região sul, um maior percentual de insuficiência cardíaca entre indivíduos brancos pode ser reflexo da interação entre a composição genética regional, o perfil epidemiológico das etiologias e os determinantes sociais de saúde. Corroborando com esse cenário, o estudo de Albuquerque et al.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> (2015), realizado em população brasileira, identificou predominância de indivíduos de raça/cor branca autorreferida (59%), evidenciando semelhança com os achados do presente estudo.</p>
				<p>Diversos estudos demonstram que a presença de comorbidades em pacientes com ICFEr impacta negativamente o prognóstico, contribuindo para o aumento da mortalidade, das reinternações e para a piora na qualidade de vida.<sup><xref ref-type="bibr" rid="B19">19</xref>-<xref ref-type="bibr" rid="B22">22</xref></sup> Entre as comorbidades mais frequentemente associadas à ICFEr, se destacam hipertensão arterial sistêmica, doença arterial coronariana, obesidade, diabetes mellitus e infarto agudo do miocárdio.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B23">23</xref></sup> Ademais, a presença de múltiplas comorbidades é frequente nessa população, e o número de condições associadas está diretamente relacionado a piores desfechos clínicos. Nesse sentido, a identificação e o manejo ativo dessas comorbidades são fundamentais na abordagem desses pacientes.<sup><xref ref-type="bibr" rid="B20">20</xref>-<xref ref-type="bibr" rid="B22">22</xref></sup></p>
				<p>A doença cardíaca isquêmica é reconhecida como a principal causa de ICFEr e foi identificada em 31,3% da população no presente estudo. Essa proporção é comparável à descrita por Dutra et al.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> (2022), que observaram prevalência de 26,3%, porém inferior à reportada por Petersen et al.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> (2021), que encontraram 46,3% dos pacientes com doença cardíaca isquêmica. Em grandes registros e revisões internacionais, essa proporção é ainda mais elevada, com mais de 50% dos pacientes com ICFEr apresentando doença cardíaca isquêmica como causa subjacente.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B24">24</xref></sup> A presença de isquemia se associa a pior prognóstico, maior risco de arritmias e hospitalizações, além de influenciar a resposta ao tratamento farmacológico e a indicação de dispositivos, como cardiodesfibriladores implantáveis.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B25">25</xref></sup></p>
				<p>A hipertensão arterial sistêmica foi observada em 68,7% dos pacientes no presente estudo e constitui um dos principais fatores de risco modificáveis para o desenvolvimento de ICFEr. O mecanismo fisiopatológico central envolve a sobrecarga crônica, com consequente remodelamento ventricular, culminando em disfunção sistólica e redução da fração de ejeção.<sup><xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B27">27</xref></sup> A elevada prevalência de hipertensão observada nesta amostra é compatível com dados epidemiológicos, que indicam frequência entre 57% e 75% em pacientes com ICFEr, além de contribuição para aproximadamente 20% a 30% dos casos de IC, com maior impacto em populações mais jovens.<sup><xref ref-type="bibr" rid="B28">28</xref></sup> O risco é dose-dependente, de modo que níveis mais elevados de pressão arterial aumentam proporcionalmente o risco de insuficiência cardíaca.<sup><xref ref-type="bibr" rid="B26">26</xref></sup> Além disso, a presença de hipertensão em pacientes com ICFEr está associada a pior prognóstico, maior risco de hospitalizações e mortalidade. Assim, o controle rigoroso da pressão arterial é fundamental tanto na prevenção quanto no manejo da IC, uma vez que a redução dos níveis pressóricos pode melhorar sintomas e função cardíaca.<sup><xref ref-type="bibr" rid="B28">28</xref></sup></p>
				<p>No presente estudo, o diabetes mellitus foi identificado em 56,5% dos pacientes. Sua relação com ICFEr é considerada bidirecional e multifatorial. O diabetes constitui fator de risco independente e potente para o desenvolvimento de ICFEr, aumentando esse risco em mais de duas vezes, mesmo após ajuste para outros fatores como hipertensão arterial e doença arterial coronariana. Tal risco é mediado tanto por mecanismos indiretos, quanto por efeitos diretos sobre o miocárdio, culminando em fibrose e disfunção ventricular.<sup><xref ref-type="bibr" rid="B29">29</xref>-<xref ref-type="bibr" rid="B31">31</xref></sup> A prevalência de diabetes em pacientes com ICFEr é elevada, situando-se em torno de 40% em grandes coortes, e sua presença está associada a pior prognóstico, com maior risco de hospitalização e mortalidade.<sup><xref ref-type="bibr" rid="B32">32</xref>,<xref ref-type="bibr" rid="B33">33</xref></sup> O manejo do paciente com ICFEr e diabetes exige abordagem integrada, incluindo controle glicêmico rigoroso e uso de agentes com benefício cardiovascular comprovado, como os inibidores do cotransportador de sódio-glicose tipo 2 (iSGLT2), os quais reduzem hospitalizações e mortalidade por insuficiência cardíaca, sendo recomendados por diretrizes nacionais e internacionais.<sup><xref ref-type="bibr" rid="B32">32</xref>,<xref ref-type="bibr" rid="B34">34</xref></sup></p>
				<p>A obesidade foi identificada em 25,5% dos pacientes com ICFEr avaliados, configurando-se como fator de risco não apenas para hipertensão arterial sistêmica, dislipidemia e diabetes mellitus, mas também para o desenvolvimento de hipertrofia ventricular esquerda. Trata-se de uma condição que exerce efeitos indiretos sobre a IC, por meio do desenvolvimento de fatores de risco, bem como efeitos diretos sobre o miocárdio.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> A associação entre obesidade e IC é consistentemente descrita na literatura, com estudos internacionais relatando prevalência em torno de 23%.<sup><xref ref-type="bibr" rid="B35">35</xref></sup> Adicionalmente, se destaca o estudo de coorte de Lédo et al. (2025),<sup><xref ref-type="bibr" rid="B19">19</xref></sup> que identificou importantes fatores de risco modificáveis na população brasileira, reforçando a necessidade de estratégias preventivas e de políticas públicas voltadas para a detecção precoce e ao manejo da IC.</p>
				<p>A FEVE observada neste estudo apresentou média de 28,54 ± 6,72%, sendo compatível com diferentes estudos descritos na literatura. A associação entre a FEVE reduzida e o pior prognóstico em pacientes com ICFEr é bem estabelecida, e estudos indicam que a maioria dos pacientes com ICFEr apresenta FEVE média entre 25% e 35%.<sup><xref ref-type="bibr" rid="B23">23</xref>,<xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr" rid="B37">37</xref></sup> À medida que a FEVE diminui, se observa aumento progressivo no risco de mortalidade, hospitalizações e eventos adversos, independentemente de outros fatores clínicos.<sup><xref ref-type="bibr" rid="B38">38</xref>,<xref ref-type="bibr" rid="B39">39</xref></sup> Nesse contexto, a FEVE permanece como um dos principais parâmetros para avaliação e seguimento de pacientes com ICFEr, sendo amplamente validada por estudos e consensos internacionais.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B40">40</xref></sup></p>
				<p>No presente estudo, apenas 34,8% dos pacientes com ICFEr encontravam-se em uso concomitante das quatro classes de fármacos modificadores de prognóstico recomendadas. O tratamento farmacológico atual para ICFEr preconiza o início precoce de quatro classes de medicamentos fundamentais: inibidores do sistema renina-angiotensina ou inibidores do receptor de angiotensina-neprilisina, betabloqueadores, antagonistas do receptor de mineralocorticoides e iSGLT2. Essa estratégia terapêutica é respaldada por consenso entre as diretrizes europeia, americana e brasileira, com base em evidências robustas de redução de mortalidade e hospitalizações.<sup><xref ref-type="bibr" rid="B41">41</xref>,<xref ref-type="bibr" rid="B42">42</xref></sup> Os diuréticos de alça constituem outra classe medicamentosa amplamente utilizada, sendo indicados para o controle sintomático da congestão, sem impacto prognóstico.<sup><xref ref-type="bibr" rid="B43">43</xref></sup> Apesar das recomendações bem estabelecidas, estudos demonstram que a adesão à terapia tripla ou quádrupla permanece subótima na prática clínica, com menos da metade dos pacientes elegíveis recebendo todas as classes recomendadas.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B44">44</xref></sup> Fatores como a complexidade do regime terapêutico, a polifarmácia, a presença de comorbidades, os efeitos adversos, as dificuldades socioeconômicas e as barreiras do sistema de saúde contribuem para a baixa adesão.<sup><xref ref-type="bibr" rid="B43">43</xref></sup> Essa baixa adesão é preocupante, uma vez que pode favorecer a descompensação da doença<sup><xref ref-type="bibr" rid="B16">16</xref></sup> e contribuir para a elevada morbidade, mortalidade e custos associados.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
				<p>A taxa de mortalidade em pacientes com ICFEr permanece elevada, mesmo diante dos avanços terapêuticos. A maioria dos óbitos nessa população é de causa cardiovascular, principalmente por IC progressiva e morte súbita.<sup><xref ref-type="bibr" rid="B45">45</xref></sup> O presente estudo constatou que 12,9% dos pacientes com ICFEr evoluíram ao óbito no período estudado. Em grandes registros internacionais e estudos multicêntricos, a mortalidade em 1 ano para pacientes ambulatoriais com ICFEr é de aproximadamente 8% a 9%. Em pacientes hospitalizados por descompensação, esse índice pode alcançar 17% a 18%.<sup><xref ref-type="bibr" rid="B46">46</xref></sup> No Brasil, o estudo BREATHE<sup><xref ref-type="bibr" rid="B1">1</xref></sup> observou mortalidade por qualquer causa em 12,6% dos casos, resultado semelhante ao encontrado no presente estudo. Por sua vez, Desai et al.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> (2021) relataram percentual ainda mais elevado, de 27,4%. Esses achados evidenciam que a ICFEr continua a representar um importante problema de saúde pública, reforçando a necessidade de implementação rigorosa da terapia farmacológica recomendada pelas diretrizes, com o objetivo de modificar o prognóstico desses pacientes.</p>
				<sec>
					<title>Limitações do estudo</title>
					<p>Algumas limitações inerentes ao presente estudo devem ser consideradas. O estudo foi realizado em um único centro de atenção terciária, referência na região, o que pode limitar a validade externa dos resultados. Além disso, uma amostra de 147 indivíduos pode não representar adequadamente a diversidade da população, levando a resultados enviesados. O presente estudo não teve como objetivo avaliar as doses utilizadas das medicações, devido à falta de padronização do registro dessa informação no prontuário. No entanto, entendendo a relevância dessa análise, se sugere que, em estudos futuros, a mesma seja incluída para maiores discussões. Ademais, os dados foram coletados de prontuários eletrônicos; sendo assim, a precisão e a completude das informações nos prontuários podem variar, interferindo nas análises. Somado a isso, diferentes profissionais podem registrar informações de maneiras distintas, o que pode levar a inconsistências e variabilidades nos dados coletados.</p>
				</sec>
			</sec>
			<sec sec-type="conclusions">
				<title>Conclusões</title>
				<p>O presente estudo descreveu o perfil clínico, epidemiológico e terapêutico de pacientes com ICFEr atendidos em um hospital de referência do sul do Brasil, evidenciando uma população predominantemente idosa, do sexo masculino, com elevada carga de comorbidades, fração de ejeção significativamente reduzida e mortalidade intra-hospitalar relevante (Figura Central).</p>
				<p>Os resultados demonstram que, apesar das recomendações consolidadas das diretrizes nacionais e internacionais, a otimização da terapia farmacológica ainda é limitada na prática clínica real. Esses achados ressaltam a existência de uma lacuna entre as diretrizes clínicas e a prática assistencial, reforçando a necessidade de estratégias voltadas à otimização do tratamento farmacológico da ICFEr. A compreensão do perfil clínico e terapêutico dessa população pode contribuir para o aprimoramento do manejo da insuficiência cardíaca e para a redução de desfechos adversos em contextos assistenciais semelhantes.</p>
			</sec>
		</body>
		<back>
			<fn-group>
				<fn fn-type="other">
					<label>Vinculação Acadêmica:</label>
					<p> Não há vinculação deste estudo a programas de pós-graduação.</p>
				</fn>
				<fn fn-type="other">
					<label>Aprovação Ética e Consentimento Informado:</label>
					<p> Este estudo foi aprovado pelo Comitê de Ética da Universidade do Extremo Sul Catarinense sob o número de protocolo 6.582.013. Todos os procedimentos envolvidos nesse estudo estão de acordo com a Declaração de Helsinki de 1975, atualizada em 2013.</p>
				</fn>
				<fn fn-type="financial-disclosure">
					<label>Fontes de Financiamento:</label>
					<p> O presente estudo não teve fontes de financiamento externas.</p>
				</fn>
			</fn-group>
		</back>
	</sub-article>
</article>