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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Heart failure &#40;HF&#41; is a clinical syndrome that affects 1-2&#37; of the adult population&#44; with increasing prevalence with age &#40;&#62;10&#37; in those aged 70 years or over&#41;&#46; Although HF prognosis has improved due to new therapies&#44; it is still a frequent cause for hospitalizations&#44; with a major impact on health care resources&#46; It can be due to several etiologies&#44; but most commonly it derives from myocardial dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Heart failure impacts patients&#8217; quality of life&#44; has an adverse prognosis and is a major cause of death and hospitalization&#46; Following years of research&#44; new advances in pharmacologic and device therapy have been achieved&#44; optimizing patient care&#46; Currently&#44; one of the focuses of scientific research is on the role of biomarkers in diagnosis&#44; therapy guidance and prognosis of HF&#46; This was recently identified as a gap in evidence in the new European Society of Cardiology Heart Failure guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> The search of a biomarker that could help identify patients at high-risk of adverse events and to alter patient management is one of the most sought after objectives in cardiology&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Segura-Salda&#241;a et al<span class="elsevierStyleItalic">&#46;</span><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> aimed to observe the prognostic role of three biomarkers&#44; red blood cell distribution width &#40;RDW&#41;&#44; high-sensitive C-reactive protein &#40;hs-CRP&#41; and interleukin-6 &#40;IL-6&#41; in patients hospitalized for acute HF&#46; In their prospective study with a cohort of 167 non-ischemic HF patients&#44; the authors concluded that IL-6 was an independent predictor of mortality when only considering age&#44; gender and comorbidity confounders&#59; however&#44; its effect was not independent from most important clinical variables&#46; Of the three biomarkers&#44; IL-6 presented the best accuracy for mortality and RDW for severity&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The best cut-off value to predict mortality for IL-6 was 52&#46;9 pg&#47;mL &#40;sensitivity 100&#37;&#59; specificity 75&#46;35&#37;&#59; area under the curve &#40;AUC&#41; 0&#46;91&#41;&#46; As for severity&#44; the best cut-off of RDW was 15&#46;6&#37; &#40;sensitivity 93&#46;6&#37;&#59; specificity 73&#46;33&#37;&#59; AUC 0&#46;87&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In recent years&#44; several studies have addressed the impact of markers related to pro-inflammatory states&#44; in an attempt to determine the prognosis of cardiovascular diseases&#46; In HF&#44; there are increased levels of circulating inflammatory cytokines and some studies suggest that they can predict clinical outcomes&#59; hence&#44; the interest in dosing and establishing a relationship between elevated inflammatory biomarkers and prognosis&#46; Nonetheless&#44; one should not forget that the concentration of these biomarkers increases with aging and in several chronic diseases &#40;both characteristics present in several HF patients&#41;&#46; Of note&#44; the elevated concentration of inflammatory biomarkers can also be a consequence of HF &#40;as a pro-inflammatory illness&#41;&#44; and not the cause&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">High-sensitive CRP is one of the most widely studied biomarkers in several cardiovascular conditions&#46; It is considered a marker of low-grade inflammation&#44; even when there is only lminor CRP elevation&#46; Its role in the assessment of cardiovascular risk is in continuous evolution&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> In this study&#44; hs-CRP was not an independent predictor of mortality&#44; but it was associated with severity &#40;after controlling for age&#44; gender and comorbidities&#41;&#46; However&#44; the sensitivity of hs-CRP was considerably low&#44; thus could limit its role in this clinical context&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Interleukin-6 is a pleiotropic cytokine that rises in response to injury&#46; It activates immune cells and signal protective response&#44; acting as an inflammatory mediator&#46; Its elevation in HF has been previously recognized and is associated with a poorer clinical outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> In this study&#44; IL-6 presented the best accuracy for mortality and its effect on severity was independent from comorbidities&#44; age and gender&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Red blood cell distribution width is a routinely assessed blood count component and is inexpensive and non-invasive&#46; It is a measurement of the heterogeneity of the circulating red blood cells size&#46; RDW was previously associated with ventricular dysfunction<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> and other studies support its better prognosis capacity than natriuretic peptides&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">6&#44;7</span></a> Although it is not completely clear&#44; RDW may be linked to inflammation and ineffective erythropoiesis &#40;for example in renal disease or iron deficiency&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> In this study&#44; RDW was shown to be highly correlated with disease severity&#44; independent of age&#44; gender and comorbidities but not with mortality&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">These biomarkers are not expensive and are available in most hospitals&#44; however they are not routinely used&#44; with the exception of RDW&#46; The information obtained from this article is important&#44; as it adds more data on the use of biomarkers in HF prognosis&#46; More studies with a larger number of patients &#40;and different HF etiologies&#41; are necessary to demonstrate its validity&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">This study is limited as it is a single center study&#44; with a small sample size &#40;n&#61;167&#41; and short follow-up &#40;only in-hospital mortality was assessed&#41;&#46; Of note&#44; it only included 41&#46;3&#37; of patients with HF with reduced ejection fraction&#44; and all patients had non-ischemic HF&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">There are also many other parameters &#40;biomarkers and others&#41; that have been shown to predict morbidity and mortality in HF&#46; However&#44; more than an economic or availability problem&#44; the real limitation of these parameters is their lack of impact on management decisions&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As the authors duly noted&#44; no biomarker is independent from the most important clinical variables&#44; therefore they should not be used for management modification and their use in HF remains academic&#46; With further research&#44; it is hoped that biomarkers can transition from the bench to the bedside&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The search for an ideal biomarker continues as a long overdue promise&#46; Until then&#44; other established laboratory&#47;echocardiographic data and especially clinical status remain paramount to care&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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Editorial comment
Biomarkers in heart failure: A future or a long overdue promise?
Biomarcadores na insuficiência cardíaca: o futuro ou uma promessa adiada?
Miguel Martins de Carvalhoa,b, Paulo Maia Araújoa,c,
Autor para correspondência
pauloamfa@hotmail.com

Corresponding author.
a Cardiology Department, Centro Hospitalar Universitário de São João, Porto, Portugal
b Cardiovascular R&D Center, Faculty of Medicine, University of Porto, Porto, Portugal
c CINTESIS, Centre for Health Technology and Services Research, Faculty of Medicine, University of Porto, Porto, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Heart failure &#40;HF&#41; is a clinical syndrome that affects 1-2&#37; of the adult population&#44; with increasing prevalence with age &#40;&#62;10&#37; in those aged 70 years or over&#41;&#46; Although HF prognosis has improved due to new therapies&#44; it is still a frequent cause for hospitalizations&#44; with a major impact on health care resources&#46; It can be due to several etiologies&#44; but most commonly it derives from myocardial dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Heart failure impacts patients&#8217; quality of life&#44; has an adverse prognosis and is a major cause of death and hospitalization&#46; Following years of research&#44; new advances in pharmacologic and device therapy have been achieved&#44; optimizing patient care&#46; Currently&#44; one of the focuses of scientific research is on the role of biomarkers in diagnosis&#44; therapy guidance and prognosis of HF&#46; This was recently identified as a gap in evidence in the new European Society of Cardiology Heart Failure guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> The search of a biomarker that could help identify patients at high-risk of adverse events and to alter patient management is one of the most sought after objectives in cardiology&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Segura-Salda&#241;a et al<span class="elsevierStyleItalic">&#46;</span><a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> aimed to observe the prognostic role of three biomarkers&#44; red blood cell distribution width &#40;RDW&#41;&#44; high-sensitive C-reactive protein &#40;hs-CRP&#41; and interleukin-6 &#40;IL-6&#41; in patients hospitalized for acute HF&#46; In their prospective study with a cohort of 167 non-ischemic HF patients&#44; the authors concluded that IL-6 was an independent predictor of mortality when only considering age&#44; gender and comorbidity confounders&#59; however&#44; its effect was not independent from most important clinical variables&#46; Of the three biomarkers&#44; IL-6 presented the best accuracy for mortality and RDW for severity&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The best cut-off value to predict mortality for IL-6 was 52&#46;9 pg&#47;mL &#40;sensitivity 100&#37;&#59; specificity 75&#46;35&#37;&#59; area under the curve &#40;AUC&#41; 0&#46;91&#41;&#46; As for severity&#44; the best cut-off of RDW was 15&#46;6&#37; &#40;sensitivity 93&#46;6&#37;&#59; specificity 73&#46;33&#37;&#59; AUC 0&#46;87&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In recent years&#44; several studies have addressed the impact of markers related to pro-inflammatory states&#44; in an attempt to determine the prognosis of cardiovascular diseases&#46; In HF&#44; there are increased levels of circulating inflammatory cytokines and some studies suggest that they can predict clinical outcomes&#59; hence&#44; the interest in dosing and establishing a relationship between elevated inflammatory biomarkers and prognosis&#46; Nonetheless&#44; one should not forget that the concentration of these biomarkers increases with aging and in several chronic diseases &#40;both characteristics present in several HF patients&#41;&#46; Of note&#44; the elevated concentration of inflammatory biomarkers can also be a consequence of HF &#40;as a pro-inflammatory illness&#41;&#44; and not the cause&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">High-sensitive CRP is one of the most widely studied biomarkers in several cardiovascular conditions&#46; It is considered a marker of low-grade inflammation&#44; even when there is only lminor CRP elevation&#46; Its role in the assessment of cardiovascular risk is in continuous evolution&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> In this study&#44; hs-CRP was not an independent predictor of mortality&#44; but it was associated with severity &#40;after controlling for age&#44; gender and comorbidities&#41;&#46; However&#44; the sensitivity of hs-CRP was considerably low&#44; thus could limit its role in this clinical context&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Interleukin-6 is a pleiotropic cytokine that rises in response to injury&#46; It activates immune cells and signal protective response&#44; acting as an inflammatory mediator&#46; Its elevation in HF has been previously recognized and is associated with a poorer clinical outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> In this study&#44; IL-6 presented the best accuracy for mortality and its effect on severity was independent from comorbidities&#44; age and gender&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Red blood cell distribution width is a routinely assessed blood count component and is inexpensive and non-invasive&#46; It is a measurement of the heterogeneity of the circulating red blood cells size&#46; RDW was previously associated with ventricular dysfunction<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> and other studies support its better prognosis capacity than natriuretic peptides&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">6&#44;7</span></a> Although it is not completely clear&#44; RDW may be linked to inflammation and ineffective erythropoiesis &#40;for example in renal disease or iron deficiency&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> In this study&#44; RDW was shown to be highly correlated with disease severity&#44; independent of age&#44; gender and comorbidities but not with mortality&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">These biomarkers are not expensive and are available in most hospitals&#44; however they are not routinely used&#44; with the exception of RDW&#46; The information obtained from this article is important&#44; as it adds more data on the use of biomarkers in HF prognosis&#46; More studies with a larger number of patients &#40;and different HF etiologies&#41; are necessary to demonstrate its validity&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">This study is limited as it is a single center study&#44; with a small sample size &#40;n&#61;167&#41; and short follow-up &#40;only in-hospital mortality was assessed&#41;&#46; Of note&#44; it only included 41&#46;3&#37; of patients with HF with reduced ejection fraction&#44; and all patients had non-ischemic HF&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">There are also many other parameters &#40;biomarkers and others&#41; that have been shown to predict morbidity and mortality in HF&#46; However&#44; more than an economic or availability problem&#44; the real limitation of these parameters is their lack of impact on management decisions&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As the authors duly noted&#44; no biomarker is independent from the most important clinical variables&#44; therefore they should not be used for management modification and their use in HF remains academic&#46; With further research&#44; it is hoped that biomarkers can transition from the bench to the bedside&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The search for an ideal biomarker continues as a long overdue promise&#46; Until then&#44; other established laboratory&#47;echocardiographic data and especially clinical status remain paramount to care&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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