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markers such as natriuretic peptides or CA 125-5<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#44; or techniques such as body impedance&#44; lung ultrasound&#44; and inferior vena cava ultrasound<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#8211;7</span></a>&#46; The lack of sensitivity and specificity limit the utility of a physical examination and amino-terminal fraction of brain natriuretic peptide &#40;NT-proBNP&#41; determinations in the elderly population<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#44; though they continue to be the most commonly used tools in clinical practice&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The results of a subanalysis of clinical trials have recently been published which show the prognostic utility of peripheral edema and pulmonary rales in patients with heart failure with reduced left ventricular ejection fraction &#40;LVEF&#41;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a>&#46; The aim of this study was to evaluate the combined utility of a physical examination and NT-proBNP determination as markers of combined congestion in outpatients with heart failure in order to stratify their prognosis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This work is a descriptive&#44; observational&#44; retrospective study which analyzes data on patients with heart failure in follow-up between 2010 and 2018 in a specialized clinic within the Internal Medicine Department of the La Princesa University Hospital&#46; Patients were referred to the clinic following a hospital admission for heart failure &#40;both <span class="elsevierStyleItalic">de novo</span> and acute-on-chronic&#41; in the department itself or referred from other departments with the main reason being heart failure&#46; Consultations were provided by the same physician and treatment was provided in accordance with clinical guidelines&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0025" class="elsevierStylePara elsevierViewall">A complete physical examination and NT-proBNP determination were conducted at the initial or baseline visit&#46; A general blood test was done a few days before the consultation&#46; Data on overall mortality&#44; mortality due to heart failure&#44; and hospitalizations due to heart failure at one year from the baseline visit were gathered&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Clinical congestion was defined as absent &#40;no signs&#41; or present &#40;edema and&#47;or rales&#41;&#46; The presence of pulmonary rales was interpreted as positive when they were audible in at least the lower third of one or both lungs&#46; Peripheral edema was interpreted as positive when the patent presented with bilateral malleolar pitting&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Patients were classified into four groups based on the congestive pattern&#58; G1 &#40;no congestion&#41;&#44; G2 &#40;clinical congestion&#8239;&#43;&#8239;NT-proBNP &#60;1500&#8239;pg&#47;mL&#41;&#44; G3 &#40;no clinical congestion&#8239;&#43;&#8239;NT-proBNP &#8805;1500&#8239;pg&#47;mL or hemodynamic congestion&#41;&#44; and G4 &#40;clinical congestion and NT-proBNP &#8805;1500&#8239;pg&#47;mL or combined congestion&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Variables analyzed</span><p id="par0040" class="elsevierStylePara elsevierViewall">Demographic&#44; clinical &#40;number of prior hospitalizations due to heart failure&#44; recent hospital discharge due to heart failure &#40;from one to four months before the baseline visit&#41;&#44; and comorbidities&#41;&#44; analytical &#40;hemoglobin&#44; renal function parameters&#41;&#44; and echocardiographic &#40;left and right ventricular function&#44; left atrium size&#44; estimated pulmonary pressure&#41; variables were gathered&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The principal outcome measure was all-cause mortality and the secondary outcome measure was a composite outcome of death or hospitalization due to heart failure at one year from the initial visit&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Follow-up</span><p id="par0050" class="elsevierStylePara elsevierViewall">Patients had follow-up appointments at three&#44; six&#44; and 12 months from joining the clinic&#46; Appointments were able to be adjusted based on their clinical needs&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Quantitative variables are shown as means and standard deviation or as medians and interquartile range&#46; Qualitative variables are shown as absolute frequencies and percentages&#46; For quantitative variables&#44; comparisons between groups were made using Student&#39;s t test&#44; the Mann-Whitney U test&#44; the one-way ANOVA test&#44; and Tukey&#8217;s or the Games-Howell <span class="elsevierStyleItalic">post-hoc</span> test&#46; For qualitative variables&#44; comparisons between groups were made using the chi-square test&#44; using Haberman residuals or Fisher&#8217;s exact test when necessary&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Logistic regression models were calculated in order to study factors related to all-cause death and death&#47;hospitalization due to heart failure&#46; Variables which were associated with the outcome measures on a bivariate analysis were entered into the model as confounding variables&#46; Cox proportional-hazards models with the same confounding variables were used to study the time-to-event&#46; In addition&#44; the survival analysis was stratified according to whether the patient presented with reduced LVEF &#40;HFrEF&#41; &#40;LVEF&#8239;&#60;&#8239;40&#37;&#41;&#44; moderately reduced LVEF &#40;HFmrEF&#41; &#40;LVEF 40&#37; - 49&#37;&#41;&#44; or preserved LVEF &#40;HFpEF&#41; &#40;LVEF&#8239;&#8805;&#8239;50&#37;&#41;&#46; The survival curves of the different clinical and&#47;or hemodynamic congestion groups were compared within each LVEF group using the logrank test <span class="elsevierStyleItalic">p</span>-values less than 0&#46;05 were considered statistically significant&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">All analyses were conducted using the IBM SPSS 23&#46;0 statistical package &#40;Armonk&#44; NY&#59; USA&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Ethical considerations</span><p id="par0070" class="elsevierStylePara elsevierViewall">The ethical principles of the Declaration of Helsinki were followed and informed consent was requested from patients in order to participate in the study&#46; The protocol was approved by the Clinical Research Ethics Committee of the La Princesa University Hospital of Madrid&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Characteristics of the cohort</span><p id="par0075" class="elsevierStylePara elsevierViewall">The initial cohort comprised 341 patients&#46; Seven patients were lost to follow-up and 96 patients did not have NT-proBNP determinations at the start of follow-up&#46; Therefore&#44; an evaluation of combined clinical and hemodynamic congestion was able to be conducted in 238 patients&#44; which is this work&#8217;s study population&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The majority of patients were female &#40;148 &#40;61&#46;8&#37;&#41; women&#41; and elderly &#40;median age 83 years &#40;range&#58; 51-101&#41;&#41;&#46; The most frequent baseline cardiopathy was valvular and hypertensive heart disease&#46; Seventy percent had atrial fibrillation and 71&#46;6&#37; of patients presented with HFpEF&#46; A total of 43&#46;4&#37; of patients presented with severe pulmonary hypertension&#46; Eighty percent of patients were evaluated after a recent hospital discharge due to heart failure&#46; The mean estimated glomerular filtration rate &#40;eGFR&#41; was 52&#46;35&#8239;mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#46; A total of 77&#46;4&#37; of patients received treatment with ACE inhibitors&#47;ARBs&#44; 52&#37; took beta blockers&#44; and 9&#46;8&#37; of patients did not receive loop diuretics &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Congestion and prognosis</span><p id="par0085" class="elsevierStylePara elsevierViewall">The population was classified into four groups based on the physical examination and NT-proBNP levels&#58; 18&#37; were G1&#44; 21&#37; were G2&#44; 31&#37; were G3&#44; and 30&#37; were G4&#46; The differences between the population based on congestion are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In the first year of follow-up&#44; thirty patients &#40;12&#46;6&#37;&#41; died and 69 &#40;29&#37;&#41; died or were hospitalized due to heart failure&#46; The overall mortality rate varied based on the type of congestion&#58; the lowest mortality rate was in G1 &#40;4&#37;&#41; and the highest in G4 &#40;24&#37;&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Based on the findings of the univariable analysis&#44; the confounding variables of sex&#44; recent hospital discharge due to heart failure&#44; eGFR&#44; and LVEF were used on the multivariable analyses studying the relationship between combined congestion and the outcomes&#46; Combined congestion was the only independent factor associated with all-cause mortality &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;012&#41;&#46; Taking G1 as the reference group&#44; the risk of all-cause mortality was&#58; G2&#58; HR 4&#46;121 &#40;95&#37; CI 1&#46;131-15&#46;019&#41;&#59; G3&#58; HR 2&#46;511 &#40;95&#37; CI 1&#46;007-6&#46;263&#41;&#59; and G4&#58; HR 7&#46;418 &#40;95&#37; CI 1&#46;630-33&#46;763&#41;&#46; No significant differences were found between the G1 and G2 groups &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;183&#41; or the G1 and G3 groups &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;177&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Combined congestion was not significantly associated with death&#47;hospitalization due to heart failure whereas recent hospital discharge &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;027&#41; and baseline eGFR &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;038&#41; were&#46; Patients who started follow-up after a hospital discharge due to heart failure had a greater risk of death or hospitalization due to heart failure than patients without recent hospitalizations &#40;HR 2&#46;827 &#40;95&#37; CI 1&#46;170-6&#46;833&#41;&#41; whereas patients with an eGFR &#60;30 mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> had a risk of death&#47;hospitalization due to heart failure greater than patients with an eGFR &#8805;60&#8239;mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> &#40;HR 2&#46;723 &#40;95&#37; CI 1&#46;164-6&#46;347&#41;&#46; There were no significant differences between patients with an eGFR 30-60&#8239;mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> and patients with an eGFR &#8805;60&#8239;mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;650&#41; nor was there significant interaction among the variables &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;446&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">A shorter time to all-cause death was associated with the presence of combined congestion &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;007&#41;&#46; Risk of a faster time to death&#44; taking G1 as the reference group&#44; was&#58; G2&#58; HR 3&#46;909 &#40;95&#37; CI 1&#46;145-13&#46;347&#41;&#59; G3&#58; HR 2&#46;380 &#40;95&#37; CI 1&#46;027-5&#46;517&#41;&#59; and G4&#58; HR 7&#46;460 &#40;95&#37; CI 1&#46;717-32&#46;406&#41;&#46; No significant differences were found between the G1 and G2 groups &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;149&#41; or the G1 and G3 groups &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;479&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">A survival analysis was conducted after stratifying the baseline LVEF into three categories&#46; The survival curves for all-cause mortality &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; and mortality or hospitalization due to heart failure &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; are shown for each group of patients&#46; No differences were observed in all-cause mortality based on LVEF&#46; However&#44; a significantly greater rate of death or hospitalization due to heart failure was observed in patients in G4 vs&#46; G3&#44; with a baseline LVEF&#8239;&#60;&#8239;40&#37; &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;027&#41;&#46; A similar trend was observed between G1 vs&#46; G4 and G2 vs&#46; G4&#46; Therefore&#44; another logistic regression analysis was conducted&#44; with patients without congestion in one group and patients with one type of congestion in another&#58; G1 &#43; G2 &#43; G3&#46; It was found that risk of death or hospitalization due to heart failure was two times higher in G4 &#40;HR 2&#46;167 &#40;95&#37; CI 1&#46;174-4&#46;002&#41;&#41; than in G1 &#43; G2 &#43; G3&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">LVEF was not significantly associated with the composite variable of death or hospitalization due to heart failure &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;365&#41;&#46; On the survival analysis&#44; the time to death or hospitalization due to heart failure was significantly less in G4 &#40;estimated mean 13&#46;8 months &#40;95&#37; CI 12&#46;0-15&#46;6&#41;&#41; than in patients in G1 &#43; G2 &#43; G3 &#40;estimated mean 16&#46;5 months &#40;95&#37; CI 15&#46;6-17&#46;5&#41;&#41; &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;009&#41;&#46; On the analysis stratified by LVEF&#44; the G4 group took less time to reach the outcome of death&#47;hospitalization due to heart failure in both HFrEF patients &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;028&#41; and HFpEF patients &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;041&#41;&#44; but not in HFmrEF patients &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;869&#41;&#46; The survival curves are shown in <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">In elderly patients with heart failure in outpatient follow-up&#44; combined clinical and hemodynamic congestion is a predictive factor of overall mortality and mortality or hospitalization due to heart failure&#46; Recent hospital discharge and kidney failure are also associated with the composite variable of hospitalization&#47;death due to heart failure&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In this study&#44; 30&#37; of patients presented with combined congestion and 52&#37; with one type of congestion &#40;either clinical or hemodynamic congestion&#41;&#46; Congestion has been identified as a prognostic factor in heart failure&#44; fundamentally in the context of acute decompensation&#44; both upon hospital admission<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and discharge<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In order to overcome the limitations of a physical examination&#44; scales have been developed that include various signs and symptoms of congestion&#46; They are based on works that analyzed cohorts that are different from the one studied in this work&#46; In those studies&#44; 70&#37;-80&#37; of patients were males aged between 51 to 68 years with mean LVEF of 20&#37;-36&#37;&#44; mostly ischemic etiology&#44; and patients were studied in the contest of hospital discharge or early outpatient monitoring<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;11&#8211;13</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Some of these scales contain multiple variables&#44; including the evaluation of jugular venous distention&#44; which entails technical and interpretation limitations<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#44; while patients with advanced kidney failure or severe valvular disease tend to be excluded&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In regard to natriuretic peptides&#44; elevated NT-proBNP levels upon discharge following hospitalization due to acute heart failure or lack of a decline in these levels during hospitalization is correlated with a worse short-term prognosis<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; Natriuretic peptide levels correlate with the severity of congestion&#44; with values &#62;1500-3000 pg&#47;mL indicating moderate-severe congestion<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; However&#44; in the context of chronic heart failure&#44; treatment guided by natriuretic peptides has not demonstrated better outcomes in terms of mortality or readmissions compared to clinical management&#44; especially in patients older than 75 years<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The majority of studies show that the benefits of treatment guided by NT-proBNP have been observed only in patients with HFrEF and that comorbidities explain the lower predictive capacity of natriuretic peptides in elderly patients<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; Nevertheless&#44; Rubio-Gracia et al&#46; have recently shown how very high NT-proBNP levels upon hospital discharge were independent predictors of overall mortality at one year of follow-up in a specialized heart failure clinic in patients with a very similar profile to those described in this work<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Among outpatients&#44; Curbelo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#44; who are investigators from our group&#44; have shown the prognostic utility of the combined use of natriuretic peptides&#44; inferior vena cava and lung ultrasound&#44; and bioimpedance in patients with chronic heart failure&#46; However&#44; in both works&#44; the NT-proBNP cut-off point was higher than that of this work and the ultrasound techniques are often not accessible and require training&#46; In our study&#44; only the presence of combined congestion was an independent risk factor for all-cause mortality&#44; with a seven-fold increase in risk compared to patients without congestion&#46; The risk of death or hospitalization due to heart failure was twice as high in patients with combined congestion compared to patients without congestion or with one type of congestion&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">These results are comparable to those of the cohort studied by Damy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> in which overall mortality increased with greater congestion&#58; the rate was 5&#46;1&#37; in patients without congestion and 23&#46;1&#37; in patients who presented with cardiac congestion in the right and left chambers&#46; In a <span class="elsevierStyleItalic">post-hoc</span> analysis of the AF-CHF &#40;Atrial Fibrillation and Chronic Heart Failure&#41; study&#44; the four congestive signs evaluated &#40;jugular venous distention&#44; third heart sound&#44; peripheral edema&#44; and pulmonary rales&#41; provided prognostic information&#44; though only the latter two were associated with cardiovascular mortality<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46; Elevated NT-proBNP levels &#40;&#8805;1000 pg&#47;mL&#41; have also been associated with a worse prognosis&#44; especially in elderly outpatients with HFrEF or HFmrEF<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">In previous works on the elderly population hospitalized due to heart failure&#44; no differences in prognosis have been observed based on LVEF<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; The clinical signs and echocardiographic parameters of congestion do not differ between HFrEF vs&#46; HFpEF&#44; though lower NT-proBNP values have been described in HFpEF<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#46; In our study&#44; overall mortality did not differ based on LVEF&#46; Death or hospitalization due to heart failure occurred earlier in patients with combined congestion than in the rest of patients in all LVEF group except for patients with HFmrEF&#44; though this effect could be due to the smaller size of that group&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">It is important to highlight that patients with combined congestion had various characteristics associated with a worse prognosis&#58; male sex<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#44; recent hospital discharge<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#44; kidney failure<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;26</span></a>&#44; presence of right ventricular dysfunction or pulmonary hypertension<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> or growth of the left atrium<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#44; low blood pressure or hemoglobin values<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#44; and treatment with high doses of furosemide<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;31</span></a>&#46;</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Limitations and strengths</span><p id="par0170" class="elsevierStylePara elsevierViewall">This is a retrospective study conducted in a single center&#46; The echocardiogram was conducted in the context of daily clinical practice and the parameters included were those from the date closest to the date of inclusion in the registry&#59; data on diastolic function were not able to be included&#46; Data on dependency&#44; frailty&#44; nutritional status&#44; or body mass index&#44; which could be linked to mortality in this population&#44; were also not gathered&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Physical examination data were gathered without independent supervision&#46; Data on changes in treatment at six months of follow-up were also not collected&#46; It is necessary to conduct a larger study in order to demonstrate differences in the composite heart failure outcome in the HFmrEF group&#46; On the other hand&#44; the data obtained are from real-world patients and provide evidence in a field of study in which many uncertainties remain&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">In conclusion&#44; a physical examination and NT-proBNP determination were shown to be useful when combined for identifying outpatients with heart failure&#44; both HFrEF and HFpEF&#44; who have a worse prognosis&#46; The identification of this profile of high-risk patients should lead to a review of the suitability of the treatment and a closer monitoring strategy when planning follow-up in order to try to improve the prognosis&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of interest</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors declare that they do not have any conflicts of interest&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Funding</span><p id="par0190" class="elsevierStylePara elsevierViewall">This work has not received any type of funding&#46;</p></span></span>"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">This work aims to evaluate whether a clinical examination and measurement of N-terminal pro-brain natriuretic peptide can predict poor prognosis in outpatients with heart failure&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">We carried out a retrospective study from 2010 to 2018 in 238 patients diagnosed with heart failure&#46; At baseline&#44; we evaluated the presence of pulmonary rales and bilateral leg edema &#40;clinical congestion&#41; together with N-terminal pro-brain natriuretic peptide &#8805; 1500 pg&#47;mL &#40;hemodynamic congestion&#41;&#46; Patients were classified into 4 groups depending on their congestion pattern&#58; no congestion &#40;G1&#41; &#40;n &#61; 50&#41;&#59; clinical congestion &#40;G2&#41; &#40;n &#61; 43&#41;&#59; hemodynamic congestion &#40;G3&#41; &#40;n &#61; 73&#41;&#59; and clinical and hemodynamic congestion &#40;G4&#41; &#40;n &#61; 72&#41;&#46; The primary outcome was all-cause mortality at one year of follow-up&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">A total of 238 patients were included&#46; The mean age was 82 years&#44; 61&#46;8&#37; were women&#44; and 20&#46;7&#37; had reduced left ventricular ejection fraction&#46; Thirty patients died in the first year of follow-up &#40;12&#46;6&#37;&#41;&#46; After controlling for confounding variables &#40;sex&#44; recent discharge for heart failure&#44; estimated glomerular filtration rate&#44; and left ventricular ejection fraction&#41;&#44; the independent risk of death in each group compared to G1 as the reference group was&#58; G2&#58; HR 4&#46;121 &#40;95&#37;CI 1&#46;131-15&#46;019&#41;&#59; G3&#58; HR 2&#46;511 &#40;95&#37;CI 1&#46;007-6&#46;263&#41;&#59; and G4&#58; HR 7&#46;418 &#40;95&#37;CI 1&#46;630-33&#46;763&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Congestion in outpatients with heart failure correlates with prognosis&#46; Patients with both clinical and hemodynamic congestion had the highest risk of all-cause death at one year&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Patients and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
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        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">El objetivo del estudio fue evaluar si la exploraci&#243;n f&#237;sica y la determinaci&#243;n de la fracci&#243;n N-terminal del prop&#233;ptido natriur&#233;tico cerebral pueden predecir un peor pron&#243;stico en pacientes ambulatorios con insuficiencia card&#237;aca&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo llevado a cabo entre 2010 y 2018&#44; en 238 pacientes diagnosticados de insuficiencia card&#237;aca&#46; Al inicio&#44; se evalu&#243; la presencia de crepitantes pulmonares y edema de miembros inferiores &#40;congesti&#243;n cl&#237;nica&#41; junto con la fracci&#243;n N-terminal del prop&#233;ptido natriur&#233;tico cerebral &#8805; 1500 pg&#47;mL &#40;congesti&#243;n hemodin&#225;mica&#41;&#46; Los pacientes se clasificaron en 4 grupos en funci&#243;n del patr&#243;n congestivo&#58; sin congesti&#243;n &#40;G1&#41; &#40;n &#61; 50&#41;&#59; con congesti&#243;n cl&#237;nica &#40;G2&#41; &#40;n &#61; 43&#41;&#59; con congesti&#243;n hemodin&#225;mica &#40;G3&#41; &#40;n &#61; 73&#41; y con congesti&#243;n cl&#237;nica y hemodin&#225;mica &#40;G4&#41; &#40;n &#61; 72&#41;&#46; El objetivo primario fue la muerte por cualquier causa al a&#241;o de seguimiento&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Se analizaron un total de 238 pacientes&#44; edad media 82 a&#241;os&#44; 61&#44;8&#37; mujeres&#44; y 20&#44;7&#37; con fracci&#243;n de eyecci&#243;n del ventr&#237;culo izquierdo reducida&#46; Treinta pacientes &#40;12&#44;6&#37;&#41; fallecieron en el primer a&#241;o de seguimiento&#46; Despu&#233;s de ajustar por variables de confusi&#243;n &#40;sexo&#44; alta hospitalaria reciente por insuficiencia card&#237;aca&#44; filtrado glomerular estimado&#44; y fracci&#243;n de eyecci&#243;n del ventr&#237;culo izquierdo&#41;&#44; el riesgo de muerte en cada grupo&#44;al compararlos con el grupo de referencia G1&#44; fue&#58; G2&#44; HR 4&#44;121 &#40;IC95&#37; 1&#44;131&#8211;15&#44;019&#41;&#59; G3&#44; HR 2&#44;511 &#40;IC95&#37; 1&#44;007-6&#44;263&#41;&#44; y&#59; G4&#44; HR 7&#44;418 &#40;IC95&#37; 1&#44;630-33&#44;763&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">La congesti&#243;n en pacientes ambulatorios con insuficiencia card&#237;aca se correlaciona con el pron&#243;stico&#46; Los pacientes con congesti&#243;n cl&#237;nica y hemodin&#225;mica tuvieron el mayor riesgo de muerte global al a&#241;o&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Pacientes y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
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      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Gil-Mart&#237;nez P&#44; Curbelo J&#44; Roy-Vallejo E&#44; Mesado-Mart&#237;nez D&#44; Ciudad-Sa&#241;udo M&#44; Su&#225;rez-Fern&#225;ndez C&#46; Evaluaci&#243;n del grado de congesti&#243;n cl&#237;nica y hemodin&#225;mica como predictores de mortalidad en pacientes ambulatorios con insuficiencia card&#237;aca de edad avanzada&#46; Rev Clin Esp&#46; 2022&#59;222&#58;377&#8211;384&#46;</p>"
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      0 => array:8 [
        "identificador" => "fig0005"
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        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Survival curve for the outcome of all-cause mortality based on clinical and&#47;or hemodynamic congestion and LVEF&#46; Kaplan-Meier survival analysis for the primary outcome of overall mortality according to presence of congestion in the groups&#58; &#40;G1&#41; No clinical congestion&#8239;&#43;&#8239;NT-proBNP &#60;1500&#59; &#40;G2&#41; Clinical congestion&#8239;&#43;&#8239;NT-proBNP &#60;1500&#59; &#40;G3&#41; No clinical congestion&#8239;&#43;&#8239;NT-proBNP &#8805;1500&#59; &#40;G4&#41; Clinical congestion&#8239;&#43;&#8239;NT-proBNP &#8805;1500 and left ventricle ejection fraction &#40;LVEF&#41; categories of &#60;40&#37;&#44; 40&#37; - 50&#37;&#44; and &#8805;50&#37;&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Survival curve for the outcome of death&#47;hospitalization due to HF based on clinical and&#47;or hemodynamic congestion and LVEF&#46; Kaplan-Meier survival curves for the outcome of death&#47;hospitalization due to HF according to presence of congestion in the groups&#58; &#40;G1&#41; No clinical congestion&#8239;&#43;&#8239;NT-proBNP &#60;1500&#59; &#40;G2&#41; Clinical congestion&#8239;&#43;&#8239;NT-proBNP &#60;1500&#59; &#40;G3&#41; No clinical congestion&#8239;&#43;&#8239;NT-proBNP &#8805;1500&#59; &#40;G4&#41; Clinical congestion&#8239;&#43;&#8239;NT-proBNP &#8805;1500 and left ventricle ejection fraction &#40;LVEF&#41; categories of &#60;40&#37;&#44; 40&#37; - 50&#37;&#44; and &#8805;50&#37;&#46;</p>"
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        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
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          0 => array:3 [
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Survival curve for the outcome of death&#47;hospitalization due to HF based on congestion regrouped into two categories &#40;with&#47;without combined congestion&#41; and LVEF&#46; Kaplan-Meier survival curves for the outcome of death&#47;hospitalization due to HF according to presence of congestion in the groups&#58; &#40;G1&#8239;&#43;&#8239;G2 &#43; G3&#41;&#58; one type of congestion or no congestion and &#40;G4&#41; combined or mixed congestion and the left ventricular ejection fraction &#40;LVEF&#41; categories &#60;40&#37;&#44; 40&#37; - 49&#37;&#44; and &#8805;50&#37;&#46;</p>"
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      3 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">ACE inhibitors&#58; angiotensin-converting enzyme inhibitors&#59; ARB&#58; angiotensin-2 receptor blockers&#59; COPD&#58; chronic obstructive pulmonary disease&#59; DBP&#58; diastolic blood pressure&#59; DM&#58; diabetes mellitus&#59; eGFR&#58; estimated glomerular filtration rate&#59; HF&#58; heart failure&#59; HT&#58; hypertension&#59; LA&#58; left atrium&#59; LVEF&#58; left ventricular ejection fraction&#59; NYHA&#58; New York Heart Association&#59; PASP&#58; pulmonary artery systolic pressure&#59; SBP&#58; systolic blood pressure&#59; TAPSE&#58; tricuspid annulus planar systolic excursion&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Groups based on congestion&#58; &#40;G1&#41; No clinical congestion&#8239;&#43;&#8239;NT-proBNP &#60;1500&#59; &#40;G2&#41; Clinical congestion&#8239;&#43;&#8239;NT-proBNP &#60;1500&#59; &#40;G3&#41; No clinical congestion&#8239;&#43;&#8239;NT-proBNP &#8805;1500&#59; &#40;G4&#41; Clinical congestion&#8239;&#43;&#8239;NT-proBNP &#8805;1500&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Quantitative variables are shown as mean and standard deviation&#46; Quantitative variables are shown as number &#40;n&#41; and percentage &#40;&#37;&#41;&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Post-hoc</span> comparison with Tukey&#8217;s or the Games-Howell test&#58; statistical significance at a level of 0&#46;05 with&#58; <span class="elsevierStyleSup">a</span> G1&#59; <span class="elsevierStyleSup">b</span> G2&#59; <span class="elsevierStyleSup">c</span> G3&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">&#8593;&#8595;Corrected standardized residuals&#46; Boxes that have absolute frequencies significantly higher &#40;&#8593;&#41; or lower &#40;&#8595;&#41; than 0&#46;05 than what was expected under the independence hypothesis&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleBold">Female sex</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">148 &#40;61&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">41 &#40;82&#46;0&#37;&#41;&#8593;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;21&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">21 &#40;31&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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Journal Information
Vol. 222. Issue 7.
Pages 377-384 (August - September 2022)
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Vol. 222. Issue 7.
Pages 377-384 (August - September 2022)
Original article
Assessment of clinical and hemodynamic congestion as predictors of mortality in elderly outpatients with heart failure
Evaluación del grado de congestión clínica y hemodinámica como predictores de mortalidad en pacientes ambulatorios con insuficiencia cardíaca de edad avanzada
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P. Gil-Martíneza,b,
Corresponding author
pgmart@yahoo.com

Corresponding author.
, J. Curbeloa,b, E. Roy-Vallejoa,b, D. Mesado-Martínezb,c, M. Ciudad-Sañudoa, C. Suárez-Fernándeza
a Servicio de Medicina Interna, Hospital Universitario de la Princesa. Fundación Investigación Biosanitaria del Hospital de la Princesa, Madrid, Spain
b Grupo de trabajo de Insuficiencia Cardíaca de la Sociedad Española de Medicina Interna, Madrid, Spain
c Servicio de Medicina Interna, Hospital Universitario General de Villalba, Villalba, Madrid, Spain
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Abstract
Introduction

This work aims to evaluate whether a clinical examination and measurement of N-terminal pro-brain natriuretic peptide can predict poor prognosis in outpatients with heart failure.

Patients and methods

We carried out a retrospective study from 2010 to 2018 in 238 patients diagnosed with heart failure. At baseline, we evaluated the presence of pulmonary rales and bilateral leg edema (clinical congestion) together with N-terminal pro-brain natriuretic peptide ≥ 1500 pg/mL (hemodynamic congestion). Patients were classified into 4 groups depending on their congestion pattern: no congestion (G1) (n = 50); clinical congestion (G2) (n = 43); hemodynamic congestion (G3) (n = 73); and clinical and hemodynamic congestion (G4) (n = 72). The primary outcome was all-cause mortality at one year of follow-up.

Results

A total of 238 patients were included. The mean age was 82 years, 61.8% were women, and 20.7% had reduced left ventricular ejection fraction. Thirty patients died in the first year of follow-up (12.6%). After controlling for confounding variables (sex, recent discharge for heart failure, estimated glomerular filtration rate, and left ventricular ejection fraction), the independent risk of death in each group compared to G1 as the reference group was: G2: HR 4.121 (95%CI 1.131-15.019); G3: HR 2.511 (95%CI 1.007-6.263); and G4: HR 7.418 (95%CI 1.630-33.763).

Conclusion

Congestion in outpatients with heart failure correlates with prognosis. Patients with both clinical and hemodynamic congestion had the highest risk of all-cause death at one year.

Keywords:
Congestion
Heart failure
Admission
Mortality
Resumen
Introducción

El objetivo del estudio fue evaluar si la exploración física y la determinación de la fracción N-terminal del propéptido natriurético cerebral pueden predecir un peor pronóstico en pacientes ambulatorios con insuficiencia cardíaca.

Pacientes y métodos

Estudio retrospectivo llevado a cabo entre 2010 y 2018, en 238 pacientes diagnosticados de insuficiencia cardíaca. Al inicio, se evaluó la presencia de crepitantes pulmonares y edema de miembros inferiores (congestión clínica) junto con la fracción N-terminal del propéptido natriurético cerebral ≥ 1500 pg/mL (congestión hemodinámica). Los pacientes se clasificaron en 4 grupos en función del patrón congestivo: sin congestión (G1) (n = 50); con congestión clínica (G2) (n = 43); con congestión hemodinámica (G3) (n = 73) y con congestión clínica y hemodinámica (G4) (n = 72). El objetivo primario fue la muerte por cualquier causa al año de seguimiento.

Resultados

Se analizaron un total de 238 pacientes, edad media 82 años, 61,8% mujeres, y 20,7% con fracción de eyección del ventrículo izquierdo reducida. Treinta pacientes (12,6%) fallecieron en el primer año de seguimiento. Después de ajustar por variables de confusión (sexo, alta hospitalaria reciente por insuficiencia cardíaca, filtrado glomerular estimado, y fracción de eyección del ventrículo izquierdo), el riesgo de muerte en cada grupo,al compararlos con el grupo de referencia G1, fue: G2, HR 4,121 (IC95% 1,131–15,019); G3, HR 2,511 (IC95% 1,007-6,263), y; G4, HR 7,418 (IC95% 1,630-33,763).

Conclusión

La congestión en pacientes ambulatorios con insuficiencia cardíaca se correlaciona con el pronóstico. Los pacientes con congestión clínica y hemodinámica tuvieron el mayor riesgo de muerte global al año.

Palabras clave:
Congestión
Insuficiencia cardíaca
Ingreso
Mortalidad

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