Inotropes and cardiorenal syndrome in acute heart failure – A retrospective comparative analysis | Revista Portuguesa de Cardiologia (English edition)

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comparativa retrospetiva" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 702 "Ancho" => 2578 "Tamanyo" => 91401 ] ] "descripcion" => array:1 [ "en" => "Changes in renal function parameters during hospitalization. eGFR: estimated glomerular filtration rate." ] ] ] "textoCompleto" => "IntroductionAcute heart failure (AHF) remains the single most common admitting diagnosis in industrialized countries, despite significant advances in pharmacologic and device therapy.<a class="elsevierStyleCrossRefs" href="#bib0185">1,2</a> Some degree of renal impairment is present in more than a third of patients with AHF, associated with reduction in renal blood flow and/or elevation in central venous pressure, leading to a decrease in estimated glomerular filtration rate (eGFR).<a class="elsevierStyleCrossRefs" href="#bib0195">3–5</a> Conversely, renal impairment itself may predispose to worsening heart failure (HF), through constant salt and water retention, diuretic resistance and neurohormonal activation, leading to increased cardiac workload.<a class="elsevierStyleCrossRefs" href="#bib0210">6,7</a> In a broad spectrum of patients with chronic HF in the CHARM study,<a class="elsevierStyleCrossRef" href="#bib0220">8</a> renal dysfunction was independently associated with increased risk of death, cardiovascular death, and hospitalization due to AHF.<a class="elsevierStyleCrossRef" href="#bib0225">9</a> Furthermore, in advanced chronic HF, renal impairment was a stronger predictor of mortality than either left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) functional class.<a class="elsevierStyleCrossRef" href="#bib0230">10</a>Both dobutamine and levosimendan are inotropic drugs, used specifically to improve cardiac contractility.<a class="elsevierStyleCrossRef" href="#bib0235">11</a> Through activation of ATP-sensitive potassium channels, levosimendan causes both arterial and venous vasodilation (mainly the latter).<a class="elsevierStyleCrossRef" href="#bib0235">11</a> This additional effect of levosimendan over dobutamine may be crucial in AHF, since central venous pressure is an independent predictor of cardiorenal syndrome (CRS) in this setting.<a class="elsevierStyleCrossRef" href="#bib0240">12</a>However, only a few studies comparing the effects of levosimendan with dobutamine on renal function in patients hospitalized with AHF have been published.<a class="elsevierStyleCrossRefs" href="#bib0245">13,14</a>We aimed to assess the incidence of CRS according to the inotrope used and to determine its predictors in order to identify patients who could benefit from the most renoprotective inotrope.The primary endpoint was CRS incidence during hospital stay. The secondary endpoints were recovery of eGFR at discharge, readmission for AHF and mortality during follow-up.MethodsPopulation and study designWe retrospectively studied 108 consecutive patients admitted between May 2009 and March 2014 to a single cardiac intensive care unit for AHF with symptoms or signs of severe congestion or low cardiac output requiring inotropes. The diagnosis of AHF was established according to the current European Society of Cardiology guidelines.<a class="elsevierStyleCrossRef" href="#bib0255">15</a>Patients with end-stage renal disease on a regular program of renal replacement therapy were excluded.The sample was divided into two groups according to the inotrope used (levosimendan or dobutamine), prescribed at the discretion of the admitting physician. In the levosimendan group no initial bolus was given and perfusion was started at 0.1 μg/kg/min and titrated up to 0.2 μg/kg/min if tolerated. In the dobutamine group perfusion was started at 5.0 μg/kg/min and titrated on a clinical basis.CRS was defined as an increase of ≥26.5 μmol/l in serum creatinine relative to the admission value.<a class="elsevierStyleCrossRef" href="#bib0260">16</a> The Modification of Diet in Renal Disease (MDRD) equation was used to calculate eGFR, according to the recommendations of the KDIGO Clinical Practice Guideline for Acute Kidney Injury.<a class="elsevierStyleCrossRef" href="#bib0265">17</a> Changes in renal function were assessed by determining maximum and discharge creatinine and blood urea nitrogen (BUN) and minimum eGFR.The study is in accordance with the principles outlined in the Declaration of Helsinki.Data collectionBaseline data were collected from patients’ medical records and included previous medical history (time course and etiology of HF, ischemic heart disease, hypertension, diabetes and chronic renal failure and current therapy), physical examination at admission (heart rate and blood pressure), electrocardiogram and blood test analysis (creatinine, BUN, ionogram, N-terminal pro-B-type natriuretic peptide [NT-pro-BNP], hemoglobin, total bilirubin, alkaline phosphatase, aspartate transaminase [AST], alanine transaminase [ALT] and cystatin C).All patients underwent transthoracic echocardiography with assessment of both systolic (LVEF by the modified Simpson's rule) and diastolic function.Therapies analyzed were maximum daily dose of furosemide and type of administration (bolus vs. perfusion), use of vasodilator doses of dopamine and noradrenaline, renal support therapy and noninvasive or invasive mechanical ventilation.In-hospital mortality and length of hospital stay were analyzed.Readmission for AHF and mortality during follow-up were also obtained from clinical records from outpatient clinic, hospital ward and emergency department admissions and through phone calls for patients not followed at our hospital.Statistical analysisThe statistical analysis was performed with SPSS version 21.0 (IBM SPSS Inc., Chicago, IL, USA).Data were summarized using means, standard errors, numbers and percentages, as appropriate. The chi-square test was used for dichotomous variables and the independent-samples t test for continuous variables with normal distribution. Multivariate analysis was used to determine predictors of CRS and in-hospital mortality. Statistical significance was defined as p<0.05.ResultsPatient characteristicsOne hundred and eight consecutive patients admitted to our cardiac intensive care unit with AHF were studied. Mean age was 66±15 years and 74% were male. According to the decision of the admitting physician, 77 patients (71%) were treated with levosimendan and the remaining 31 (29%) with dobutamine.Comparison of baseline characteristics and therapeutic strategiesPatients in the levosimendan group were younger and more frequently male.No differences were found between the groups in HF etiology (ischemic vs. non-ischemic) or previous history of coronary artery disease, hypertension, diabetes or chronic kidney disease. In both groups, the incidence of new-onset HF was similar. The most frequent precipitating factor (acute coronary syndrome: 35% vs. 55%, p=0.06) was similar in both groups, as were atrial fibrillation incidence at admission and previous use of beta-blockers. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> presents the details of the above data.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> summarizes the main clinical, laboratory and echocardiographic data at admission. Systolic blood pressure and hemoglobin were lower in the dobutamine group and total bilirubin was higher in the levosimendan group, but there were no differences in sodium, potassium, alkaline phosphatase, AST or ALT. LVEF was lower in the levosimendan group, with no differences between groups regarding prevalence of diastolic dysfunction.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the main differences in treatment between the groups. There were no differences in maximum daily dose of furosemide or its form of administration (bolus vs. infusion). The use of intra-aortic balloon-pump counterpulsation and urgent revascularization was similar between groups. Noradrenaline and dopamine in vasodilator doses were more frequent in the dobutamine group, as was the need for renal support therapy and mechanical ventilation.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Primary and secondary endpointsThe dobutamine group had a higher incidence of the primary endpoint of CRS (49% vs. 77%, p<0.01) and lower minimum eGFR (44±22 vs. 31±18 ml/min/1.73 m2, p<0.01).Furthermore, the percentage of decrease in eGFR during hospital stay was higher in the dobutamine group than in the levosimendan group (24±21% vs. 38±28%, p=0.02).At discharge, patients who received dobutamine presented a trend towards partial recovery in renal function (eGFR 56±28 ml/min/1.73 m2 at admission vs. 45±25 ml/min/1.73 m2 at discharge, p=0.06), unlike patients treated with levosimendan (eGFR 61±30 ml/min/1.73 m2 at admission vs. 60±27 ml/min/1.73 m2 at discharge, p=0.67).Changes in renal function parameters are represented in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Using logistic regression analysis, which included all variables that differed between the groups, cystatin C (odds ratio [OR] 8.6, 95% confidence interval [CI] 1.8-40.7, p=0.007) was identified as the only predictor for CRS development during hospital stay (p=0.73 for the Hosmer-Lemeshow test).In-hospital prognosisLength of stay was similar in both groups (10±8 vs. 12±9 days, p=0.29). In-hospital mortality (19%) was higher in the dobutamine group (9% vs. 42%, p<0.01). CRS (OR 13, 95% CI 1.5-114.4, p=0.02) and the inotrope used (OR for dobutamine 5, 95% CI 1.47-19.92, p=0.01) were independent predictors of mortality.Follow-upDuring follow-up (481±365 days), 44 patients were readmitted due to AHF and 39 died. There were no differences between the groups regarding mortality (41% vs. 56%, p=0.28), readmission due to AHF (47% vs. 61%, p=0.29), or the composite endpoint of death and readmission due to AHF (64% vs. 67%, p=0.85).DiscussionRenal dysfunction is one of the most important and prevalent comorbidities of HF and has emerged as a critical risk factor for prolonged hospitalization and rehospitalization and short- and long-term mortality in patients with AHF.<a class="elsevierStyleCrossRef" href="#bib0270">18</a> The prevalence of CRS in our study was very high in both groups (49% and 77%) (although similar to that reported in a sub-analysis of the ADHERE database<a class="elsevierStyleCrossRef" href="#bib0200">4</a>), and was an independent predictor of mortality, associated with a risk of death thirteen times higher than in those who did not develop CRS. The high prevalence of acute kidney injury might be explained by the characteristics of our study population, since we only included patients who required treatment with inotropes, which is a surrogate marker of low cardiac output. Factors such as age (mainly elderly) and high incidences of hypertension, diabetes and coronary artery disease, all of them recognized contributors to renal dysfunction, may also have had an impact.<a class="elsevierStyleCrossRef" href="#bib0200">4</a>Unfortunately, the clinical management of CRS is largely empirical and many drugs traditionally used to treat HF (diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists) may result in renal dysfunction due to their serious side effects, especially following inappropriate or excessive use.<a class="elsevierStyleCrossRefs" href="#bib0275">19,20</a>Levosimendan is a positive inotropic drug with vasodilatory properties that has been assessed in several clinical studies in patients with AHF, which demonstrated improvements in renal hemodynamics and laboratory markers of renal function.<a class="elsevierStyleCrossRefs" href="#bib0245">13,14,21–24</a> However, there are few studies comparing the renoprotective profile of levosimendan with that of dobutamine in patients with AHF.<a class="elsevierStyleCrossRefs" href="#bib0245">13,14</a> The randomized controlled LIDO trial<a class="elsevierStyleCrossRef" href="#bib0285">21</a> reported a significant reduction of 9% in creatinine level in patients with almost normal renal function when treated with levosimendan as opposed to dobutamine. In patients with moderate renal impairment, levosimendan was found to have a more robust effect on eGFR, with an increase of 45% at 72 hours, compared with dobutamine infusion.<a class="elsevierStyleCrossRef" href="#bib0285">21</a> Similarly, the nonrandomized PORTLAND study<a class="elsevierStyleCrossRef" href="#bib0290">22</a> assessed the efficacy and safety of levosimendan in the treatment of AHF in everyday clinical practice. There was rapid improvement in diuresis in previously oliguric patients after beginning levosimendan, along with a reduction in serum creatinine levels that persisted at five days.<a class="elsevierStyleCrossRef" href="#bib0290">22</a> Yilmaz et al.<a class="elsevierStyleCrossRef" href="#bib0245">13</a> investigated 88 consecutive patients with AHF (NYHA class III-IV) who required inotropic therapy. Patients were randomized to receive either levosimendan or dobutamine. While LVEF increased significantly in both treatment groups, the levosimendan group showed significant improvement in eGFR after 24 hours (+15.3%), while the dobutamine arm showed no difference (-1.33%).<a class="elsevierStyleCrossRef" href="#bib0245">13</a> The same group also compared the effects of levosimendan and dobutamine on right ventricular function in 40 consecutive patients with severe chronic biventricular dysfunction and showed that right ventricular function improved more in patients receiving levosimendan.<a class="elsevierStyleCrossRef" href="#bib0250">14</a> Furthermore, in these patients levosimendan improved both 24-hour urine output and creatinine levels, whereas dobutamine produced only a small increase in urine output and no decrease in creatinine levels.<a class="elsevierStyleCrossRef" href="#bib0250">14</a> The beneficial effect of levosimendan on renal function extends beyond AHF, according to two recent meta-analyses, in acute critically ill patients and in the perioperative setting, that showed a reduction in kidney injury.<a class="elsevierStyleCrossRefs" href="#bib0305">25,26</a>In agreement with these findings, our study, which aims to describe a real-world AHF population, showed that, even though eGFR was similar in the two groups at admission, patients treated with levosimendan had a lower incidence of CRS (49% vs. 77%). Furthermore, renal function recovery at discharge was incomplete in individuals who received dobutamine, unlike in patients selected for levosimendan perfusion, who had a complete recovery.The mechanisms underlying levosimendan's renoprotective effect in patients with AHF are not fully understood. Improved hemodynamics, and hence increased kidney perfusion, could play an important role.<a class="elsevierStyleCrossRef" href="#bib0300">24</a> However, in multivariate analysis, levosimendan therapy was shown to predict improved renal function independently of changes in left ventricular performance, suggesting that other factors may be responsible.<a class="elsevierStyleCrossRef" href="#bib0295">23</a> Different possible renoprotective mechanisms of levosimendan have been proposed: an increase in renal blood flow due to hemodynamic improvement,<a class="elsevierStyleCrossRefs" href="#bib0315">27,28</a> additional increases in renal perfusion via vasodilation through KATP channel agonism,<a class="elsevierStyleCrossRef" href="#bib0325">29</a> reversal of AT-2-mediated mesangial cell contraction with a consequent increase in glomerular capillary surface area and glomerular filtration rate,<a class="elsevierStyleCrossRef" href="#bib0300">24</a> and possible anti-inflammatory properties, suggesting that it may protect against tubular injury.<a class="elsevierStyleCrossRef" href="#bib0330">30</a> However, systemic venodilation together with pulmonary vasodilation, improving right ventricular performance, is probably the main mechanism distinguishing the effect on renal function of this drug from that of dobutamine.<a class="elsevierStyleCrossRef" href="#bib0245">13</a> Moreover, the formation of an active metabolite of levosimendan may account for the prolonged effect of this drug.<a class="elsevierStyleCrossRef" href="#bib0335">31</a>Nevertheless, in our study some differences between the groups may preclude firm conclusions. Patients in the dobutamine group appeared to present in a more severe condition, as expressed by lower systolic blood pressure, lower hemoglobin levels and older age, and generally requiring more multi-organ support. On the other hand, lower systolic blood pressure may itself have influenced the choice of the inotrope by the admitting physician, since the hypotensive effect of levosimendan lasts longer.<a class="elsevierStyleCrossRef" href="#bib0285">21</a>In recent years, cystatin C has received considerable attention as a potential alternative to serum creatinine for estimating kidney function, and has consistently proved a better risk marker than creatinine, especially in acute scenarios.<a class="elsevierStyleCrossRef" href="#bib0340">32</a> In our study, admission cystatin C, but not creatinine or BUN, was an independent predictor of CRS during hospital stay. Identifying individuals at risk for developing CRS by assessing cystatin C could help the physician provide a more tailored therapeutic strategy, with a view to decreasing CRS incidence and hence improving this population's dire prognosis.Although multivariate analysis showed the use of dobutamine was associated with a five-fold higher risk of in-hospital mortality, these results need to be assessed with caution, since they conflict with those obtained in large clinical trials comparing the impact of levosimendan and dobutamine on mortality.<a class="elsevierStyleCrossRefs" href="#bib0345">33,34</a> However, these differences may be explained by the differences in systolic blood pressure at admission, since median systolic blood pressure in the levosimendan group was over 100 mmHg. The inclusion of patients with low blood pressure in SURVIVE<a class="elsevierStyleCrossRef" href="#bib0350">34</a> and REVIVE-II<a class="elsevierStyleCrossRef" href="#bib0345">33</a> may have partly explained their results, since the beneficial effects of levosimendan in reducing central venous pressure and improving pulmonary congestion may be offset by a drop in blood pressure, which jeopardizes vital organ perfusion.<a class="elsevierStyleCrossRef" href="#bib0355">35</a> Furthermore, a recent analysis of 25 meta-analyses in different clinical settings consistently showed benefits for levosimendan, with lower relative risk for mortality, which supports our results.<a class="elsevierStyleCrossRef" href="#bib0360">36</a>Study limitationsOur study has several limitations. First, this was a single-center study with a relatively small sample size. A larger sample of patients from multiple centers would make the analysis more robust and objective. Second, the observational nature of the study means that the inotrope used and its doses were at the discretion of the attending physician. Furthermore, the lack of randomization created two heterogeneous populations that clearly differed in severity on admission, which precludes firm conclusions regarding the superiority of levosimendan or dobutamine in terms of renoprotective profile. Finally, although the MDRD formula is currently the preferred method for estimating renal function,<a class="elsevierStyleCrossRef" href="#bib0265">17</a> it should be applied when renal function is stable, which is probably not the case for many patients admitted with AHF.ConclusionsAlthough the differences between groups preclude firm conclusions, levosimendan appears to have some renoprotective effect, as it was associated with a lower incidence of CRS and better recovery of renal function at discharge. This outcome, together with recent publications showing the benefit of levosimendan in renal protection, support the potential role of this drug in the prevention and treatment of CRS. Furthermore, identification of patients at increased risk of renal dysfunction by assessing cystatin C may enable selection of patients for levosimendan treatment, minimizing the incidence of CRS and its indisputably negative impact on AHF prognosis.Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this study.Confidentiality of dataThe authors declare that they have followed the protocols of their work center on the publication of patient data.Right to privacy and informed consentThe authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres904280" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec884875" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres904281" "titulo" => "Resumo" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introdução" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusões" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec884876" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Population and study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Data collection" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Patient characteristics" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Comparison of baseline characteristics and therapeutic strategies" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Primary and secondary endpoints" ] 3 => array:2 [ "identificador" => "sec0050" "titulo" => "In-hospital prognosis" ] 4 => array:2 [ "identificador" => "sec0055" "titulo" => "Follow-up" ] ] ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Study limitations" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Conclusions" ] 10 => array:3 [ "identificador" => "sec0075" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0080" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0085" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0090" "titulo" => "Right to privacy and informed consent" ] ] ] 11 => array:2 [ "identificador" => "sec0095" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-02-10" "fechaAceptado" => "2017-03-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec884875" "palabras" => array:4 [ 0 => "Heart failure" 1 => "Cardiorenal syndrome" 2 => "Levosimendan" 3 => "Dobutamine" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec884876" "palabras" => array:4 [ 0 => "Insuficiência cardíaca" 1 => "Síndrome cardiorrenal" 2 => "Levosimendano" 3 => "Dobutamina" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionCardiorenal syndrome (CRS) is common in acute heart failure (AHF), and is associated with dire prognosis. Levosimendan, a positive inotrope that also has diuretic effects, may improve patients’ renal profile. Published results are conflicting. ObjectivesWe aimed to assess the incidence of CRS in AHF patients according to the inotrope used and to determine its predictors in order to identify patients who could benefit from the most renoprotective inotrope. MethodsIn a retrospective study, 108 consecutive patients with AHF who required inotropes were divided into two groups according to the inotrope used (levosimendan vs. dobutamine). The primary endpoint was CRS incidence. Follow-up for mortality and readmission for AHF was conducted. ResultsSeventy-one percent of the study population were treated with levosimendan and the remainder with dobutamine. No differences were found in heart failure etiology or chronic kidney disease. At admission, the dobutamine group had lower blood pressure; there were no differences in estimated glomerular filtration rate or cystatin C levels. The levosimendan group had lower left ventricular ejection fraction. CRS incidence was higher in the dobutamine group, and they more often had incomplete recovery of renal function at discharge. In multivariate analysis, cystatin C levels predicted CRS. The dobutamine group had higher in-hospital mortality, of which CRS and the inotrope used were predictors. ConclusionsLevosimendan appears to have some renoprotective effect, as it was associated with a lower incidence of CRS and better recovery of renal function at discharge. Identification of patients at increased risk of renal dysfunction by assessing cystatin C may enable more tailored therapy, minimizing the incidence of CRS and its negative impact on outcome in AHF." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "IntroduçãoA síndrome cardiorrenal (SCR) é comum na insuficiência cardíaca aguda (ICA), associando-se a um prognóstico sombrio. O levosimendano, aliando um efeito inotrópico e diurético, poderá ter melhor perfil renal. A literatura é controversa. ObjetivosAvaliar em doentes com ICA a incidência de SCR em função do inotrópico utilizado. Determinar preditores de SCR, identificando os doentes que possam beneficiar do inotrópico com melhor perfil renoprotetor. MétodosEstudo retrospetivo, incluindo 108 doentes consecutivos com ICA tratados com inotrópicos. Criados dois grupos consoante o inotrópico utilizado (levosimendano e dobutamina). O endpoint primário foi incidência de SCR. Realizado seguimento relativo a mortalidade e hospitalização por ICA. ResultadosO levosimendano foi usado em 71% dos doentes e a dobutamina nos restantes. Sem diferenças na etiologia da IC ou incidência de doença renal crónica. À admissão, o grupo-dobutamina apresentava menor pressão arterial sistólica; sem diferenças na taxa de filtração glomerular (TFG) ou cistatina C. O grupo-levosimendano apresentava disfunção ventricular esquerda mais grave. A incidência de SCR foi maior no grupo-dobutamina, com recuperação incompleta da TFG à alta hospitalar. Em análise multivariada, a cistatina C foi preditora de SCR. A mortalidade intra-hospitalar foi superior no grupo-dobutamina, sendo a SCR e o inotrópico utilizado preditores desta. ConclusõesO levosimendano parece ter melhor perfil renal, associando-se a menor incidência de SCR, com recuperação da função renal. A cistatina C, ao identificar os doentes em maior risco de disfunção renal, poderá permitir uma terapêutica mais individualizada, reduzindo a incidência de SCR e seu impacto negativo no prognóstico da ICA." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introdução" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusões" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 702 "Ancho" => 2578 "Tamanyo" => 91401 ] ] "descripcion" => array:1 [ "en" => "Changes in renal function parameters during hospitalization. eGFR: estimated glomerular filtration rate." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "AF: atrial fibrillation; CAD: coronary artery disease; CKD: chronic kidney disease; DbG: dobutamine group; HF: heart failure; LvG: levosimendan group." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LvG (n=77) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">DbG (n=31) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age, years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64±14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73±16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">81% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypertension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.55 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CKD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.42 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of CAD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.42 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ischemic etiology of HF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">New-onset HF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AF at admission \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Previous use of beta-blockers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.16 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1520463.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison of patient characteristics at baseline." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ALT: alanine transaminase; AST: aspartate transaminase; BUN: blood urea nitrogen; DbG: dobutamine group; eGFR: estimated glomerular filtration rate; HF: heart failure; LVEF: left ventricular ejection fraction; LvG: levosimendan group." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LvG (n=77) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">DbG (n=31) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systolic blood pressure, mmHg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">119±32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">104±31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">Laboratory data</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemoglobin, g/dl \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.4±2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.5±2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total bilirubin, μmol/l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21±15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15±8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sodium, mmol/l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">138±4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">138±5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.71 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Potassium, mmol/l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.5±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.6±1.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alkaline phosphatase, U/l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">106±47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">162±106 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AST, U/l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">229±640 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">99±160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.46 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALT, U/l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">170±377 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">111±160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">Renal function</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">eGFR, ml/min/1.73 m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61±30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56±28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.42 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cystatin C, mg/l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.4±0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.6±0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine, μmol/l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">130±59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">131±70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.93 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BUN, mmol/l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14±12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.71 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">Echocardiographic data</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVEF, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35±12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diastolic dysfunction, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.38 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1520462.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main clinical, laboratory and echocardiographic data." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "DbG: dobutamine group; IABP: intra-aortic balloon-pump counterpulsation; LvG: levosimendan group; Max.: maximum." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LvG (n=77) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">DbG (n=31) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Max. daily furosemide dose, mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">147±111 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55±126 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IABP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urgent revascularization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.09 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Noradrenaline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vasodilator dopamine dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Renal support therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mechanical ventilation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Invasive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Noninvasive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.29 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1520461.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main differences in therapeutic strategies between the study groups." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:36 [ 0 => array:3 [ "identificador" => "bib0185" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.S. Nieminen" 1 => "D. Brutsaert" 2 => "K. Dickstein" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehl193" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2006" "volumen" => "27" "paginaInicial" => "2725" "paginaFinal" => "2736" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17000631" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0190" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recommendations on pre-hospital and early hospital management of acute heart failure: a consensus paper from the Heart Failure Association of the European Society of Cardiology, the European Society of Emergency Medicine and the Society of Academic Emergency Medicine" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Mebazaa" 1 => "M.B. Yilmaz" 2 => "P. Levy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ejhf.289" "Revista" => array:6 [ "tituloSerie" => "Eur J Heart Fail" "fecha" => "2015" "volumen" => "17" "paginaInicial" => "544" "paginaFinal" => "558" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25999021" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0195" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal effects of levosimendan: a consensus report" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.B. Yilmaz" 1 => "E. Grossini" 2 => "J.C. Silva Cardoso" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10557-013-6485-6" "Revista" => array:6 [ "tituloSerie" => "Cardiovasc Drugs Ther" "fecha" => "2013" "volumen" => "27" "paginaInicial" => "581" "paginaFinal" => "590" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23929366" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0200" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated heart failure: a report From the ADHERE database" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.T. Heywood" 1 => "G.C. Fonarow" 2 => "M.R. 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Original Article

Inotropes and cardiorenal syndrome in acute heart failure – A retrospective comparative analysis

Inotrópicos e síndrome cardiorrenal na insuficiência cardíaca aguda – análise comparativa retrospetiva

Marta Madeiraa,b,

Corresponding author

marta.jesus.madeira@gmail.com

Corresponding author.

, Francisca Caetanoc, Inês Almeidaa, Andreia Fernandesa, Liliana Reisa, Marco Costaa, Lino Gonçalvesa,b

a Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra – Hospital Geral, Coimbra, Portugal

b Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal

c King's College Hospital NHS Foundation Trust, Critical Care Department, London, United Kingdom

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        "titulo" => "Inotr&#243;picos e s&#237;ndrome cardiorrenal na insufici&#234;ncia card&#237;aca aguda &#8211; an&#225;lise comparativa retrospetiva"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Changes in renal function parameters during hospitalization&#46; eGFR&#58; estimated glomerular filtration rate&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Acute heart failure &#40;AHF&#41; remains the single most common admitting diagnosis in industrialized countries&#44; despite significant advances in pharmacologic and device therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">1&#44;2</span></a> Some degree of renal impairment is present in more than a third of patients with AHF&#44; associated with reduction in renal blood flow and&#47;or elevation in central venous pressure&#44; leading to a decrease in estimated glomerular filtration rate &#40;eGFR&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">3&#8211;5</span></a> Conversely&#44; renal impairment itself may predispose to worsening heart failure &#40;HF&#41;&#44; through constant salt and water retention&#44; diuretic resistance and neurohormonal activation&#44; leading to increased cardiac workload&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">6&#44;7</span></a> In a broad spectrum of patients with chronic HF in the CHARM study&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">8</span></a> renal dysfunction was independently associated with increased risk of death&#44; cardiovascular death&#44; and hospitalization due to AHF&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">9</span></a> Furthermore&#44; in advanced chronic HF&#44; renal impairment was a stronger predictor of mortality than either left ventricular ejection fraction &#40;LVEF&#41; or New York Heart Association &#40;NYHA&#41; functional class&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Both dobutamine and levosimendan are inotropic drugs&#44; used specifically to improve cardiac contractility&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">11</span></a> Through activation of ATP-sensitive potassium channels&#44; levosimendan causes both arterial and venous vasodilation &#40;mainly the latter&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">11</span></a> This additional effect of levosimendan over dobutamine may be crucial in AHF&#44; since central venous pressure is an independent predictor of cardiorenal syndrome &#40;CRS&#41; in this setting&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">However&#44; only a few studies comparing the effects of levosimendan with dobutamine on renal function in patients hospitalized with AHF have been published&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">13&#44;14</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We aimed to assess the incidence of CRS according to the inotrope used and to determine its predictors in order to identify patients who could benefit from the most renoprotective inotrope&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The primary endpoint was CRS incidence during hospital stay&#46; The secondary endpoints were recovery of eGFR at discharge&#44; readmission for AHF and mortality during follow-up&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Population and study design</span><p id="par0030" class="elsevierStylePara elsevierViewall">We retrospectively studied 108 consecutive patients admitted between May 2009 and March 2014 to a single cardiac intensive care unit for AHF with symptoms or signs of severe congestion or low cardiac output requiring inotropes&#46; The diagnosis of AHF was established according to the current European Society of Cardiology guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">15</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Patients with end-stage renal disease on a regular program of renal replacement therapy were excluded&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The sample was divided into two groups according to the inotrope used &#40;levosimendan or dobutamine&#41;&#44; prescribed at the discretion of the admitting physician&#46; In the levosimendan group no initial bolus was given and perfusion was started at 0&#46;1 &#956;g&#47;kg&#47;min and titrated up to 0&#46;2 &#956;g&#47;kg&#47;min if tolerated&#46; In the dobutamine group perfusion was started at 5&#46;0 &#956;g&#47;kg&#47;min and titrated on a clinical basis&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">CRS was defined as an increase of &#8805;26&#46;5 &#956;mol&#47;l in serum creatinine relative to the admission value&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">16</span></a> The Modification of Diet in Renal Disease &#40;MDRD&#41; equation was used to calculate eGFR&#44; according to the recommendations of the KDIGO Clinical Practice Guideline for Acute Kidney Injury&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">17</span></a> Changes in renal function were assessed by determining maximum and discharge creatinine and blood urea nitrogen &#40;BUN&#41; and minimum eGFR&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The study is in accordance with the principles outlined in the Declaration of Helsinki&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Data collection</span><p id="par0055" class="elsevierStylePara elsevierViewall">Baseline data were collected from patients&#8217; medical records and included previous medical history &#40;time course and etiology of HF&#44; ischemic heart disease&#44; hypertension&#44; diabetes and chronic renal failure and current therapy&#41;&#44; physical examination at admission &#40;heart rate and blood pressure&#41;&#44; electrocardiogram and blood test analysis &#40;creatinine&#44; BUN&#44; ionogram&#44; N-terminal pro-B-type natriuretic peptide &#91;NT-pro-BNP&#93;&#44; hemoglobin&#44; total bilirubin&#44; alkaline phosphatase&#44; aspartate transaminase &#91;AST&#93;&#44; alanine transaminase &#91;ALT&#93; and cystatin C&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">All patients underwent transthoracic echocardiography with assessment of both systolic &#40;LVEF by the modified Simpson&#39;s rule&#41; and diastolic function&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Therapies analyzed were maximum daily dose of furosemide and type of administration &#40;bolus vs&#46; perfusion&#41;&#44; use of vasodilator doses of dopamine and noradrenaline&#44; renal support therapy and noninvasive or invasive mechanical ventilation&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In-hospital mortality and length of hospital stay were analyzed&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Readmission for AHF and mortality during follow-up were also obtained from clinical records from outpatient clinic&#44; hospital ward and emergency department admissions and through phone calls for patients not followed at our hospital&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">The statistical analysis was performed with SPSS version 21&#46;0 &#40;IBM SPSS Inc&#46;&#44; Chicago&#44; IL&#44; USA&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Data were summarized using means&#44; standard errors&#44; numbers and percentages&#44; as appropriate&#46; The chi-square test was used for dichotomous variables and the independent-samples t test for continuous variables with normal distribution&#46; Multivariate analysis was used to determine predictors of CRS and in-hospital mortality&#46; Statistical significance was defined as p&#60;0&#46;05&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Patient characteristics</span><p id="par0090" class="elsevierStylePara elsevierViewall">One hundred and eight consecutive patients admitted to our cardiac intensive care unit with AHF were studied&#46; Mean age was 66&#177;15 years and 74&#37; were male&#46; According to the decision of the admitting physician&#44; 77 patients &#40;71&#37;&#41; were treated with levosimendan and the remaining 31 &#40;29&#37;&#41; with dobutamine&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Comparison of baseline characteristics and therapeutic strategies</span><p id="par0095" class="elsevierStylePara elsevierViewall">Patients in the levosimendan group were younger and more frequently male&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">No differences were found between the groups in HF etiology &#40;ischemic vs&#46; non-ischemic&#41; or previous history of coronary artery disease&#44; hypertension&#44; diabetes or chronic kidney disease&#46; In both groups&#44; the incidence of new-onset HF was similar&#46; The most frequent precipitating factor &#40;acute coronary syndrome&#58; 35&#37; vs&#46; 55&#37;&#44; p&#61;0&#46;06&#41; was similar in both groups&#44; as were atrial fibrillation incidence at admission and previous use of beta-blockers&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> presents the details of the above data&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> summarizes the main clinical&#44; laboratory and echocardiographic data at admission&#46; Systolic blood pressure and hemoglobin were lower in the dobutamine group and total bilirubin was higher in the levosimendan group&#44; but there were no differences in sodium&#44; potassium&#44; alkaline phosphatase&#44; AST or ALT&#46; LVEF was lower in the levosimendan group&#44; with no differences between groups regarding prevalence of diastolic dysfunction&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the main differences in treatment between the groups&#46; There were no differences in maximum daily dose of furosemide or its form of administration &#40;bolus vs&#46; infusion&#41;&#46; The use of intra-aortic balloon-pump counterpulsation and urgent revascularization was similar between groups&#46; Noradrenaline and dopamine in vasodilator doses were more frequent in the dobutamine group&#44; as was the need for renal support therapy and mechanical ventilation&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Primary and secondary endpoints</span><p id="par0115" class="elsevierStylePara elsevierViewall">The dobutamine group had a higher incidence of the primary endpoint of CRS &#40;49&#37; vs&#46; 77&#37;&#44; p&#60;0&#46;01&#41; and lower minimum eGFR &#40;44&#177;22 vs&#46; 31&#177;18 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#44; p&#60;0&#46;01&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Furthermore&#44; the percentage of decrease in eGFR during hospital stay was higher in the dobutamine group than in the levosimendan group &#40;24&#177;21&#37; vs&#46; 38&#177;28&#37;&#44; p&#61;0&#46;02&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">At discharge&#44; patients who received dobutamine presented a trend towards partial recovery in renal function &#40;eGFR 56&#177;28 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> at admission vs&#46; 45&#177;25 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> at discharge&#44; p&#61;0&#46;06&#41;&#44; unlike patients treated with levosimendan &#40;eGFR 61&#177;30 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> at admission vs&#46; 60&#177;27 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> at discharge&#44; p&#61;0&#46;67&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Changes in renal function parameters are represented in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">Using logistic regression analysis&#44; which included all variables that differed between the groups&#44; cystatin C &#40;odds ratio &#91;OR&#93; 8&#46;6&#44; 95&#37; confidence interval &#91;CI&#93; 1&#46;8-40&#46;7&#44; p&#61;0&#46;007&#41; was identified as the only predictor for CRS development during hospital stay &#40;p&#61;0&#46;73 for the Hosmer-Lemeshow test&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">In-hospital prognosis</span><p id="par0140" class="elsevierStylePara elsevierViewall">Length of stay was similar in both groups &#40;10&#177;8 vs&#46; 12&#177;9 days&#44; p&#61;0&#46;29&#41;&#46; In-hospital mortality &#40;19&#37;&#41; was higher in the dobutamine group &#40;9&#37; vs&#46; 42&#37;&#44; p&#60;0&#46;01&#41;&#46; CRS &#40;OR 13&#44; 95&#37; CI 1&#46;5-114&#46;4&#44; p&#61;0&#46;02&#41; and the inotrope used &#40;OR for dobutamine 5&#44; 95&#37; CI 1&#46;47-19&#46;92&#44; p&#61;0&#46;01&#41; were independent predictors of mortality&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Follow-up</span><p id="par0145" class="elsevierStylePara elsevierViewall">During follow-up &#40;481&#177;365 days&#41;&#44; 44 patients were readmitted due to AHF and 39 died&#46; There were no differences between the groups regarding mortality &#40;41&#37; vs&#46; 56&#37;&#44; p&#61;0&#46;28&#41;&#44; readmission due to AHF &#40;47&#37; vs&#46; 61&#37;&#44; p&#61;0&#46;29&#41;&#44; or the composite endpoint of death and readmission due to AHF &#40;64&#37; vs&#46; 67&#37;&#44; p&#61;0&#46;85&#41;&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0150" class="elsevierStylePara elsevierViewall">Renal dysfunction is one of the most important and prevalent comorbidities of HF and has emerged as a critical risk factor for prolonged hospitalization and rehospitalization and short- and long-term mortality in patients with AHF&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">18</span></a> The prevalence of CRS in our study was very high in both groups &#40;49&#37; and 77&#37;&#41; &#40;although similar to that reported in a sub-analysis of the ADHERE database<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">4</span></a>&#41;&#44; and was an independent predictor of mortality&#44; associated with a risk of death thirteen times higher than in those who did not develop CRS&#46; The high prevalence of acute kidney injury might be explained by the characteristics of our study population&#44; since we only included patients who required treatment with inotropes&#44; which is a surrogate marker of low cardiac output&#46; Factors such as age &#40;mainly elderly&#41; and high incidences of hypertension&#44; diabetes and coronary artery disease&#44; all of them recognized contributors to renal dysfunction&#44; may also have had an impact&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">4</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Unfortunately&#44; the clinical management of CRS is largely empirical and many drugs traditionally used to treat HF &#40;diuretics&#44; angiotensin-converting enzyme inhibitors&#44; angiotensin receptor blockers&#44; and aldosterone antagonists&#41; may result in renal dysfunction due to their serious side effects&#44; especially following inappropriate or excessive use&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">19&#44;20</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Levosimendan is a positive inotropic drug with vasodilatory properties that has been assessed in several clinical studies in patients with AHF&#44; which demonstrated improvements in renal hemodynamics and laboratory markers of renal function&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">13&#44;14&#44;21&#8211;24</span></a> However&#44; there are few studies comparing the renoprotective profile of levosimendan with that of dobutamine in patients with AHF&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">13&#44;14</span></a> The randomized controlled LIDO trial<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">21</span></a> reported a significant reduction of 9&#37; in creatinine level in patients with almost normal renal function when treated with levosimendan as opposed to dobutamine&#46; In patients with moderate renal impairment&#44; levosimendan was found to have a more robust effect on eGFR&#44; with an increase of 45&#37; at 72 hours&#44; compared with dobutamine infusion&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">21</span></a> Similarly&#44; the nonrandomized PORTLAND study<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">22</span></a> assessed the efficacy and safety of levosimendan in the treatment of AHF in everyday clinical practice&#46; There was rapid improvement in diuresis in previously oliguric patients after beginning levosimendan&#44; along with a reduction in serum creatinine levels that persisted at five days&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">22</span></a> Yilmaz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">13</span></a> investigated 88 consecutive patients with AHF &#40;NYHA class III-IV&#41; who required inotropic therapy&#46; Patients were randomized to receive either levosimendan or dobutamine&#46; While LVEF increased significantly in both treatment groups&#44; the levosimendan group showed significant improvement in eGFR after 24 hours &#40;&#43;15&#46;3&#37;&#41;&#44; while the dobutamine arm showed no difference &#40;-1&#46;33&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">13</span></a> The same group also compared the effects of levosimendan and dobutamine on right ventricular function in 40 consecutive patients with severe chronic biventricular dysfunction and showed that right ventricular function improved more in patients receiving levosimendan&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">14</span></a> Furthermore&#44; in these patients levosimendan improved both 24-hour urine output and creatinine levels&#44; whereas dobutamine produced only a small increase in urine output and no decrease in creatinine levels&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">14</span></a> The beneficial effect of levosimendan on renal function extends beyond AHF&#44; according to two recent meta-analyses&#44; in acute critically ill patients and in the perioperative setting&#44; that showed a reduction in kidney injury&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">25&#44;26</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">In agreement with these findings&#44; our study&#44; which aims to describe a real-world AHF population&#44; showed that&#44; even though eGFR was similar in the two groups at admission&#44; patients treated with levosimendan had a lower incidence of CRS &#40;49&#37; vs&#46; 77&#37;&#41;&#46; Furthermore&#44; renal function recovery at discharge was incomplete in individuals who received dobutamine&#44; unlike in patients selected for levosimendan perfusion&#44; who had a complete recovery&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The mechanisms underlying levosimendan&#39;s renoprotective effect in patients with AHF are not fully understood&#46; Improved hemodynamics&#44; and hence increased kidney perfusion&#44; could play an important role&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">24</span></a> However&#44; in multivariate analysis&#44; levosimendan therapy was shown to predict improved renal function independently of changes in left ventricular performance&#44; suggesting that other factors may be responsible&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">23</span></a> Different possible renoprotective mechanisms of levosimendan have been proposed&#58; an increase in renal blood flow due to hemodynamic improvement&#44;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">27&#44;28</span></a> additional increases in renal perfusion via vasodilation through KATP channel agonism&#44;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">29</span></a> reversal of AT-2-mediated mesangial cell contraction with a consequent increase in glomerular capillary surface area and glomerular filtration rate&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">24</span></a> and possible anti-inflammatory properties&#44; suggesting that it may protect against tubular injury&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">30</span></a> However&#44; systemic venodilation together with pulmonary vasodilation&#44; improving right ventricular performance&#44; is probably the main mechanism distinguishing the effect on renal function of this drug from that of dobutamine&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">13</span></a> Moreover&#44; the formation of an active metabolite of levosimendan may account for the prolonged effect of this drug&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">31</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Nevertheless&#44; in our study some differences between the groups may preclude firm conclusions&#46; Patients in the dobutamine group appeared to present in a more severe condition&#44; as expressed by lower systolic blood pressure&#44; lower hemoglobin levels and older age&#44; and generally requiring more multi-organ support&#46; On the other hand&#44; lower systolic blood pressure may itself have influenced the choice of the inotrope by the admitting physician&#44; since the hypotensive effect of levosimendan lasts longer&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">21</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">In recent years&#44; cystatin C has received considerable attention as a potential alternative to serum creatinine for estimating kidney function&#44; and has consistently proved a better risk marker than creatinine&#44; especially in acute scenarios&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">32</span></a> In our study&#44; admission cystatin C&#44; but not creatinine or BUN&#44; was an independent predictor of CRS during hospital stay&#46; Identifying individuals at risk for developing CRS by assessing cystatin C could help the physician provide a more tailored therapeutic strategy&#44; with a view to decreasing CRS incidence and hence improving this population&#39;s dire prognosis&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Although multivariate analysis showed the use of dobutamine was associated with a five-fold higher risk of in-hospital mortality&#44; these results need to be assessed with caution&#44; since they conflict with those obtained in large clinical trials comparing the impact of levosimendan and dobutamine on mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">33&#44;34</span></a> However&#44; these differences may be explained by the differences in systolic blood pressure at admission&#44; since median systolic blood pressure in the levosimendan group was over 100 mmHg&#46; The inclusion of patients with low blood pressure in SURVIVE<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">34</span></a> and REVIVE-II<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">33</span></a> may have partly explained their results&#44; since the beneficial effects of levosimendan in reducing central venous pressure and improving pulmonary congestion may be offset by a drop in blood pressure&#44; which jeopardizes vital organ perfusion&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">35</span></a> Furthermore&#44; a recent analysis of 25 meta-analyses in different clinical settings consistently showed benefits for levosimendan&#44; with lower relative risk for mortality&#44; which supports our results&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">36</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Study limitations</span><p id="par0190" class="elsevierStylePara elsevierViewall">Our study has several limitations&#46; First&#44; this was a single-center study with a relatively small sample size&#46; A larger sample of patients from multiple centers would make the analysis more robust and objective&#46; Second&#44; the observational nature of the study means that the inotrope used and its doses were at the discretion of the attending physician&#46; Furthermore&#44; the lack of randomization created two heterogeneous populations that clearly differed in severity on admission&#44; which precludes firm conclusions regarding the superiority of levosimendan or dobutamine in terms of renoprotective profile&#46; Finally&#44; although the MDRD formula is currently the preferred method for estimating renal function&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">17</span></a> it should be applied when renal function is stable&#44; which is probably not the case for many patients admitted with AHF&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0195" class="elsevierStylePara elsevierViewall">Although the differences between groups preclude firm conclusions&#44; levosimendan appears to have some renoprotective effect&#44; as it was associated with a lower incidence of CRS and better recovery of renal function at discharge&#46; This outcome&#44; together with recent publications showing the benefit of levosimendan in renal protection&#44; support the potential role of this drug in the prevention and treatment of CRS&#46; Furthermore&#44; identification of patients at increased risk of renal dysfunction by assessing cystatin C may enable selection of patients for levosimendan treatment&#44; minimizing the incidence of CRS and its indisputably negative impact on AHF prognosis&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Ethical disclosures</span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Protection of human and animal subjects</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Confidentiality of data</span><p id="par0205" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Right to privacy and informed consent</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conflicts of interest</span><p id="par0215" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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              "titulo" => "Comparison of baseline characteristics and therapeutic strategies"
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          "clase" => "keyword"
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            0 => "Heart failure"
            1 => "Cardiorenal syndrome"
            2 => "Levosimendan"
            3 => "Dobutamine"
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          "palabras" => array:4 [
            0 => "Insufici&#234;ncia card&#237;aca"
            1 => "S&#237;ndrome cardiorrenal"
            2 => "Levosimendano"
            3 => "Dobutamina"
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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="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cardiorenal syndrome &#40;CRS&#41; is common in acute heart failure &#40;AHF&#41;&#44; and is associated with dire prognosis&#46; Levosimendan&#44; a positive inotrope that also has diuretic effects&#44; may improve patients&#8217; renal profile&#46; Published results are conflicting&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">We aimed to assess the incidence of CRS in AHF patients according to the inotrope used and to determine its predictors in order to identify patients who could benefit from the most renoprotective inotrope&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In a retrospective study&#44; 108 consecutive patients with AHF who required inotropes were divided into two groups according to the inotrope used &#40;levosimendan vs&#46; dobutamine&#41;&#46; The primary endpoint was CRS incidence&#46; Follow-up for mortality and readmission for AHF was conducted&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Seventy-one percent of the study population were treated with levosimendan and the remainder with dobutamine&#46; No differences were found in heart failure etiology or chronic kidney disease&#46; At admission&#44; the dobutamine group had lower blood pressure&#59; there were no differences in estimated glomerular filtration rate or cystatin C levels&#46; The levosimendan group had lower left ventricular ejection fraction&#46; CRS incidence was higher in the dobutamine group&#44; and they more often had incomplete recovery of renal function at discharge&#46; In multivariate analysis&#44; cystatin C levels predicted CRS&#46; The dobutamine group had higher in-hospital mortality&#44; of which CRS and the inotrope used were predictors&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Levosimendan appears to have some renoprotective effect&#44; as it was associated with a lower incidence of CRS and better recovery of renal function at discharge&#46; Identification of patients at increased risk of renal dysfunction by assessing cystatin C may enable more tailored therapy&#44; minimizing the incidence of CRS and its negative impact on outcome in AHF&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introdu&#231;&#227;o</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A s&#237;ndrome cardiorrenal &#40;SCR&#41; &#233; comum na insufici&#234;ncia card&#237;aca aguda &#40;ICA&#41;&#44; associando-se a um progn&#243;stico sombrio&#46; O levosimendano&#44; aliando um efeito inotr&#243;pico e diur&#233;tico&#44; poder&#225; ter melhor perfil renal&#46; A literatura &#233; controversa&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Avaliar em doentes com ICA a incid&#234;ncia de SCR em fun&#231;&#227;o do inotr&#243;pico utilizado&#46; Determinar preditores de SCR&#44; identificando os doentes que possam beneficiar do inotr&#243;pico com melhor perfil renoprotetor&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Estudo retrospetivo&#44; incluindo 108 doentes consecutivos com ICA tratados com inotr&#243;picos&#46; Criados dois grupos consoante o inotr&#243;pico utilizado &#40;levosimendano e dobutamina&#41;&#46; O <span class="elsevierStyleItalic">endpoint</span> prim&#225;rio foi incid&#234;ncia de SCR&#46; Realizado seguimento relativo a mortalidade e hospitaliza&#231;&#227;o por ICA&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">O levosimendano foi usado em 71&#37; dos doentes e a dobutamina nos restantes&#46; Sem diferen&#231;as na etiologia da IC ou incid&#234;ncia de doen&#231;a renal cr&#243;nica&#46; &#192; admiss&#227;o&#44; o grupo-dobutamina apresentava menor press&#227;o arterial sist&#243;lica&#59; sem diferen&#231;as na taxa de filtra&#231;&#227;o glomerular &#40;TFG&#41; ou cistatina C&#46; O grupo-levosimendano apresentava disfun&#231;&#227;o ventricular esquerda mais grave&#46; A incid&#234;ncia de SCR foi maior no grupo-dobutamina&#44; com recupera&#231;&#227;o incompleta da TFG &#224; alta hospitalar&#46; Em an&#225;lise multivariada&#44; a cistatina C foi preditora de SCR&#46; A mortalidade intra-hospitalar foi superior no grupo-dobutamina&#44; sendo a SCR e o inotr&#243;pico utilizado preditores desta&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclus&#245;es</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">O levosimendano parece ter melhor perfil renal&#44; associando-se a menor incid&#234;ncia de SCR&#44; com recupera&#231;&#227;o da fun&#231;&#227;o renal&#46; A cistatina C&#44; ao identificar os doentes em maior risco de disfun&#231;&#227;o renal&#44; poder&#225; permitir uma terap&#234;utica mais individualizada&#44; reduzindo a incid&#234;ncia de SCR e seu impacto negativo no progn&#243;stico da ICA&#46;</p></span>"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">AF&#58; atrial fibrillation&#59; CAD&#58; coronary artery disease&#59; CKD&#58; chronic kidney disease&#59; DbG&#58; dobutamine group&#59; HF&#58; heart failure&#59; LvG&#58; levosimendan group&#46;</p>"
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LvG &#40;n&#61;77&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age&#44; years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">71&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of CAD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ischemic etiology of HF&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">New-onset HF&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AF at admission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparison of patient characteristics at baseline&#46;</p>"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">ALT&#58; alanine transaminase&#59; AST&#58; aspartate transaminase&#59; BUN&#58; blood urea nitrogen&#59; DbG&#58; dobutamine group&#59; eGFR&#58; estimated glomerular filtration rate&#59; HF&#58; heart failure&#59; LVEF&#58; left ventricular ejection fraction&#59; LvG&#58; levosimendan group&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LvG &#40;n&#61;77&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">DbG &#40;n&#61;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Systolic blood pressure&#44; mmHg</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">119&#177;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">104&#177;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Laboratory data</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hemoglobin&#44; g&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;4&#177;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;5&#177;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Total bilirubin&#44; &#956;mol&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&#177;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#177;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sodium&#44; mmol&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">138&#177;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">138&#177;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Potassium&#44; mmol&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;5&#177;0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;6&#177;1&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Alkaline phosphatase&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">106&#177;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">162&#177;106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>AST&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">229&#177;640&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">99&#177;160&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ALT&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">170&#177;377&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">111&#177;160&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Renal function</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>eGFR&#44; ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&#177;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56&#177;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cystatin C&#44; mg&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;4&#177;0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;6&#177;0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Creatinine&#44; &#956;mol&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">130&#177;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">131&#177;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BUN&#44; mmol&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#177;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#177;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Echocardiographic data</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>LVEF&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#177;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#177;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diastolic dysfunction&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">147&#177;111&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#177;126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;76&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Noradrenaline</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Vasodilator dopamine dose</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Renal support therapy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Mechanical ventilation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Invasive&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Noninvasive&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
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Article information

ISSN: 21742049
Original language: English

DOI:10.1016/j.repce.2017.03.007

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Year/Month	Html	Pdf	Total

2024 November	7	4	11
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2024 July	41	31	72
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2024 March	34	18	52
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2022 October	52	25	77
2022 September	41	22	63
2022 August	43	36	79
2022 July	68	37	105
2022 June	41	46	87
2022 May	37	23	60
2022 April	46	25	71
2022 March	29	48	77
2022 February	37	33	70
2022 January	30	27	57
2021 December	20	40	60
2021 November	36	22	58
2021 October	24	37	61
2021 September	32	27	59
2021 August	40	30	70
2021 July	20	19	39
2021 June	57	29	86
2021 May	39	36	75
2021 April	89	49	138
2021 March	46	26	72
2021 February	56	26	82
2021 January	47	11	58
2020 December	69	17	86
2020 November	27	16	43
2020 October	32	16	48
2020 September	52	17	69
2020 August	26	9	35
2020 July	59	10	69
2020 June	42	18	60
2020 May	41	13	54
2020 April	43	17	60
2020 March	42	16	58
2020 February	110	36	146
2020 January	45	7	52
2019 December	45	5	50
2019 November	137	21	158
2019 October	52	4	56
2019 September	35	14	49
2019 August	41	8	49
2019 July	54	10	64
2019 June	28	11	39
2019 May	27	14	41
2019 April	42	15	57
2019 March	43	11	54
2019 February	67	8	75
2019 January	53	8	61
2018 December	53	10	63
2018 November	200	10	210
2018 October	619	17	636
2018 September	132	15	147
2018 August	130	12	142
2018 July	23	6	29
2018 June	32	14	46
2018 May	43	18	61
2018 April	37	17	54
2018 March	43	16	59
2018 February	21	12	33
2018 January	44	11	55
2017 December	52	19	71
2017 November	37	33	70
2017 October	42	38	80
2017 September	9	5	14

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