Levosimendan in patients with cardiogenic shock complicating myocardial infarction: A meta-analysis

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Rodríguez, L.F. Reyes, J. Monclou, B. Suberviola, M. Bodí, G. Sirgo, J. Solé-Violán, J. Guardiola, D. Barahona, E. Díaz, I. Martín-Loeches, M.I. Restrepo" "autores" => array:13 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Rodríguez" ] 1 => array:2 [ "nombre" => "L.F." "apellidos" => "Reyes" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Monclou" ] 3 => array:2 [ "nombre" => "B." "apellidos" => "Suberviola" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Bodí" ] 5 => array:2 [ "nombre" => "G." "apellidos" => "Sirgo" ] 6 => array:2 [ "nombre" => "J." "apellidos" => "Solé-Violán" ] 7 => array:2 [ "nombre" => "J." "apellidos" => "Guardiola" ] 8 => array:2 [ "nombre" => "D." "apellidos" => "Barahona" ] 9 => array:2 [ "nombre" => "E." "apellidos" => "Díaz" ] 10 => array:2 [ "nombre" => "I." "apellidos" => "Martín-Loeches" ] 11 => array:2 [ "nombre" => "M.I." 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Fang, H. Cao, Z. Wang" "autores" => array:3 [ 0 => array:3 [ "nombre" => "M." "apellidos" => "Fang" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 1 => array:3 [ "nombre" => "H." "apellidos" => "Cao" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:4 [ "nombre" => "Z." "apellidos" => "Wang" "email" => array:1 [ 0 => "18533112993@126.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Intensive Care Medicine, 3rd Hospital of HeBei Medical University, Shi Jiazhuang, China" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Levosimendán en pacientes con choque cardiogénico que complique un infarto de miocardio: metaanálisis" ] ] "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" => 1753 "Ancho" => 3167 "Tamanyo" => 435518 ] ] "descripcion" => array:1 [ "en" => "Forest plot for risk of mortality in RCT and nRCT." ] ] ] "textoCompleto" => "IntroductionCardiogenic shock complicates approximately 5% of myocardial infarctions. Consequent marked hypotension, reduced oxygen supply, and inadequate perfusion of various organs can result in multiple organ dysfunction. Despite utilization of an early revascularization strategy and advancing patients’ care, cardiogenic shock remains the leading cause of death in this population with high hospital mortality rate, approaching 50%.<a class="elsevierStyleCrossRefs" href="#bib0175">1,2</a>In cardiogenic shock complicating myocardial infarction early revascularization of the occluded vessel with a restoration of coronary cardiac blood flow preferably by means of PCI is the first line strategy. A supportive approach is to give mechanical support, such as Extracorporeal Membrane Oxygenation (ECMO).<a class="elsevierStyleCrossRef" href="#bib0185">3</a> For inotropic support in patients with cardiogenic shock the drugs of choice is dobutamine. However, mortality of such patients in cardiogenic shock remains high. Further studies are needed to evaluate new therapeutic approaches to decrease mortality and morbidity of these patients.Levosimendan is a relatively novel inotropic agent, which acts on cardiac troponin C, stabilizing the bound Ca2+, prolonging the interaction between actin and myosin, and thus enhances cardiac contractility.<a class="elsevierStyleCrossRef" href="#bib0190">4</a> It is a calcium-sensitizer agent<a class="elsevierStyleCrossRef" href="#bib0195">5</a> with vasodilatory properties,<a class="elsevierStyleCrossRef" href="#bib0200">6</a> exerting beneficial effects particularly in cardiac surgery, a setting where it recently showed a survival benefit when compared with dobutamine.<a class="elsevierStyleCrossRef" href="#bib0205">7</a>More recently, a number of clinical trials have now been completed. Therefore, the principal objective of this study was to critically review the literature to evaluate whether levosimendan compared to standard therapy, in patients with cardiogenic shock complicating myocardial infarction, is associated with improved clinical outcomes, in particular survival, and hemodynamics.Materials and methodsSearch strategyAppropriate studies were independently searched in BioMedCentral, PubMed, EMBASE, Cochrane Central Register of clinical trials, and Chinese database (CNKI, WANGFANG DATA, and CQVIP) by 2 investigators. The full PubMed search strategy is available in the Appendix A. Supplementary data. No language restriction was enforced. The search was finalized on 1st May 2016. We decided to use a basic search strategy in order to make the strategy as sensitive as possible.Abstracts from recent international conferences were searched for additional relevant studies. In addition, we use backward snowballing (i.e. scanning of references of retrieved articles and pertinent reviews). The search strategy aimed to include any controlled study with levosimendan administration in cardiogenic shock complicating myocardial infarction in adult humans.Study selectionTwo authors reviewed all abstracts to identify potentially eligible controlled trials. If it was possible, full text articles were retrieved and reviewed to determine whether they met the eligibility criteria. If the complete paper was not available in the database, the corresponding author was contacted to get further material. Disagreements between reviewers were resolved by consensus.The inclusion criteria was reports of controlled trials, comparing levosimendan to any other therapy for cardiogenic shock in adult human and reported at least one outcome of interest. The primary outcome was mortality, whereas secondary outcomes were length of ICU stay, Sequential Organ Failure Assessment (SOFA) score, cardiac index (CI), cardiac powder index (CPI), ejection fraction (EF), end systolic volume (ESV), mean blood pressure (MBP), pulmonary atrial pressure (PAP), mixed venous oxygen saturation (SvO2), glomerular filtration rate (GFR), and pulmonary artery occlusion pressure (PAOP). The time points of the collection of these variables should follow what reported by authors. There were no restrictions on time or dose of administration. The exclusion criteria were: duplicate publications, pediatric studies, and non-intravenous administration of levosimendan.Data abstraction and study characteristicsTwo investigators abstracted baseline, procedural, and outcome data by using a data-recording table developed for this purpose. Data collected included: patient baseline characteristics, study design, sample size, clinical setting, study definition of cardiogenic shock, details of levosimendan and control regimens, and clinical outcomes.Internal validity and risk of bias assessmentThe internal validity of each randomized controlled trial (RCT) was critically assessed for bias as reported by the Cochrane Collaboration methods.<a class="elsevierStyleCrossRef" href="#bib0210">8</a> Each report was evaluated for risk of bias associated with the random sequence generation method, allocation concealment, blinding of participants and personnel, completeness of outcome data, free of selective reporting, and other bias. The overall risk of bias was presented as low, unclear, or high.The internal validity of each non-randomized controlled trial (nRCT) was critically assessed for bias as reported by the Newcastle–Ottawa Scale Risk assessment for case-control studies.<a class="elsevierStyleCrossRef" href="#bib0215">9</a> Each article was evaluated for risk of bias associated with selection, comparability, and exposure. We rated the risk of bias by applying a rating of star number to determine whether adequate measures were taken to protect against each potential source of bias in each study. The overall risk of bias was presented as star number.Data analysis and synthesisTo analyze the binary outcome, we calculated risk ratio (RR) and 95% confidence interval. Mean difference (MD) and 95% confidence interval were computed for continuous variables. Furthermore, we compute numbers needed to be treated. Heterogeneity was measured using the Cochrane Q test, quantified with I2 statistic (I2>25% was defined as threshold indicating significant heterogeneity), and Tau-square (Tau2). The primary analysis was conducted by means of the Peto fixed effects method when I2<25% and with the random effects model when I2>25%. Publication bias was evaluated by visually inspecting funnel plot of the primary outcome.Statistical significance was set at the 2-tailed 0.05 levels for hypothesis testing. Data analysis was performed using Review Manager (RevMan, version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).ResultsLiterature searchThere were 1137 reports identified by the search, 43 full or abstract articles were retrieved for in depth review (Appendix A. Supplementary data). Finally, 13 studies enrolling 648 participants fulfilled all eligibility criteria. There are 5 RCTs with 254 patients<a class="elsevierStyleCrossRefs" href="#bib0220">10–14</a> and 8 nRCTs with 394 patients.<a class="elsevierStyleCrossRefs" href="#bib0245">15–22</a> The trial characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and in Appendix A. Supplementary data. There were 11 studies in English,<a class="elsevierStyleCrossRefs" href="#bib0220">10–12,15–22</a> two in Chinese.<a class="elsevierStyleCrossRefs" href="#bib0235">13,14</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Study quality and risk of bias are reported in the Appendix A. Supplementary data. Two RCTs<a class="elsevierStyleCrossRefs" href="#bib0220">10,12</a> were rated as high risk of bias, 2 RCTs<a class="elsevierStyleCrossRefs" href="#bib0235">13,14</a> at unclear risk, and 1 RCT<a class="elsevierStyleCrossRef" href="#bib0225">11</a> at low risk of bias, according to Cochrane Collaboration methods. Six nRCTs were rated as medium risk of bias,<a class="elsevierStyleCrossRefs" href="#bib0250">16–20,22</a> 2 nRCTs<a class="elsevierStyleCrossRefs" href="#bib0245">15,21</a> were rated as high risk bias, according to Newcastle–Ottawa Scale.Levosimendan in patients with cardiogenic shock: mortalityThe use of levosimendan in patients with cardiogenic shock was associated with a non significant reduction in mortality at the longest follow-up available (68/187 [36%] in the levosimendan group and 121/270 [53%] in the control group, RR 0.82[0.65,1.01], P for effect=0.07, P for heterogeneity=0.88, I2=0%, Tau2 0.00, numbers needed to treat=11; Appendix A. Supplementary data), with 11 studies included. No publication bias was present (Appendix A. Supplementary data).When including only RCTs, there was no statistically significant reduction in mortality at the longest follow-up available in patients with cardiogenic shock (11/37 [29.7%] in the levosimendan group and 14/39[35.9%] in the control group, RR 0.82 [0.43,1.56], P for effect=0.55, P for heterogeneity=0.21, I2=37%, Tau2 0.00, numbers needed to treat=3 Appendix A. Supplementary data); with 3 studies included.Even when including only nRCTs, there was no statistically significant reduction in mortality at the longest follow-up available in patients with cardiogenic shock (57/150 [38%] in the levosimendan group and 107/231[45.0%] in the control group, RR 0.81 [0.65,1.03], P for effect=0.08, P for heterogeneity=0.96, I2=0%, Tau2 0.00, numbers needed to treat=8, Appendix A. Supplementary data); with 8 studies included (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Levosimendan in patients with cardiogenic shock: SOFATwo studies<a class="elsevierStyleCrossRefs" href="#bib0220">10,17</a> reported SOFA that was not significant difference between levosimendan group and control group (MD −1.87[−3.92, 0.18], P for effect=0.07, P for heterogeneity=0.03, I2=72%, Tau2 1.74; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and Appendix A. Supplementary data).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Levosimendan in patients with cardiogenic shock: cardiac functionFour studies<a class="elsevierStyleCrossRefs" href="#bib0220">10,12,17,21</a> reported Cardiac Index that was significantly higher in the levosimendan group when compared with the control group (MD 0.17[0.06, 0.29], P for effect=0.003, P for heterogeneity=0.38, I2=3%, Tau2 0.00; Appendix A. Supplementary data).Three studies<a class="elsevierStyleCrossRefs" href="#bib0220">10,12,17</a> reported Cardiac Power Index (CI*MAP*0.0022) that was significantly higher in the levosimendan group when compared with the control group (MD 0.08[0.03, 0.13], P for effect=0.003, P for heterogeneity=0.08, I2=60%, Tau2 0.00; Appendix A. Supplementary data).Four studies<a class="elsevierStyleCrossRefs" href="#bib0230">12,14,21,22</a> reported Ejection Fraction that was significantly higher in the levosimendan group, when compared with the control group (MD 1.43[1.03, 1.83], P for effect<0.00001, P for heterogeneity=0.29, I2=20%, Tau2 1.33; Appendix A. Supplementary data).Three studies<a class="elsevierStyleCrossRefs" href="#bib0235">13,21,22</a> reported End-Systolic Volume that was significantly lower in the levosimendan group when compared with the control group (MD −6.18[−9.94, −2.42], P for effect=0.001, P for heterogeneity=0.02, I2=76%, Tau2 8.23; Appendix A. Supplementary data).Levosimendan in patients with cardiogenic shock: hemodynamicsTwo studies<a class="elsevierStyleCrossRefs" href="#bib0220">10,17</a> reported Mean Blood Pressure that was significantly higher in the levosimendan group when compared with the control group (MD 3.49[1.05, 5.94], P for effect=0.005, P for heterogeneity=0.60, I2=0%, Tau2 0.00; Appendix A. Supplementary data).Two studies<a class="elsevierStyleCrossRefs" href="#bib0220">10,22</a> reported Pulmonary Atrial Pressure that was significantly lower in the levosimendan group when compared with the control group (MD −4.00[−7.41, −0.58], P for effect=0.02, P for heterogeneity=0.25, I2=24%, Tau2 1.92; Appendix A. Supplementary data).Two studies<a class="elsevierStyleCrossRefs" href="#bib0220">10,19</a> reported SvO2 that was significantly higher in the levosimendan group when compared with the control group (MD 11.40[7.35, 15.44], P for effect<0.00001, P for heterogeneity=0.71, I2=0%, Tau2 0.00; Appendix A. Supplementary data).Two studies<a class="elsevierStyleCrossRefs" href="#bib0220">10,17</a> reported pulmonary artery occlusion pressure (PAOP) was not significant difference between levosimendan group and control group (MD 1.25[−0.12, 2.62], P for effect=0.07, P for heterogeneity=0.88, I2=0%, Tau2 0.00; Appendix A. Supplementary data).DiscussionWe performed a systematic review and meta-analysis of controlled trials and nRCTs to evaluate the effect of levosimendan compared with standard therapies or placebo on survival and hemodynamic parameters in patients presenting cardiogenic shock complicating myocardial infarction. It revealed that levosimendan is associated with improved cardiac function and many hemodynamic parameters, but it was not associated with a significant reduction in mortality, even if a non-significant trend was present. Notably, this is an important meta-analysis performed on levosimendan administration in patients with cardiogenic shock complicating myocardial infarction.Cardiogenic shock is very different from the Low Cardiac Output Syndrome (LCOS). In many studies and meta-analyses, levosimendan was proved more effective than standard therapies in the patients with LCOS.<a class="elsevierStyleCrossRefs" href="#bib0285">23–25</a> The most important difference between cardiogenic shock and LCOS is the reduction in cardiac pump performance with hypo-perfusion to vital organs. Maybe the effect of Levosimendan could benefit more the population of LCOS than cardiogenic shock.Levosimendan is a calcium enhancer with calcium-sensitizing activity. C-AMP independent and ATP neutral induce the improvement in calcium sensitivity of cardiac muscle cell.<a class="elsevierStyleCrossRef" href="#bib0295">25</a> In 2003, Delle-Karth and co-worker<a class="elsevierStyleCrossRef" href="#bib0300">26</a> published the successful use of levosimendan in patients with cardiogenic shock for the first time. In our meta-analysis, Levosimendan may eliminate the SOFA scores, enhance the cardiac functions, improve cardiac ejection fraction and cardiac volume of systolic and diastolic stage, and improve the other hemodynamic parameters. The effects could come from the levosimendan mechanism. Levosimendan exhibits calcium-dependent binding to the N-terminal domain of cardiac troponin C (TnC) with a higher affinity at high calcium concentrations and lower affinity at low calcium concentrations.<a class="elsevierStyleCrossRef" href="#bib0295">25</a> The positive inotropic effect is obtained without increasing intracellular calcium concentration or without a significant increase in myocardial oxygen demand, usually seen with other inotropes.<a class="elsevierStyleCrossRefs" href="#bib0305">27,28</a> This implies that less energy is utilized by the cardiomyocytes, because re-internalization of calcium increases ATP expenditure and accounts for 30% of energy consumed by the cardiomyocyte during the contraction-relaxation cycle. A comparison of levosimendan and milrinone<a class="elsevierStyleCrossRef" href="#bib0315">29</a> showed that both intensify cardiac contraction, but milrinone increased oxygen consumption, levosimendan did not. In other studies, levosimendan was also shown to be superior to dobutamine in term of myocardial efficiency.<a class="elsevierStyleCrossRefs" href="#bib0320">30,31</a>Again, we found that Levosimendan may improve the hemodynamic parameters. Several clinical observations reveal that levosimendan improve hemodynamics even in patients with cardiogenic shock if it is combined with catecholamines to maintain adequate perfusion pressure.<a class="elsevierStyleCrossRefs" href="#bib0330">32,33</a>Levosimendan was associated with a non-significant improve in survival. This may suggest that use of levosimendan in patients with cardiogenic shock complicating myocardial infarction does not offer a mortality benefit or, more probably, that too few patients have been randomized so far to reach powered conclusions on mortality. On the other hand, we also found that levosimendan can improve the hemodynamic parameters. Maybe the pooled analysis could have been insufficiently powered to detect a clinically relevant reduction in mortality in a general population of patients with cardiogenic shock. Perhaps, further larger high-quality RCTs are warranted to reach conclusions on the topic.This meta-analysis has strengths and limitations. The methodological quality of the studies included in this meta-analysis was not optimal, with only one trial presenting low risk of bias.<a class="elsevierStyleCrossRef" href="#bib0225">11</a> Not all trials reported all hemodynamic parameters, so these estimations are drawn from small numbers of measurements and should therefore be interpreted with caution. Unfortunately, there are only 5 randomized trials analyzing the effect of levosimendan in patients with cardiogenic shock. Ideally, a large randomized controlled trial on the lookout for the eventual beneficial effects of levosimendan in cardiogenic shock setting should be performed.ConclusionIn summary, this systematic review of 13 clinical trials found that there was no evidence of survival benefit when levosimendan was compared to control therapies. On the other hand, levosimendan was associated with an improvement in hemodynamics and cardiac function. Further high quality studies on levosimendan for patients with cardiogenic shock complicating myocardial infarction are needed.Authors’ contributionsStudy design: FM; study conduct: FM, CH; data analysis: FM, CH; data interpretation: FM, CH, WZ; writing and revising paper: FM, CH, WZ. All authors read and approved the final manuscript.FundingThere was no funding source for this study.Conflict of interestsThe authors did not have any conflict of interests." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1088213" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Purpose" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1032004" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1088214" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1032003" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Search strategy" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study selection" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Data abstraction and study characteristics" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Internal validity and risk of bias assessment" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Data analysis and synthesis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Literature search" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Levosimendan in patients with cardiogenic shock: mortality" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Levosimendan in patients with cardiogenic shock: SOFA" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Levosimendan in patients with cardiogenic shock: cardiac function" ] 4 => array:2 [ "identificador" => "sec0065" "titulo" => "Levosimendan in patients with cardiogenic shock: hemodynamics" ] ] ] 7 => array:2 [ "identificador" => "sec0070" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0080" "titulo" => "Authors’ contributions" ] 10 => array:2 [ "identificador" => "sec0085" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflict of interests" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-03-07" "fechaAceptado" => "2017-08-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1032004" "palabras" => array:4 [ 0 => "Levosimendan" 1 => "Mortality" 2 => "Myocardial infarction" 3 => "Cardiogenic shock" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1032003" "palabras" => array:4 [ 0 => "Levosimendán" 1 => "Mortalidad" 2 => "Infarto de miocardio" 3 => "Choque cardiogénico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "PurposeCardiac shock is the leading cause of death in patients with acute myocardial infarction. The objective of this systematic review and meta-analysis was to evaluate whether levosimendan, compared to any type of control, is associated with improved clinical outcomes in patients with cardiogenic shock complicating myocardial infarction. Materials and methodsThe PubMed, EMBASE, Cochrane Central Register, and China National Knowledge Information databases were searched for pertinent studies published up until 1 May 2016. Randomized and non-randomized clinical trials comparing levosimendan to standard therapy or placebo, in adult patients with cardiogenic shock complicating myocardial infarction, and reporting at least one outcome of interest were included. The primary outcome was mortality, whereas secondary outcomes were length of ICU stay, SOFA score, cardiac index (CI), cardiac power index (CPI), ejection fraction (EF), end-systolic volume (ESV), mean blood pressure (MBP), pulmonary arterial pressure (PAP), mixed venous oxygen saturation (SvO2), pulmonary artery occlusion pressure (PAOP) and glomerular filtration rate (GFR). We pooled risk ratio (RR) and 95% confidence interval (CI) using fixed and random effects models. ResultsThirteen studies comprising a total of 648 patients were included in the analysis. There was a nonsignificant reduction in mortality with levosimendan compared to the controls (RR=0.82 [0.65–1.01], P for effect=0.07, I2=0%). In the levosimendan group PAP and ESV were significantly reduced, while CI, CPI, EF, MBP and SvO2 were significantly increased. No differences in SOFA score, ICU days, PAOP or GFR were noted. ConclusionsLevosimendan can improve hemodynamic parameters and cardiac function when compared with a control group, with no evidence of benefit in terms of survival." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Purpose" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoEl choque cardiogénico es la principal causa de muerte en pacientes con infarto agudo de miocardio. El objetivo de este metaanálisis y revisión sistemática fue evaluar si, en comparación con cualquier tipo de control, el levosimendán se asocia a mejores efectos clínicos en pacientes con choque cardiogénico que complique un infarto de miocardio. Materiales y métodosSe realizaron búsquedas en las bases de datos PubMed, EMBASE, Cochrane Central Register y China National Knowledge Information para encontrar estudios pertinentes publicados hasta el 1 de mayo de 2016. Se incluyeron ensayos clínicos aleatorizados y no aleatorizados en los que se comparase el levosimendán con el tratamiento estándar o con un placebo en pacientes adultos con choque cardiogénico que complicase un infarto de miocardio, y que informasen sobre al menos una variable de interés. La variable principal fue la mortalidad, mientras que las variables secundarias fueron la duración del ingreso en la UCI, la puntuación SOFA, el índice cardíaco (IC), el índice de potencia cardíaca (IPC), la fracción de eyección (FE), el volumen sistólico final (VSF), la presión arterial media (PAM), la presión arterial pulmonar (PAP), la saturación venosa mixta de oxígeno (SvO2), la presión de oclusión de la arteria pulmonar (POAP) y la tasa de filtración glomerular (TFG). Agrupamos la razón de riesgos (RR) y el intervalo de confianza (IC) del 95% por medio de modelos de efectos fijos y aleatorios. ResultadosSe incluyeron en el análisis 13 estudios que incluyeron un total de 648pacientes. Se observó una reducción no significativa de la mortalidad con levosimendán en comparación con los controles (RR=0,82 [0,65-1,01], p para efecto=0,07, I2=0%). En el grupo de tratamiento con levosimendán, la PAP y el VSF se vieron reducidos de forma significativa, mientras que el IC, el IPC, la FE, la PAM y la SvO2 aumentaron de forma significativa. No se observaron diferencias en la puntuación SOFA, los días de ingreso en la UCI, la POAP ni la TFG. ConclusionesEl levosimendán puede mejorar los parámetros hemodinámicos y la función cardíaca en comparación con un grupo de control, si bien no existen evidencias de beneficios en términos de supervivencia." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0105" ] ] ] ] "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" => 1753 "Ancho" => 3167 "Tamanyo" => 435518 ] ] "descripcion" => array:1 [ "en" => "Forest plot for risk of mortality in RCT and nRCT." ] ] 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" => "CS, cardiogenic shock; STEMI, ST elevation myocardial infarction; PCI, percutaneous coronary intervention; AMI, acute myocardial infarction; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; Levo, levosimendan." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study \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">Year \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">Population \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">N \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">RCT (Y/N) \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">Levo bolus (μg/kg) \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">Levo infusion (μg/kg/min) \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">Levo duration (h) \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">Control group \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">Duration of follow-up (days) \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">Christoph \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with STEMI and PCI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IABP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In-hospital \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">Fuhrmann \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with AMI \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="left" valign="top">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Enoximone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \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">Samimi-Fard \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with STEMI and PCI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dobutamine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">360 \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">Soos \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with STEMI and PCI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">106 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Controlled therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">200 \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">Omerovic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with STEMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24–48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Levosimendan contraindicated cohort \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \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">Poli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with STEMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dobutamine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In-hospital \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">Caetano \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with AMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Controlled therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In-hospital \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">Husebye \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Subgroup:CS with STEMI \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="left" valign="top">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1 \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="left" valign="top">Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">180 \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">Affronti \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with AMI and ECMO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1–0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24–48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Catecholamine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In-hospital \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">Katsytadze \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with AMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Necessary conservative treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">360 \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">Mancone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with STEMI and PCI and IABP \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="left" valign="top">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.05–0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Controlled therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \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">Luo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with STEMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1–0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dobutamine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In-hospital \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">Li \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CS with AMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">108 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1–0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dobutamine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1859559.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of the studies included in the meta-analysis." ] ] 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:1 [ "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Outcome of interest \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">No. of studies \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">MD (95% CI) \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><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">I2 (%) \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 (Q test) \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">Tau2 \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">SOFA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.87 [−3.92, 0.18] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.74 \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">Cardiac index (Lmin−1m−2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.17 [0.06, 0.29] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \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><td class="td" title="table-entry " align="char" valign="top">0.00 \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">Cardiac power index (Wm−2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 [0.03, 0.13] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 \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><td class="td" title="table-entry " align="char" valign="top">0.00 \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">Ejection fraction (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.43 [1.03, 1.83] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.0001 \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">0.29 \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">End-systolic volume (ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−6.18 [−9.94, −2.42] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76 \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><td class="td" title="table-entry " align="char" valign="top">8.23 \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">Mean 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">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.49 [1.05, 5.94] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 \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">Pulmonary artery pressure (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−4.00 [−7.41, −0.58] \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><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.92 \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">ScvO2 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.40 [7.35, 15.44] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.00001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \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><td class="td" title="table-entry " align="char" valign="top">0.00 \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">ICU days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.16 [−3.14, 2.83] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 \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">GFR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.54 [−7.04, 14.13] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42.31 \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">PAOP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.25 [−0.12, 2.62] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1859558.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Secondary end points." ] ] 3 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 977613 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:33 [ 0 => array:3 [ "identificador" => "bib0175" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Decline in rates of death and heart failure in acute coronary syndromes, 1999–2006" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.A.A. 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Levosimendan in patients with cardiogenic shock complicating myocardial infarction: A meta-analysis

Levosimendán en pacientes con choque cardiogénico que complique un infarto de miocardio: metaanálisis

M. Fanga,b, H. Caoa, Z. Wanga,

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18533112993@126.com

Corresponding author.

a Department of Intensive Care Medicine, 3rd Hospital of HeBei Medical University, Shi Jiazhuang, China

b Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cardiogenic shock complicates approximately 5&#37; of myocardial infarctions&#46; Consequent marked hypotension&#44; reduced oxygen supply&#44; and inadequate perfusion of various organs can result in multiple organ dysfunction&#46; Despite utilization of an early revascularization strategy and advancing patients&#8217; care&#44; cardiogenic shock remains the leading cause of death in this population with high hospital mortality rate&#44; approaching 50&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In cardiogenic shock complicating myocardial infarction early revascularization of the occluded vessel with a restoration of coronary cardiac blood flow preferably by means of PCI is the first line strategy&#46; A supportive approach is to give mechanical support&#44; such as Extracorporeal Membrane Oxygenation &#40;ECMO&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">3</span></a> For inotropic support in patients with cardiogenic shock the drugs of choice is dobutamine&#46; However&#44; mortality of such patients in cardiogenic shock remains high&#46; Further studies are needed to evaluate new therapeutic approaches to decrease mortality and morbidity of these patients&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Levosimendan is a relatively novel inotropic agent&#44; which acts on cardiac troponin C&#44; stabilizing the bound Ca<span class="elsevierStyleSup">2&#43;</span>&#44; prolonging the interaction between actin and myosin&#44; and thus enhances cardiac contractility&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">4</span></a> It is a calcium-sensitizer agent<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a> with vasodilatory properties&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">6</span></a> exerting beneficial effects particularly in cardiac surgery&#44; a setting where it recently showed a survival benefit when compared with dobutamine&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">More recently&#44; a number of clinical trials have now been completed&#46; Therefore&#44; the principal objective of this study was to critically review the literature to evaluate whether levosimendan compared to standard therapy&#44; in patients with cardiogenic shock complicating myocardial infarction&#44; is associated with improved clinical outcomes&#44; in particular survival&#44; and hemodynamics&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Search strategy</span><p id="par0025" class="elsevierStylePara elsevierViewall">Appropriate studies were independently searched in BioMedCentral&#44; PubMed&#44; EMBASE&#44; Cochrane Central Register of clinical trials&#44; and Chinese database &#40;CNKI&#44; WANGFANG DATA&#44; and CQVIP&#41; by 2 investigators&#46; The full PubMed search strategy is available in the Appendix A&#46; Supplementary data&#46; No language restriction was enforced&#46; The search was finalized on 1st May 2016&#46; We decided to use a basic search strategy in order to make the strategy as sensitive as possible&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Abstracts from recent international conferences were searched for additional relevant studies&#46; In addition&#44; we use backward snowballing &#40;i&#46;e&#46; scanning of references of retrieved articles and pertinent reviews&#41;&#46; The search strategy aimed to include any controlled study with levosimendan administration in cardiogenic shock complicating myocardial infarction in adult humans&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study selection</span><p id="par0035" class="elsevierStylePara elsevierViewall">Two authors reviewed all abstracts to identify potentially eligible controlled trials&#46; If it was possible&#44; full text articles were retrieved and reviewed to determine whether they met the eligibility criteria&#46; If the complete paper was not available in the database&#44; the corresponding author was contacted to get further material&#46; Disagreements between reviewers were resolved by consensus&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The inclusion criteria was reports of controlled trials&#44; comparing levosimendan to any other therapy for cardiogenic shock in adult human and reported at least one outcome of interest&#46; The primary outcome was mortality&#44; whereas secondary outcomes were length of ICU stay&#44; Sequential Organ Failure Assessment &#40;SOFA&#41; score&#44; cardiac index &#40;CI&#41;&#44; cardiac powder index &#40;CPI&#41;&#44; ejection fraction &#40;EF&#41;&#44; end systolic volume &#40;ESV&#41;&#44; mean blood pressure &#40;MBP&#41;&#44; pulmonary atrial pressure &#40;PAP&#41;&#44; mixed venous oxygen saturation &#40;SvO<span class="elsevierStyleInf">2</span>&#41;&#44; glomerular filtration rate &#40;GFR&#41;&#44; and pulmonary artery occlusion pressure &#40;PAOP&#41;&#46; The time points of the collection of these variables should follow what reported by authors&#46; There were no restrictions on time or dose of administration&#46; The exclusion criteria were&#58; duplicate publications&#44; pediatric studies&#44; and non-intravenous administration of levosimendan&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Data abstraction and study characteristics</span><p id="par0045" class="elsevierStylePara elsevierViewall">Two investigators abstracted baseline&#44; procedural&#44; and outcome data by using a data-recording table developed for this purpose&#46; Data collected included&#58; patient baseline characteristics&#44; study design&#44; sample size&#44; clinical setting&#44; study definition of cardiogenic shock&#44; details of levosimendan and control regimens&#44; and clinical outcomes&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Internal validity and risk of bias assessment</span><p id="par0050" class="elsevierStylePara elsevierViewall">The internal validity of each randomized controlled trial &#40;RCT&#41; was critically assessed for bias as reported by the Cochrane Collaboration methods&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">8</span></a> Each report was evaluated for risk of bias associated with the random sequence generation method&#44; allocation concealment&#44; blinding of participants and personnel&#44; completeness of outcome data&#44; free of selective reporting&#44; and other bias&#46; The overall risk of bias was presented as low&#44; unclear&#44; or high&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The internal validity of each non-randomized controlled trial &#40;nRCT&#41; was critically assessed for bias as reported by the Newcastle&#8211;Ottawa Scale Risk assessment for case-control studies&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">9</span></a> Each article was evaluated for risk of bias associated with selection&#44; comparability&#44; and exposure&#46; We rated the risk of bias by applying a rating of star number to determine whether adequate measures were taken to protect against each potential source of bias in each study&#46; The overall risk of bias was presented as star number&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Data analysis and synthesis</span><p id="par0060" class="elsevierStylePara elsevierViewall">To analyze the binary outcome&#44; we calculated risk ratio &#40;RR&#41; and 95&#37; confidence interval&#46; Mean difference &#40;MD&#41; and 95&#37; confidence interval were computed for continuous variables&#46; Furthermore&#44; we compute numbers needed to be treated&#46; Heterogeneity was measured using the Cochrane <span class="elsevierStyleItalic">Q</span> test&#44; quantified with <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> statistic &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>25&#37; was defined as threshold indicating significant heterogeneity&#41;&#44; and Tau-square &#40;Tau<span class="elsevierStyleSup">2</span>&#41;&#46; The primary analysis was conducted by means of the Peto fixed effects method when <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>25&#37; and with the random effects model when <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#62;25&#37;&#46; Publication bias was evaluated by visually inspecting funnel plot of the primary outcome&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Statistical significance was set at the 2-tailed 0&#46;05 levels for hypothesis testing&#46; Data analysis was performed using Review Manager &#40;RevMan&#44; version 5&#46;3&#46; Copenhagen&#58; The Nordic Cochrane Centre&#44; The Cochrane Collaboration&#44; 2014&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Literature search</span><p id="par0070" class="elsevierStylePara elsevierViewall">There were 1137 reports identified by the search&#44; 43 full or abstract articles were retrieved for in depth review &#40;Appendix A&#46; Supplementary data&#41;&#46; Finally&#44; 13 studies enrolling 648 participants fulfilled all eligibility criteria&#46; There are 5 RCTs with 254 patients<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#8211;14</span></a> and 8 nRCTs with 394 patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">15&#8211;22</span></a> The trial characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and in Appendix A&#46; Supplementary data&#46; There were 11 studies in English&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#8211;12&#44;15&#8211;22</span></a> two in Chinese&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">13&#44;14</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Study quality and risk of bias are reported in the Appendix A&#46; Supplementary data&#46; Two RCTs<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#44;12</span></a> were rated as high risk of bias&#44; 2 RCTs<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">13&#44;14</span></a> at unclear risk&#44; and 1 RCT<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">11</span></a> at low risk of bias&#44; according to Cochrane Collaboration methods&#46; Six nRCTs were rated as medium risk of bias&#44;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">16&#8211;20&#44;22</span></a> 2 nRCTs<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">15&#44;21</span></a> were rated as high risk bias&#44; according to Newcastle&#8211;Ottawa Scale&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Levosimendan in patients with cardiogenic shock&#58; mortality</span><p id="par0080" class="elsevierStylePara elsevierViewall">The use of levosimendan in patients with cardiogenic shock was associated with a non significant reduction in mortality at the longest follow-up available &#40;68&#47;187 &#91;36&#37;&#93; in the levosimendan group and 121&#47;270 &#91;53&#37;&#93; in the control group&#44; RR 0&#46;82&#91;0&#46;65&#44;1&#46;01&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;07&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;88&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 0&#46;00&#44; numbers needed to treat<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#59; Appendix A&#46; Supplementary data&#41;&#44; with 11 studies included&#46; No publication bias was present &#40;Appendix A&#46; Supplementary data&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">When including only RCTs&#44; there was no statistically significant reduction in mortality at the longest follow-up available in patients with cardiogenic shock &#40;11&#47;37 &#91;29&#46;7&#37;&#93; in the levosimendan group and 14&#47;39&#91;35&#46;9&#37;&#93; in the control group&#44; RR 0&#46;82 &#91;0&#46;43&#44;1&#46;56&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;55&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;21&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 0&#46;00&#44; numbers needed to treat<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3 Appendix A&#46; Supplementary data&#41;&#59; with 3 studies included&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Even when including only nRCTs&#44; there was no statistically significant reduction in mortality at the longest follow-up available in patients with cardiogenic shock &#40;57&#47;150 &#91;38&#37;&#93; in the levosimendan group and 107&#47;231&#91;45&#46;0&#37;&#93; in the control group&#44; RR 0&#46;81 &#91;0&#46;65&#44;1&#46;03&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;08&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;96&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 0&#46;00&#44; numbers needed to treat<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#44; Appendix A&#46; Supplementary data&#41;&#59; with 8 studies included &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Levosimendan in patients with cardiogenic shock&#58; SOFA</span><p id="par0095" class="elsevierStylePara elsevierViewall">Two studies<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#44;17</span></a> reported SOFA that was not significant difference between levosimendan group and control group &#40;MD &#8722;1&#46;87&#91;&#8722;3&#46;92&#44; 0&#46;18&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;07&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>72&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 1&#46;74&#59; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and Appendix A&#46; Supplementary data&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Levosimendan in patients with cardiogenic shock&#58; cardiac function</span><p id="par0100" class="elsevierStylePara elsevierViewall">Four studies<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#44;12&#44;17&#44;21</span></a> reported Cardiac Index that was significantly higher in the levosimendan group when compared with the control group &#40;MD 0&#46;17&#91;0&#46;06&#44; 0&#46;29&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;38&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 0&#46;00&#59; Appendix A&#46; Supplementary data&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Three studies<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#44;12&#44;17</span></a> reported Cardiac Power Index &#40;CI&#42;MAP&#42;0&#46;0022&#41; that was significantly higher in the levosimendan group when compared with the control group &#40;MD 0&#46;08&#91;0&#46;03&#44; 0&#46;13&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;08&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>60&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 0&#46;00&#59; Appendix A&#46; Supplementary data&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Four studies<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">12&#44;14&#44;21&#44;22</span></a> reported Ejection Fraction that was significantly higher in the levosimendan group&#44; when compared with the control group &#40;MD 1&#46;43&#91;1&#46;03&#44; 1&#46;83&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;00001&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;29&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 1&#46;33&#59; Appendix A&#46; Supplementary data&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Three studies<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">13&#44;21&#44;22</span></a> reported End-Systolic Volume that was significantly lower in the levosimendan group when compared with the control group &#40;MD &#8722;6&#46;18&#91;&#8722;9&#46;94&#44; &#8722;2&#46;42&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>76&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 8&#46;23&#59; Appendix A&#46; Supplementary data&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Levosimendan in patients with cardiogenic shock&#58; hemodynamics</span><p id="par0120" class="elsevierStylePara elsevierViewall">Two studies<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#44;17</span></a> reported Mean Blood Pressure that was significantly higher in the levosimendan group when compared with the control group &#40;MD 3&#46;49&#91;1&#46;05&#44; 5&#46;94&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;60&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 0&#46;00&#59; Appendix A&#46; Supplementary data&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Two studies<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#44;22</span></a> reported Pulmonary Atrial Pressure that was significantly lower in the levosimendan group when compared with the control group &#40;MD &#8722;4&#46;00&#91;&#8722;7&#46;41&#44; &#8722;0&#46;58&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;25&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 1&#46;92&#59; Appendix A&#46; Supplementary data&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Two studies<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#44;19</span></a> reported SvO<span class="elsevierStyleInf">2</span> that was significantly higher in the levosimendan group when compared with the control group &#40;MD 11&#46;40&#91;7&#46;35&#44; 15&#46;44&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;00001&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;71&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 0&#46;00&#59; Appendix A&#46; Supplementary data&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Two studies<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#44;17</span></a> reported pulmonary artery occlusion pressure &#40;PAOP&#41; was not significant difference between levosimendan group and control group &#40;MD 1&#46;25&#91;&#8722;0&#46;12&#44; 2&#46;62&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;07&#44; <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;88&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#44; Tau<span class="elsevierStyleSup">2</span> 0&#46;00&#59; Appendix A&#46; Supplementary data&#41;&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0140" class="elsevierStylePara elsevierViewall">We performed a systematic review and meta-analysis of controlled trials and nRCTs to evaluate the effect of levosimendan compared with standard therapies or placebo on survival and hemodynamic parameters in patients presenting cardiogenic shock complicating myocardial infarction&#46; It revealed that levosimendan is associated with improved cardiac function and many hemodynamic parameters&#44; but it was not associated with a significant reduction in mortality&#44; even if a non-significant trend was present&#46; Notably&#44; this is an important meta-analysis performed on levosimendan administration in patients with cardiogenic shock complicating myocardial infarction&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Cardiogenic shock is very different from the Low Cardiac Output Syndrome &#40;LCOS&#41;&#46; In many studies and meta-analyses&#44; levosimendan was proved more effective than standard therapies in the patients with LCOS&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">23&#8211;25</span></a> The most important difference between cardiogenic shock and LCOS is the reduction in cardiac pump performance with hypo-perfusion to vital organs&#46; Maybe the effect of Levosimendan could benefit more the population of LCOS than cardiogenic shock&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Levosimendan is a calcium enhancer with calcium-sensitizing activity&#46; C-AMP independent and ATP neutral induce the improvement in calcium sensitivity of cardiac muscle cell&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">25</span></a> In 2003&#44; Delle-Karth and co-worker<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> published the successful use of levosimendan in patients with cardiogenic shock for the first time&#46; In our meta-analysis&#44; Levosimendan may eliminate the SOFA scores&#44; enhance the cardiac functions&#44; improve cardiac ejection fraction and cardiac volume of systolic and diastolic stage&#44; and improve the other hemodynamic parameters&#46; The effects could come from the levosimendan mechanism&#46; Levosimendan exhibits calcium-dependent binding to the N-terminal domain of cardiac troponin C &#40;TnC&#41; with a higher affinity at high calcium concentrations and lower affinity at low calcium concentrations&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">25</span></a> The positive inotropic effect is obtained without increasing intracellular calcium concentration or without a significant increase in myocardial oxygen demand&#44; usually seen with other inotropes&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">27&#44;28</span></a> This implies that less energy is utilized by the cardiomyocytes&#44; because re-internalization of calcium increases ATP expenditure and accounts for 30&#37; of energy consumed by the cardiomyocyte during the contraction-relaxation cycle&#46; A comparison of levosimendan and milrinone<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">29</span></a> showed that both intensify cardiac contraction&#44; but milrinone increased oxygen consumption&#44; levosimendan did not&#46; In other studies&#44; levosimendan was also shown to be superior to dobutamine in term of myocardial efficiency&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">30&#44;31</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Again&#44; we found that Levosimendan may improve the hemodynamic parameters&#46; Several clinical observations reveal that levosimendan improve hemodynamics even in patients with cardiogenic shock if it is combined with catecholamines to maintain adequate perfusion pressure&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">32&#44;33</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Levosimendan was associated with a non-significant improve in survival&#46; This may suggest that use of levosimendan in patients with cardiogenic shock complicating myocardial infarction does not offer a mortality benefit or&#44; more probably&#44; that too few patients have been randomized so far to reach powered conclusions on mortality&#46; On the other hand&#44; we also found that levosimendan can improve the hemodynamic parameters&#46; Maybe the pooled analysis could have been insufficiently powered to detect a clinically relevant reduction in mortality in a general population of patients with cardiogenic shock&#46; Perhaps&#44; further larger high-quality RCTs are warranted to reach conclusions on the topic&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">This meta-analysis has strengths and limitations&#46; The methodological quality of the studies included in this meta-analysis was not optimal&#44; with only one trial presenting low risk of bias&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">11</span></a> Not all trials reported all hemodynamic parameters&#44; so these estimations are drawn from small numbers of measurements and should therefore be interpreted with caution&#46; Unfortunately&#44; there are only 5 randomized trials analyzing the effect of levosimendan in patients with cardiogenic shock&#46; Ideally&#44; a large randomized controlled trial on the lookout for the eventual beneficial effects of levosimendan in cardiogenic shock setting should be performed&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conclusion</span><p id="par0170" class="elsevierStylePara elsevierViewall">In summary&#44; this systematic review of 13 clinical trials found that there was no evidence of survival benefit when levosimendan was compared to control therapies&#46; On the other hand&#44; levosimendan was associated with an improvement in hemodynamics and cardiac function&#46; Further high quality studies on levosimendan for patients with cardiogenic shock complicating myocardial infarction are needed&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Authors&#8217; contributions</span><p id="par0175" class="elsevierStylePara elsevierViewall">Study design&#58; FM&#59; study conduct&#58; FM&#44; CH&#59; data analysis&#58; FM&#44; CH&#59; data interpretation&#58; FM&#44; CH&#44; WZ&#59; writing and revising paper&#58; FM&#44; CH&#44; WZ&#46; All authors read and approved the final manuscript&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Funding</span><p id="par0180" class="elsevierStylePara elsevierViewall">There was no funding source for this study&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflict of interests</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors did not have any conflict of interests&#46;</p></span></span>"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Purpose</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cardiac shock is the leading cause of death in patients with acute myocardial infarction&#46; The objective of this systematic review and meta-analysis was to evaluate whether levosimendan&#44; compared to any type of control&#44; is associated with improved clinical outcomes in patients with cardiogenic shock complicating myocardial infarction&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The PubMed&#44; EMBASE&#44; Cochrane Central Register&#44; and China National Knowledge Information databases were searched for pertinent studies published up until 1 May 2016&#46; Randomized and non-randomized clinical trials comparing levosimendan to standard therapy or placebo&#44; in adult patients with cardiogenic shock complicating myocardial infarction&#44; and reporting at least one outcome of interest were included&#46; The primary outcome was mortality&#44; whereas secondary outcomes were length of ICU stay&#44; SOFA score&#44; cardiac index &#40;CI&#41;&#44; cardiac power index &#40;CPI&#41;&#44; ejection fraction &#40;EF&#41;&#44; end-systolic volume &#40;ESV&#41;&#44; mean blood pressure &#40;MBP&#41;&#44; pulmonary arterial pressure &#40;PAP&#41;&#44; mixed venous oxygen saturation &#40;SvO<span class="elsevierStyleInf">2</span>&#41;&#44; pulmonary artery occlusion pressure &#40;PAOP&#41; and glomerular filtration rate &#40;GFR&#41;&#46; We pooled risk ratio &#40;RR&#41; and 95&#37; confidence interval &#40;CI&#41; using fixed and random effects models&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Thirteen studies comprising a total of 648 patients were included in the analysis&#46; There was a nonsignificant reduction in mortality with levosimendan compared to the controls &#40;RR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;82 &#91;0&#46;65&#8211;1&#46;01&#93;&#44; <span class="elsevierStyleItalic">P</span> for effect<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;07&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#41;&#46; In the levosimendan group PAP and ESV were significantly reduced&#44; while CI&#44; CPI&#44; EF&#44; MBP and SvO<span class="elsevierStyleInf">2</span> were significantly increased&#46; No differences in SOFA score&#44; ICU days&#44; PAOP or GFR were noted&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Levosimendan can improve hemodynamic parameters and cardiac function when compared with a control group&#44; with no evidence of benefit in terms of survival&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Purpose"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Materials and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El choque cardiog&#233;nico es la principal causa de muerte en pacientes con infarto agudo de miocardio&#46; El objetivo de este metaan&#225;lisis y revisi&#243;n sistem&#225;tica fue evaluar si&#44; en comparaci&#243;n con cualquier tipo de control&#44; el levosimend&#225;n se asocia a mejores efectos cl&#237;nicos en pacientes con choque cardiog&#233;nico que complique un infarto de miocardio&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materiales y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realizaron b&#250;squedas en las bases de datos PubMed&#44; EMBASE&#44; Cochrane Central Register y China National Knowledge Information para encontrar estudios pertinentes publicados hasta el 1 de mayo de 2016&#46; Se incluyeron ensayos cl&#237;nicos aleatorizados y no aleatorizados en los que se comparase el levosimend&#225;n con el tratamiento est&#225;ndar o con un placebo en pacientes adultos con choque cardiog&#233;nico que complicase un infarto de miocardio&#44; y que informasen sobre al menos una variable de inter&#233;s&#46; La variable principal fue la mortalidad&#44; mientras que las variables secundarias fueron la duraci&#243;n del ingreso en la UCI&#44; la puntuaci&#243;n SOFA&#44; el &#237;ndice card&#237;aco &#40;IC&#41;&#44; el &#237;ndice de potencia card&#237;aca &#40;IPC&#41;&#44; la fracci&#243;n de eyecci&#243;n &#40;FE&#41;&#44; el volumen sist&#243;lico final &#40;VSF&#41;&#44; la presi&#243;n arterial media &#40;PAM&#41;&#44; la presi&#243;n arterial pulmonar &#40;PAP&#41;&#44; la saturaci&#243;n venosa mixta de ox&#237;geno &#40;SvO<span class="elsevierStyleInf">2</span>&#41;&#44; la presi&#243;n de oclusi&#243;n de la arteria pulmonar &#40;POAP&#41; y la tasa de filtraci&#243;n glomerular &#40;TFG&#41;&#46; Agrupamos la raz&#243;n de riesgos &#40;RR&#41; y el intervalo de confianza &#40;IC&#41; del 95&#37; por medio de modelos de efectos fijos y aleatorios&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron en el an&#225;lisis 13 estudios que incluyeron un total de 648<span class="elsevierStyleHsp" style=""></span>pacientes&#46; Se observ&#243; una reducci&#243;n no significativa de la mortalidad con levosimend&#225;n en comparaci&#243;n con los controles &#40;RR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;82 &#91;0&#44;65-1&#44;01&#93;&#44; p para efecto<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;07&#44; I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#41;&#46; En el grupo de tratamiento con levosimend&#225;n&#44; la PAP y el VSF se vieron reducidos de forma significativa&#44; mientras que el IC&#44; el IPC&#44; la FE&#44; la PAM y la SvO<span class="elsevierStyleInf">2</span> aumentaron de forma significativa&#46; No se observaron diferencias en la puntuaci&#243;n SOFA&#44; los d&#237;as de ingreso en la UCI&#44; la POAP ni la TFG&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El levosimend&#225;n puede mejorar los par&#225;metros hemodin&#225;micos y la funci&#243;n card&#237;aca en comparaci&#243;n con un grupo de control&#44; si bien no existen evidencias de beneficios en t&#233;rminos de supervivencia&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Materiales y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0200" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0105"
          ]
        ]
      ]
    ]
    "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" => 1753
            "Ancho" => 3167
            "Tamanyo" => 435518
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Forest plot for risk of mortality in RCT and nRCT&#46;</p>"
        ]
      ]
      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" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">CS&#44; cardiogenic shock&#59; STEMI&#44; ST elevation myocardial infarction&#59; PCI&#44; percutaneous coronary intervention&#59; AMI&#44; acute myocardial infarction&#59; ECMO&#44; extracorporeal membrane oxygenation&#59; IABP&#44; intra-aortic balloon pump&#59; Levo&#44; levosimendan&#46;</p>"
          "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study&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">Year&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">Population&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"><span class="elsevierStyleItalic">N</span>&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">RCT &#40;Y&#47;N&#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">Levo bolus &#40;&#956;g&#47;kg&#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">Levo infusion &#40;&#956;g&#47;kg&#47;min&#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">Levo duration &#40;h&#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">Control group&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">Duration of follow-up &#40;days&#41;&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">Christoph&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with STEMI and PCI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">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;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IABP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In-hospital&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">Fuhrmann&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with AMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">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;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Enoximone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&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">Samimi-Fard&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with STEMI and PCI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&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;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dobutamine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">360&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">Soos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with STEMI and PCI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&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;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Controlled therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">200&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">Omerovic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with STEMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">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;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&#8211;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Levosimendan contraindicated cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&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">Poli&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with STEMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dobutamine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In-hospital&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">Caetano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with AMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Controlled therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In-hospital&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">Husebye&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Subgroup&#58;CS with STEMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&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;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">180&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">Affronti&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with AMI and ECMO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&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;1&#8211;0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&#8211;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Catecholamine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In-hospital&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">Katsytadze&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with AMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Necessary conservative treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">360&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">Mancone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with STEMI and PCI and IABP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&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;05&#8211;0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Controlled therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&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">Luo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with STEMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">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;1&#8211;0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dobutamine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In-hospital&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">Li&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CS with AMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">108&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">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;1&#8211;0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dobutamine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Outcome of interest&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">No&#46; of studies&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">MD &#40;95&#37; CI&#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"><span class="elsevierStyleItalic">P</span>&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"><span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> &#40;&#37;&#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"><span class="elsevierStyleItalic">P</span> &#40;<span class="elsevierStyleItalic">Q</span> test&#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">Tau<span class="elsevierStyleSup">2</span>&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">SOFA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;1&#46;87 &#91;&#8722;3&#46;92&#44; 0&#46;18&#93;&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;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&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;03&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;74&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">Cardiac index &#40;L<span class="elsevierStyleHsp" style=""></span>min<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">&#8722;2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&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;17 &#91;0&#46;06&#44; 0&#46;29&#93;&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;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&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><td class="td" title="table-entry  " align="char" valign="top">0&#46;00&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">Cardiac power index &#40;W<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">&#8722;2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&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 &#91;0&#46;03&#44; 0&#46;13&#93;&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;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&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><td class="td" title="table-entry  " align="char" valign="top">0&#46;00&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">Ejection fraction &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&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;43 &#91;1&#46;03&#44; 1&#46;83&#93;&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;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&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><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">End-systolic volume &#40;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;6&#46;18 &#91;&#8722;9&#46;94&#44; &#8722;2&#46;42&#93;&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;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76&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><td class="td" title="table-entry  " align="char" valign="top">8&#46;23&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">Mean blood pressure &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;49 &#91;1&#46;05&#44; 5&#46;94&#93;&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;005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">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;48&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;00&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">Pulmonary artery pressure &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;4&#46;00 &#91;&#8722;7&#46;41&#44; &#8722;0&#46;58&#93;&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><td class="td" title="table-entry  " align="char" valign="top">24&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;25&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;92&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">ScvO<span class="elsevierStyleInf">2</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;40 &#91;7&#46;35&#44; 15&#46;44&#93;&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;00001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">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;71&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;00&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">ICU days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;16 &#91;&#8722;3&#46;14&#44; 2&#46;83&#93;&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;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">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;59&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;00&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">GFR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 21735727
Original language: English

DOI:10.1016/j.medine.2017.08.015

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Year/Month	Html	Pdf	Total

2024 November	6	11	17
2024 October	60	66	126
2024 September	50	42	92
2024 August	44	50	94
2024 July	48	36	84
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2021 June	32	28	60
2021 May	90	68	158
2021 April	217	90	307
2021 March	148	59	207
2021 February	88	40	128
2021 January	72	37	109
2020 December	96	17	113
2020 November	84	43	127
2020 October	65	50	115
2020 September	53	29	82
2020 August	49	23	72
2020 July	51	35	86
2020 June	48	37	85
2020 May	34	24	58
2020 April	58	16	74
2020 March	52	26	78
2020 February	340	83	423
2020 January	33	39	72
2019 December	30	38	68
2019 November	37	27	64
2019 October	48	33	81
2019 September	40	30	70
2019 August	64	43	107
2019 July	46	47	93
2019 June	142	32	174
2019 May	69	65	134
2019 April	57	31	88
2019 March	31	31	62
2019 February	32	32	64
2019 January	1	6	7
2018 December	1	0	1
2018 October	2	0	2

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