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array:24 [ "pii" => "S1807593222003052" "issn" => "18075932" "doi" => "10.6061/clinics/2020/e1530" "estado" => "S300" "fechaPublicacion" => "2020-01-01" "aid" => "305" "copyright" => "CLINICS" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by/4.0/" "subdocumento" => "fla" "cita" => "Clinics. 2020;75C:" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:19 [ "pii" => "S1807593222003064" "issn" => "18075932" "doi" => "10.6061/clinics/2020/e1539" "estado" => "S300" "fechaPublicacion" => "2020-01-01" "aid" => "306" "copyright" => "CLINICS" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by/4.0/" "subdocumento" => "fla" "cita" => "Clinics. 2020;75C:" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">ORIGINAL ARTICLE</span>" "titulo" => "Choledochal cysts in children: How to Diagnose and Operate on" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 733 "Ancho" => 977 "Tamanyo" => 86532 ] ] "descripcion" => array:1 [ "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Final aspect after resection of the choledochal cyst. Note the small dilated portion of the common hepatic duct and the orifices of both hepatic ducts.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Cristina Aoun Tannuri, Lucas Arjona de Andrade Hara, Guilherme de Freitas Paganoti, Wagner de Castro Andrade, Uenis Tannuri" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Ana Cristina Aoun" "apellidos" => "Tannuri" ] 1 => array:2 [ "nombre" => "Lucas Arjona de Andrade" "apellidos" => "Hara" ] 2 => array:2 [ "nombre" => "Guilherme de Freitas" "apellidos" => "Paganoti" ] 3 => array:2 [ "nombre" => "Wagner de Castro" "apellidos" => "Andrade" ] 4 => array:2 [ "nombre" => "Uenis" "apellidos" => "Tannuri" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222003064?idApp=UINPBA00004N" "url" => "/18075932/000000750000000C/v1_202211290815/S1807593222003064/v1_202211290815/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1807593222003040" "issn" => "18075932" "doi" => "10.6061/clinics/2020/e1529" "estado" => "S300" "fechaPublicacion" => "2020-01-01" "aid" => "304" "copyright" => "CLINICS" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by/4.0/" "subdocumento" => "fla" "cita" => "Clinics. 2020;75C:" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">ORIGINAL ARTICLE</span>" "titulo" => "Clinical and laboratory parameters as predictors of long-term outcome according to the etiology of underlying chronic liver disease in patients who underwent liver transplantation for hepatocellular carcinoma treatment" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1136 "Ancho" => 1277 "Tamanyo" => 67085 ] ] "descripcion" => array:1 [ "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curves of event-free survival in HCC patients according to the etiologic groups of chronic liver disease.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Paulo Henrique Costa Diniz, Serena Dafne do Carmo Silva, Luciana Costa Faria, Paula Vieira Teixeira Vidigal, Teresa Cristina de Abreu Ferrari" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Paulo Henrique Costa" "apellidos" => "Diniz" ] 1 => array:2 [ "nombre" => "Serena Dafne do Carmo" "apellidos" => "Silva" ] 2 => array:2 [ "nombre" => "Luciana Costa" "apellidos" => "Faria" ] 3 => array:2 [ "nombre" => "Paula Vieira Teixeira" "apellidos" => "Vidigal" ] 4 => array:2 [ "nombre" => "Teresa Cristina de Abreu" "apellidos" => "Ferrari" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222003040?idApp=UINPBA00004N" "url" => "/18075932/000000750000000C/v1_202211290815/S1807593222003040/v1_202211290815/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">ORIGINAL ARTICLE</span>" "titulo" => "Intracoronary Sarcoplasmic Reticulum Calcium-ATPase Gene Therapy in Advanced Heart Failure Patients with reduced Ejection Fraction: A Prospective Cohort Study" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Jianfeng Zhang, Guojin Hu, Shengyong Yang" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Jianfeng" "apellidos" => "Zhang" "email" => array:1 [ 0 => "allysonmasonfqj@yahoo.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 1 => array:2 [ "nombre" => "Guojin" "apellidos" => "Hu" ] 2 => array:2 [ "nombre" => "Shengyong" "apellidos" => "Yang" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Cardio-Pulmonary Rehabilitation Inpatient Area, The Second Rehabilitation Hospital of Shanghai, Shanghai 200431, China" "identificador" => "aff1" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 552 "Ancho" => 752 "Tamanyo" => 24139 ] ] "descripcion" => array:1 [ "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Recurrent and terminal events after a follow-up period of 18 months.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Heart failure is a progressive and debilitating disease (<a class="elsevierStyleCrossRef" href="#bib1">1</a>). It is associated with inadequate contractility of the heart (<a class="elsevierStyleCrossRef" href="#bib2">2</a>) due to abnormal calcium cycling (<a class="elsevierStyleCrossRef" href="#bib3">3</a>). Morbidity and mortality in heart failure patients are high (<a class="elsevierStyleCrossRef" href="#bib4">4</a>,<a class="elsevierStyleCrossRef" href="#bib5">5</a>). Drugs for heart failure only slow down the progression of the disease but do not cure the disease (<a class="elsevierStyleCrossRef" href="#bib6">6</a>). Calcium-ATPase deficiency is generally associated with the progression of heart failure (<a class="elsevierStyleCrossRef" href="#bib7">7</a>,<a class="elsevierStyleCrossRef" href="#bib8">8</a>). During diastole, the sarcoplasmic reticulum calcium-ATPase regulates contraction and relaxation of cardiac muscle cells by transporting calcium from the cytosol into the sarcoplasmic reticulum (<a class="elsevierStyleCrossRef" href="#bib9">9</a>). Gene therapy restores the function of the heart as a pump (<a class="elsevierStyleCrossRef" href="#bib2">2</a>). If calcium-ATPase deficiency is corrected, the function of the cardiac muscle cells may be improved in heart failure patients (<a class="elsevierStyleCrossRef" href="#bib7">7</a>).</p><p id="para20" class="elsevierStylePara elsevierViewall">An experimental model (<a class="elsevierStyleCrossRef" href="#bib7">7</a>,<a class="elsevierStyleCrossRef" href="#bib8">8</a>), a phase 2 trial involving a high-dose of sarcoplasmic reticulum calcium-ATPase gene therapy in advanced heart failure patients (<a class="elsevierStyleCrossRef" href="#bib10">10</a>), and a randomized trial (<a class="elsevierStyleCrossRef" href="#bib3">3</a>) involving the use of gene therapy for the treatment of cardiac disease have confirmed the hypothesis that sarcoplasmic reticulum calcium-ATPase gene transfer improves survival and the performance of cardiac muscle cells in heart failure conditions. However, a phase 2b trial involving high-risk ambulatory patients with heart failure (<a class="elsevierStyleCrossRef" href="#bib9">9</a>) revealed that high-dose intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy does not improve cardiac muscle cell performance in heart failure patients. Thus, the favorable effect of targeted intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy in heart failure patients has not been thoroughly investigated.</p><p id="para30" class="elsevierStylePara elsevierViewall">The aim of this study is to test the hypothesis that intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy can improve outcomes and reduce the number of recurrent and terminal events in advanced heart failure patients with reduced ejection fraction.</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">MATERIALS AND METHODS</span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Ethics consideration and consent to participate</span><p id="para40" class="elsevierStylePara elsevierViewall">The designed protocol (SRHS/CL/12/15 dated December 5<span class="elsevierStyleSup">th</span> 2015) of the established study was approved by the review board of Second Rehabilitation Hospital of Shanghai. The study was reported according to the laws of China, strengthening the reporting of observational studies in epidemiology (STROBE) statement, and the 2008 Helsinki Declaration. An informed consent form was signed by all enrolled patients regarding the publication of data on pathology and interventions, including personal data and images (if any), in all formats (hard and/or electronic).</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Inclusion criteria</span><p id="para50" class="elsevierStylePara elsevierViewall">Patients aged 18 to 80 years, who had experienced chronic heart failure as per the 2016 European Society of Cardiology (ESC) Guidelines (<a class="elsevierStyleCrossRef" href="#bib11">11</a>) (confirmed by left ventricular angiography for ejection fraction), and had been undergoing medical treatment for at least one month in the Second Rehabilitation Hospital of Shanghai, Shanghai, China, were considered for the study. Among these patients, only those with the New York Heart Association (NYHA) heart functional classification II to IV (for ischemic or non-ischemic etiology) and a left ventricular ejection fraction 35% or less were included in the analysis. Heart failure patients with undetectable neutralizing antibodies who could not block vector entry of adeno-associated viruses 1 into the target cells were only included in the study.</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Exclusion criteria</span><p id="para60" class="elsevierStylePara elsevierViewall">Patients aged above 80 years, pregnant females, those who had undergone cardiac surgery, and those who had undergone either percutaneous coronary intervention, acute heart failure treatment (positive inotropes, intravenous vasodilators, or diuretics), or valvuloplasty were excluded from the study. Restrictive cardiomyopathic patients, obstructive cardiomyopathic patients, and patients who had amyloidosis (confirmed by blood and urine tests, biopsies of belly fat, and imaging methods), acute myocarditis, infiltrative cardiomyopathy, pericardial disease, thyroid disease, abnormal liver function, anemia, thrombocytopenia, carcinoma, sarcoma, and/or cancer were also excluded from the study.</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">Sample size calculation</span><p id="para70" class="elsevierStylePara elsevierViewall">The sample size was calculated using OpenEpi (Epidemiologic Statistics for Public Health, USA) at a power of 80%. The sample size for both cohorts was calculated as 384.</p></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">Cohorts</span><p id="para80" class="elsevierStylePara elsevierViewall">Patients who received intracoronary 1×10<span class="elsevierStyleSup">13</span> DNase-resistant particles of adeno-associated virus 1 sarcoplasmic reticulum calcium-ATPase (CA) (Luxturna; Sparks Therapeutics, Philadelphia, PA, USA) were assigned to the CA group (n=384) and patients who received oral placebo (Cebocap, Forte Pharmaceutical, Hyderabad, India) were assigned to the PA (placebo group; n=384) (<a class="elsevierStyleCrossRef" href="#bib9">9</a>). Data on the function of the liver, kidney, and other vital organs were reviewed before the administration of calcium-ATPase.</p></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">Recurrent and terminal events during a follow-up period of 18 months</span><p id="para90" class="elsevierStylePara elsevierViewall">The number of hospital admissions due to heart failure and the number of ambulatory treatments for worsening conditions were acquired. Information regarding all causes of death, heart transplantations performed, and the use of a mechanical ventilation system were also collected (<a class="elsevierStyleCrossRef" href="#bib6">6</a>). Additionally, data on the incidences and severity of interventions-emergent adverse events and the number of deaths (cardiovascular-related) were collected (<a class="elsevierStyleCrossRef" href="#bib9">9</a>).</p></span><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">Outcome measures</span><p id="para100" class="elsevierStylePara elsevierViewall">We collected data on blood pressure, changes in the NYHA functional class of the heart, Kansas City Cardiomyopathy Questionnaire (KCCQ; 23-item questionnaire; the score ranged from 0 to 100) score (<a class="elsevierStyleCrossRef" href="#bib12">12</a>), exercise ability (6-min walk test; comparison was made with patients who had no neuromuscular, orthopedic, or rheumatologic abnormality, and were able to walk 300–400 m in 6 min (<a class="elsevierStyleCrossRef" href="#bib6">6</a>)), creatinine level (<a class="elsevierStyleCrossRef" href="#bib10">10</a>), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and at 1, 3, 6, 10, and 18 months after interventions. Endomyocardial biopsy was performed after 18 months of intervention to evaluate the development of new heart failure and/or arrhythmias (<a class="elsevierStyleCrossRef" href="#bib13">13</a>).</p><p id="para110" class="elsevierStylePara elsevierViewall">Outcome measures were collected by physicians and the nursing staff of the institute(s) (all personnel had a minimum of three years of experience). For patients who died during the follow-up period, the last reported data were used for analysis.</p></span><span id="cesec100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle150">Safety</span><p id="para120" class="elsevierStylePara elsevierViewall">All new arrhythmias found during the 18-month follow-up period were recorded.</p></span><span id="cesec110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle160">Statistical analysis</span><p id="para130" class="elsevierStylePara elsevierViewall">For statistical analysis, InStat, 3.1 Window, GraphPad, San Diego, CA, USA was used. For ordinal data, the Chi-square Independence test (<a class="elsevierStyleCrossRef" href="#bib4">4</a>) was used for statistical analysis while the one-way analysis of variance (ANOVA) (<a class="elsevierStyleCrossRef" href="#bib14">14</a>) was used to analyze continuous variables. Logistic regression analysis was performed to evaluate the risk factors for recurrent and terminal events during the 18-month follow-up period. All results were considered significant at a 95% confidence level.</p></span></span><span id="cesec120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle170">RESULTS</span><span id="cesec130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle180">Clinical characteristics</span><p id="para140" class="elsevierStylePara elsevierViewall">Among the enrolled patients, 80% were males and 99% were Han Chinese. Additionally, most of the patients had NYHA heart functional class III. The other clinical characteristics of the patients are presented in <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>. At baseline, both groups had the same demographical and clinical characteristics (<span class="elsevierStyleItalic">p</span>>0.05 for all).</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia></span><span id="cesec140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle190">Recurrent and terminal events</span><p id="para150" class="elsevierStylePara elsevierViewall">After a follow-up period of 18 months, intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy reduced the number of hospital admissions (<span class="elsevierStyleItalic">p</span>=0.001), ambulatory treatments (<span class="elsevierStyleItalic">p</span>=0.0004), and deaths (<span class="elsevierStyleItalic">p</span>=0.024) but was not successful in reducing the number of heart transplantations (<span class="elsevierStyleItalic">p</span>=0.576) and mechanical ventilation incidences (<span class="elsevierStyleItalic">p</span>=0.864, <a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>).</p><elsevierMultimedia ident="fig1"></elsevierMultimedia></span><span id="cesec150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle200">Outcome measures</span><p id="para160" class="elsevierStylePara elsevierViewall">After a follow-up period of 18 months, intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy improved the heart function (<span class="elsevierStyleItalic">p</span>=0.009), left ventricular ejection fraction (<span class="elsevierStyleItalic">p</span><0.0001), KCCQ score (<span class="elsevierStyleItalic">p</span><0.0001), systolic blood pressure (<span class="elsevierStyleItalic">p</span><0.0001), and performance in the 6-min walk test (<span class="elsevierStyleItalic">p</span>=0.047). However, intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy failed to reduce the NT-proBNP (<span class="elsevierStyleItalic">p</span>=0.482) and serum creatinine (<span class="elsevierStyleItalic">p</span>=0.822, <a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>) levels.</p><elsevierMultimedia ident="tbl2"></elsevierMultimedia><p id="para170" class="elsevierStylePara elsevierViewall">Age (<span class="elsevierStyleItalic">p</span>=0.048), NT-proBNP (<span class="elsevierStyleItalic">p</span>=0.046), and placebo treatment (<span class="elsevierStyleItalic">p</span>=0.021) were associated with recurrent and terminal events during the 18-month follow-up period and the effect of the intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy was independent of the confounding variables (<a class="elsevierStyleCrossRef" href="#tbl3">Table 3</a>). Moreover, cumulative recurrent and terminal events/patients were higher in the PA group than in the CA group during the 18-month follow-up period (<span class="elsevierStyleItalic">p</span>=0.015, <a class="elsevierStyleCrossRef" href="#fig2">Figure 2</a>).</p><elsevierMultimedia ident="tbl3"></elsevierMultimedia><elsevierMultimedia ident="fig2"></elsevierMultimedia></span><span id="cesec160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle210">Safety</span><p id="para180" class="elsevierStylePara elsevierViewall">In the CA group, endomyocardial biopsies performed after the 18-month follow-up period, revealed no new arrhythmias or treatment-emergent adverse effects.</p></span></span><span id="cesec170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle220">DISCUSSION</span><p id="para190" class="elsevierStylePara elsevierViewall">In the present study, intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy reduced the number of recurrent and terminal events. In heart failure patients, a decrease in sarcoplasmic reticulum calcium-ATPase activity results in reduced calcium uptake during relaxation (<a class="elsevierStyleCrossRef" href="#bib6">6</a>), which is associated with depressed calcium homeostasis and reduced cardiomyocyte function (<a class="elsevierStyleCrossRef" href="#bib9">9</a>) due to the reduction in the contractile function of the heart (<a class="elsevierStyleCrossRef" href="#bib5">5</a>). Recurrent and terminal events are frequent during the clinical course of patients with cardiac disease (<a class="elsevierStyleCrossRef" href="#bib15">15</a>) due to disturbance of the immune pathway and the short duration of transgene expression (<a class="elsevierStyleCrossRef" href="#bib16">16</a>), which leads to increases in the financial burden of patients (<a class="elsevierStyleCrossRef" href="#bib17">17</a>). The correction of these abnormalities using intracoronary DNase-resistant particles of adeno-associated virus 1 can improve cardiac function and the survival rate (<a class="elsevierStyleCrossRef" href="#bib8">8</a>,<a class="elsevierStyleCrossRef" href="#bib18">18</a>) by improving vascular reactivity and coronary flow (<a class="elsevierStyleCrossRef" href="#bib19">19</a>). Additionally, intracoronary calcium-ATPase transfer decreases the number of ventricular arrhythmias and improves the arrhythmogenic substrate and the factors that trigger it by entering the cardiac cells, where high transduction efficiency is necessary. Moreover, entering of the adeno-associated viruses 1 in cardiac cells tropism provides homogeneous cardiac myocyte transduction (<a class="elsevierStyleCrossRef" href="#bib3">3</a>). The results of the analysis were consistent with the results of previous experimental studies (<a class="elsevierStyleCrossRef" href="#bib16">16</a>,<a class="elsevierStyleCrossRef" href="#bib18">18</a>), pilot studies (<a class="elsevierStyleCrossRef" href="#bib3">3</a>,<a class="elsevierStyleCrossRef" href="#bib9">9</a>), and a phase 2 trial (<a class="elsevierStyleCrossRef" href="#bib10">10</a>), but were not consistent with the results of the phase 2b trial (<a class="elsevierStyleCrossRef" href="#bib9">9</a>). The results of the current study showed that the intracoronary DNase-resistant particles of adeno-associated virus 1 sarcoplasmic reticulum calcium-ATPase may improve the clinical course of heart failure patients with reduced ejection fraction.</p><p id="para200" class="elsevierStylePara elsevierViewall">Intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy improved the NYHA class, performance during the 6-min walk test, left ventricular ejection fraction, KCCQ score, and systolic blood pressure. The improvement in the KCCQ score and 6-min walk test would result in an increase in the ability of patients to perform physical activities, which would result in the improvement of the NYHA class (<a class="elsevierStyleCrossRef" href="#bib20">20</a>). Intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy significantly inhibits left ventricular dilation, which restores systolic functions of the heart (<a class="elsevierStyleCrossRef" href="#bib21">21</a>). The results of the analysis were consistent with the results of the phase 2 trial (<a class="elsevierStyleCrossRef" href="#bib10">10</a>) and experimental studies (<a class="elsevierStyleCrossRef" href="#bib16">16</a>,<a class="elsevierStyleCrossRef" href="#bib22">22</a>). The positive results regarding outcome measures showed that intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy may be beneficial to heart failure patients with reduced ejection fraction.</p><p id="para210" class="elsevierStylePara elsevierViewall">Intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy failed to reduce the NT-proBNP (<span class="elsevierStyleItalic">p</span>=0.482) and creatinine (<span class="elsevierStyleItalic">p</span>=0.822) levels. An NT-proBNP level higher than 1600 pg/mL is responsible for recurrent events (<a class="elsevierStyleCrossRef" href="#bib6">6</a>). The results of the analysis were consistent with the results of another study (<a class="elsevierStyleCrossRef" href="#bib9">9</a>). NT-proBNP released as a result of targets not achieved by intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy (<a class="elsevierStyleCrossRef" href="#bib23">23</a>). In addition, it is well known that the hydrosaline retention state present during heart failure is related not only to the hemodynamic phenomenon due to the heart pumping failure but also as a result of various neurohumoral mechanisms that maintain a reduced glomerular filtration rate, which would remain constant regardless of the improvement in pump function after intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy (<a class="elsevierStyleCrossRef" href="#bib24">24</a>). A negative outcome may slow down, but not deter, further research. These negative results need to be addressed in future randomized trials.</p><p id="para220" class="elsevierStylePara elsevierViewall">Intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy improved the clinical course of the enrolled patients without any treatment-emergent adverse effects. Our results are consistent with those of published studies (<a class="elsevierStyleCrossRef" href="#bib3">3</a>,<a class="elsevierStyleCrossRef" href="#bib9">9</a>,<a class="elsevierStyleCrossRef" href="#bib10">10</a>). Our positive results show that intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy is safe and promising.</p><p id="para230" class="elsevierStylePara elsevierViewall">In this study, gene therapy was performed via intracoronary delivery. The percutaneous, cardiac-perfusion circuit enhances the uptake of the gene by cardiomyocytes (<a class="elsevierStyleCrossRef" href="#bib16">16</a>). However, intracoronary delivery is simple, practical, and also enhances uptake of the gene (<a class="elsevierStyleCrossRef" href="#bib5">5</a>). We recommend intracoronary delivery for gene therapy for optimal effect.</p><p id="para240" class="elsevierStylePara elsevierViewall">In this study, we reported recurrent and terminal events simultaneously. Each recurrent event in patients increases the risk of additional recurrent and terminal events (<a class="elsevierStyleCrossRef" href="#bib25">25</a>). For example, the mortality rate is higher after the fourth hospitalization compared to that after the first hospitalization (<a class="elsevierStyleCrossRef" href="#bib6">6</a>). Thus, to avoid bias, we evaluated recurrent and terminal events simultaneously.</p><p id="para250" class="elsevierStylePara elsevierViewall">One limitation of the study is its prospective nature and the lack of a randomized trial. If a patient died during the follow-up period, the last reported data were used for analysis. This increases the possibility of the occurrence of bias. We did not evaluate the bias between coronary intervention and oral administration.</p></span><span id="cesec180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle230">CONCLUSION</span><p id="para260" class="elsevierStylePara elsevierViewall">Intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy reduces the number of recurrent and terminal events and improves the clinical course of advanced heart failure patients with reduced ejection fraction.</p></span><span id="cesec190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle240">AUTHOR CONTRIBUTIONS</span><p id="para270" class="elsevierStylePara elsevierViewall">All authors read and approved the manuscript for publication. Zhang J contributed to formal analyses, resources, and literature review, and was responsible for the manuscript drafting, review and edition for intellectual content. Hu G was the project administrator and contributed to software development, formal analyses, validation, and literature review. Yang S contributed to resources, data curation, investigation, software development, and literature review. The authors agree to be accountable for all aspects of the work.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:2 [ "identificador" => "xpalclavsec1580064" "titulo" => "KEYWORDS" ] 1 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 2 => array:3 [ "identificador" => "cesec20" "titulo" => "MATERIALS AND METHODS" "secciones" => array:9 [ 0 => array:2 [ "identificador" => "cesec30" "titulo" => "Ethics consideration and consent to participate" ] 1 => array:2 [ "identificador" => "cesec40" "titulo" => "Inclusion criteria" ] 2 => array:2 [ "identificador" => "cesec50" "titulo" => "Exclusion criteria" ] 3 => array:2 [ "identificador" => "cesec60" "titulo" => "Sample size calculation" ] 4 => array:2 [ "identificador" => "cesec70" "titulo" => "Cohorts" ] 5 => array:2 [ "identificador" => "cesec80" "titulo" => "Recurrent and terminal events during a follow-up period of 18 months" ] 6 => array:2 [ "identificador" => "cesec90" "titulo" => "Outcome measures" ] 7 => array:2 [ "identificador" => "cesec100" "titulo" => "Safety" ] 8 => array:2 [ "identificador" => "cesec110" "titulo" => "Statistical analysis" ] ] ] 3 => array:3 [ "identificador" => "cesec120" "titulo" => "RESULTS" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "cesec130" "titulo" => "Clinical characteristics" ] 1 => array:2 [ "identificador" => "cesec140" "titulo" => "Recurrent and terminal events" ] 2 => array:2 [ "identificador" => "cesec150" "titulo" => "Outcome measures" ] 3 => array:2 [ "identificador" => "cesec160" "titulo" => "Safety" ] ] ] 4 => array:2 [ "identificador" => "cesec170" "titulo" => "DISCUSSION" ] 5 => array:2 [ "identificador" => "cesec180" "titulo" => "CONCLUSION" ] 6 => array:2 [ "identificador" => "cesec190" "titulo" => "AUTHOR CONTRIBUTIONS" ] 7 => array:2 [ "identificador" => "xack638082" "titulo" => "ACKNOWLEDGMENTS" ] 8 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-09-07" "fechaAceptado" => "2020-01-07" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "KEYWORDS" "identificador" => "xpalclavsec1580064" "palabras" => array:5 [ 0 => "Cardiac Events" 1 => "Ejection Fraction" 2 => "Heart Failure" 3 => "Intracoronary Delivery" 4 => "Sarcoplasmic Reticulum calcium-ATPase Gene Therapy" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVE:</span><p id="spara60" class="elsevierStyleSimplePara elsevierViewall">Heart failure is a progressive and debilitating disease. Intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy may improve the function of cardiac muscle cells. This study aimed to test the hypothesis that intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy can improve outcomes and reduce the number of recurrent and terminal events in advanced heart failure patients with reduced ejection fraction.</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS:</span><p id="spara70" class="elsevierStyleSimplePara elsevierViewall">A total of 768 heart failure patients with reduced ejection fraction and New York Heart Association classification II to IV were included in this prospective cohort study. Patients either underwent intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy (CA group, n=384) or received oral placebo (PA group; n=384). Data regarding recurrent and terminal event(s), treatment-emergent adverse effects, and outcome measures were collected and analyzed.</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS:</span><p id="spara80" class="elsevierStyleSimplePara elsevierViewall">After a follow-up period of 18 months, intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy reduced the number of hospital admissions (<span class="elsevierStyleItalic">p</span>=0.001), ambulatory treatments (<span class="elsevierStyleItalic">p</span>=0.0004), and deaths (<span class="elsevierStyleItalic">p</span>=0.024). Additionally, intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy improved the left ventricular ejection fraction (<span class="elsevierStyleItalic">p</span><0.0001) and Kansas City Cardiomyopathy Questionnaire score (<span class="elsevierStyleItalic">p</span><0.0001). The number of recurrent and terminal events/patients were higher in the PA group than in the CA group after the follow-up period of 18 months (<span class="elsevierStyleItalic">p</span>=0.015). The effect of the intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy was independent of the confounding variables. No new arrhythmias were reported in the CA group.</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSIONS:</span><p id="spara90" class="elsevierStyleSimplePara elsevierViewall">Intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy reduces the number of recurrent and terminal events and improves the clinical course of advanced heart failure patients with reduced ejection fraction.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "ceabs10" "titulo" => "OBJECTIVE:" ] 1 => array:2 [ "identificador" => "ceabs20" "titulo" => "METHODS:" ] 2 => array:2 [ "identificador" => "ceabs30" "titulo" => "RESULTS:" ] 3 => array:2 [ "identificador" => "ceabs40" "titulo" => "CONCLUSIONS:" ] ] ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "<p class="elsevierStyleNotepara" id="cenpara40">No potential conflict of interest was reported.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 444 "Ancho" => 751 "Tamanyo" => 30517 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Recurrent and terminal events after a follow-up period of 18 months. The chi-square test of independence was performed between the two groups. A <span class="elsevierStyleItalic">p</span>-value <0.05 was considered significant. *A significant fewer values reported than the placebo group.</p>" ] ] 1 => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 552 "Ancho" => 752 "Tamanyo" => 24139 ] ] "descripcion" => array:1 [ "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Recurrent and terminal events after a follow-up period of 18 months.</p>" ] ] 2 => array:7 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="TFN01t01" class="elsevierStyleSimplePara elsevierViewall">NYHA: New York Heart Association.</p><p id="TFN02t01" class="elsevierStyleSimplePara elsevierViewall">KCCQ: Kansas City Cardiomyopathy Questionnaire (range: 0 to 100).</p><p id="TFN03t01" class="elsevierStyleSimplePara elsevierViewall">NT-proBNP: N-terminal pro-B-type natriuretic peptide (NT-proBNP level <1600 pg/mL was considered as normal).</p><p id="TFN04t01" class="elsevierStyleSimplePara elsevierViewall">Ordinal data are shown as frequency (percentage) and continuous variable are shown as mean ± SD.</p><p id="TFN05t01" class="elsevierStyleSimplePara elsevierViewall">The Chi-square Independence test for ordinal data and one-way ANOVA for continuous variables were used for statistical analyses.</p><p id="TFN06t01" class="elsevierStyleSimplePara elsevierViewall">A <span class="elsevierStyleItalic">p</span>-value <0.05 was considered significant.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" colspan="2">Characteristics</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Groups</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " rowspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Comparison between groups</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">CA \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">PA \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Heart failure patients enrolled in the cohort</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">384 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">384 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Treatment</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Intracoronary sarcoplasmic reticulum Calcium-ATPase gene therapy \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Oral placebo \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minimum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.272</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maximum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.12±11.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60.11±13.45 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gender</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">308 (80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">306 (80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.928</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">76 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78 (20) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ethnicity</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Han Chinese \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">380 (99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">379 (98.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.930</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tibetan \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (0.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (0.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mongolian \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (0.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6-min walk test (m)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">315.15±49.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">321.52±61.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.114 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Left ventricular ejection fraction (%)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.12±4.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.92±7.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.058 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NYHA heart functional classification</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.996</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">301 (78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">302 (79) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KCCQ score</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60.12±3.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.68±4.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.09 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NT-proBNP (pg/mL)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1511±102 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1499±99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.099 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cause of heart failure</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Idiopathic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">160 (42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">162 (42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.970</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ischemic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">194 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">191 (50) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hereditary \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypertension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Peripartum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abnormal renal function</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.806 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic obstructive pulmonary disease</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.550 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Creatinine (mg/dL)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.81±0.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.79±0.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.644 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systolic blood pressure (mmHg)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">132±6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">133±8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.051 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Medical treatment</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Special beta-blockers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">155 (41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">165 (43) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.801</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Angiotensin-converting enzyme inhibitors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">101 (26) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99 (26) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Angiotensin II receptor antagonist \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85 (22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 (19) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Aldosterone receptor antagonists \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43 (11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45 (12) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Demographic and clinical characteristics of the enrolled patients.</p>" ] ] 3 => array:7 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="TFN01t02" class="elsevierStyleSimplePara elsevierViewall">BL: At the time of enrollment.</p><p id="TFN02t02" class="elsevierStyleSimplePara elsevierViewall">EL: After a follow-up period of 18 months.</p><p id="TFN03t02" class="elsevierStyleSimplePara elsevierViewall">SA: Statistical analysis between BL and EL.</p><p id="TFN04t02" class="elsevierStyleSimplePara elsevierViewall">Ordinal data are shown as frequency (percentage) and continuous variable are shown as mean ± SD.</p><p id="TFN05t02" class="elsevierStyleSimplePara elsevierViewall">The Chi-square Independence test for ordinal data and one-way ANOVA for continuous variables were used for statistical analyses.</p><p id="TFN06t02" class="elsevierStyleSimplePara elsevierViewall">A <span class="elsevierStyleItalic">p</span>-value <0.05 was considered significant.</p><p id="TFN07t02" class="elsevierStyleSimplePara elsevierViewall">If the patient died during the follow-up period, the last reported data were used for analysis.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" colspan="2">Characteristics</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="6" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Groups</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " rowspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Comparison between groups at EL</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">CA</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">PA</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Treatment</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Intracoronary sarcoplasmic reticulum Calcium-ATPase gene therapy</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Oral placebo</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Level</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">BL \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">EL \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">SA \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">BL \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">EL \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">SA \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Patients enrolled in the cohort</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">384 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">384 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">384 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">384 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NYHA heart functional classification</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">105 (27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.023</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 (19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.891</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.009</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">301 (78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">275 (72) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">302 (79) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">301 (78) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6-min walk test (m)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">315.15±49.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">325.27±51.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.006 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">321.52±61.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">323.47±65.47<a class="elsevierStyleCrossRef" href="#TFN08t02">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.671 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.047 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Left ventricular ejection fraction (%)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.12±4.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29.35±7.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.92±7.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.12±7.65<a class="elsevierStyleCrossRef" href="#TFN08t02">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.708 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KCCQ score</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60.12±3.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65.45±5.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.68±4.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60.01±4.45<a class="elsevierStyleCrossRef" href="#TFN08t02">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.281 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#TFN09t02">§</a>NT-proBNP (pg/mL)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1511±102 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1501±99<a class="elsevierStyleCrossRef" href="#TFN08t02">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.168 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1499±99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1496±98<a class="elsevierStyleCrossRef" href="#TFN08t02">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.673 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.482 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Creatinine (mg/dL)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.81±0.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.79±0.62<a class="elsevierStyleCrossRef" href="#TFN08t02">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.652 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.79±0.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.78±0.6<a class="elsevierStyleCrossRef" href="#TFN08t02">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.817 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.822 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systolic blood pressure (mmHg)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">132±6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">128±5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">133±8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">132±6<a class="elsevierStyleCrossRef" href="#TFN08t02">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.051 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "TFN08t02" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">Insignificant difference with respect to BL.</p>" ] 1 => array:3 [ "identificador" => "TFN09t02" "etiqueta" => "§" "nota" => "<p class="elsevierStyleNotepara" id="cenpara20"><1600 pg/mL was considered normal.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Outcome measures for cardiac function reported after a follow-up period of 18 months.</p>" ] ] 4 => array:7 [ "identificador" => "tbl3" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="TFN01t03" class="elsevierStyleSimplePara elsevierViewall">NYHA: New York Heart Association.</p><p id="TFN02t03" class="elsevierStyleSimplePara elsevierViewall">KCCQ: Kansas City Cardiomyopathy Questionnaire (range from 0 to 100).</p><p id="TFN03t03" class="elsevierStyleSimplePara elsevierViewall">NT-proBNP: N-terminal pro-B-type natriuretic peptide (NT-proBNP level <1600 pg/mL was considered as normal).</p><p id="TFN04t03" class="elsevierStyleSimplePara elsevierViewall">A risk ratio >1 and a <span class="elsevierStyleItalic">p</span>-value <0.05 were considered significant.</p><p id="TFN05t03" class="elsevierStyleSimplePara elsevierViewall">A <span class="elsevierStyleItalic">p</span>-value <0.05 was considered significant.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Heart failure patients included in the analysis</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">768</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Characteristics</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Risk ratio \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">95% CI \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#TFN06t03">*</a>Age (years)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.75-4.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.048 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gender</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.42-1.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.82 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ethnicity</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.53-1.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6-min walk test (m)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.54-1.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.65 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Left ventricular ejection fraction (%)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.67-1.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.68 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NYHA heart functional classification</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.56-1.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.67 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KCCQ score</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.52-1.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.56 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#TFN06t03">*</a>NT-proBNP (pg/mL)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.81-4.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.046 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cause of heart failure</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.82-1.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.56 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abnormal renal function</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.63-1.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic obstructive pulmonary disease</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.68-1.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Creatinine (mg/dL)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.56-1.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Calcium-ATPase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.51-0.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.82 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#TFN06t03">*</a>Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.12-6.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.021 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "TFN06t03" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="cenpara30">Significant factor responsible for recurrent and terminal events after a follow-up period of 18 months.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara50" class="elsevierStyleSimplePara elsevierViewall">The influence of risk factors on recurrent and terminal events after a follow-up period of 18 months.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:25 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "MicroRNA therapy for the failing heart" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ A Martinez-Fernandez \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1161/CIRCGENETICS.114.000687" "Revista" => array:7 [ "tituloSerie" => "Circ Cardiovasc Genet" "fecha" => "2014" "volumen" => "7" "numero" => "3" "paginaInicial" => "393" "paginaFinal" => "394" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24951666" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1161/CIRCGENETICS.114.000687" "WWW" => array:1 [ "link" => "https://doi.org/10.1161/CIRCGENETICS.114.000687" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "AAV-mediated gene therapy for heart failure: enhancing contractility and calcium handling" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ FA Zouein \n \t\t\t\t\t\t\t\t """ 1 => """ GW Booz \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.12703/P5-27" "Revista" => array:5 [ "tituloSerie" => "F1000Prime Rep" "fecha" => "2013" "volumen" => "5" "paginaInicial" => "27" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23967378" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.12703/P5-27" "WWW" => array:1 [ "link" => "https://doi.org/10.12703/P5-27" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term effects of AAV1/SERCA2a gene transfer in patients with severe heart failure: analysis of recurrent cardiovascular events and mortality" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ K Zsebo \n \t\t\t\t\t\t\t\t """ 1 => """ A Yaroshinsky \n \t\t\t\t\t\t\t\t """ 2 => """ JJ Rudy \n \t\t\t\t\t\t\t\t """ 3 => """ K Wagner \n \t\t\t\t\t\t\t\t """ 4 => """ B Greenberg \n \t\t\t\t\t\t\t\t """ 5 => """ M Jessup \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1161/CIRCRESAHA.113.302421" "Revista" => array:7 [ "tituloSerie" => "Circ Res" "fecha" => "2014" "volumen" => "114" "numero" => "1" "paginaInicial" => "101" "paginaFinal" => "108" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24065463" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1161/CIRCRESAHA.113.302421" "WWW" => array:1 [ "link" => "https://doi.org/10.1161/CIRCRESAHA.113.302421" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Contemporary evidence about hospital strategies for reducing 30-day readmissions: a national study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ EH Bradley \n \t\t\t\t\t\t\t\t """ 1 => """ L Curry \n \t\t\t\t\t\t\t\t """ 2 => """ LI Horwitz \n \t\t\t\t\t\t\t\t """ 3 => """ H Sipsma \n \t\t\t\t\t\t\t\t """ 4 => """ JW Thompson \n \t\t\t\t\t\t\t\t """ 5 => """ M Elma \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2012.03.067" "Revista" => array:7 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2012" "volumen" => "60" "numero" => "7" "paginaInicial" => "607" "paginaFinal" => "614" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22818070" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.jacc.2012.03.067" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.jacc.2012.03.067" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "TNF-α down-regulates sarcoplasmic reticulum Ca2? ATPase expression and leads to left ventricular diastolic dysfunction through binding of NF-κB to promoter response element" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ CT Tsai \n \t\t\t\t\t\t\t\t """ 1 => """ CK Wu \n \t\t\t\t\t\t\t\t """ 2 => """ JK Lee \n \t\t\t\t\t\t\t\t """ 3 => """ SN Chang \n \t\t\t\t\t\t\t\t """ 4 => """ YM Kuo \n \t\t\t\t\t\t\t\t """ 5 => """ YC Wang \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1093/cvr/cvv008" "Revista" => array:7 [ "tituloSerie" => "Cardiovasc Res" "fecha" => "2015" "volumen" => "105" "numero" => "3" "paginaInicial" => "318" "paginaFinal" => "329" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25712896" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1093/cvr/cvv008" "WWW" => array:1 [ "link" => "https://doi.org/10.1093/cvr/cvv008" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Design of a phase 2b trial of intracoronary administration of AAV1/SERCA2a in patients with advanced heart failure: the CUPID 2 trial (calcium up-regulation by percutaneous administration of gene therapy in cardiac disease phase 2b)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ B Greenberg \n \t\t\t\t\t\t\t\t """ 1 => """ A Yaroshinsky \n \t\t\t\t\t\t\t\t """ 2 => """ KM Zsebo \n \t\t\t\t\t\t\t\t """ 3 => """ J Butler \n \t\t\t\t\t\t\t\t """ 4 => """ GM Felker \n \t\t\t\t\t\t\t\t """ 5 => """ AA Voors \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.jchf.2013.09.008" "Revista" => array:7 [ "tituloSerie" => "JACC Heart Fail" "fecha" => "2014" "volumen" => "2" "numero" => "1" "paginaInicial" => "84" "paginaFinal" => "92" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24622121" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.jchf.2013.09.008" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.jchf.2013.09.008" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Altered sarcoplasmic reticulum calcium cycling–targets for heart failure therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ C Kho \n \t\t\t\t\t\t\t\t """ 1 => """ A Lee \n \t\t\t\t\t\t\t\t """ 2 => """ RJ Hajjar \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1038/nrcardio.2012.145" "Revista" => array:7 [ "tituloSerie" => "Nat Rev Cardiol" "fecha" => "2012" "volumen" => "9" "numero" => "12" "paginaInicial" => "717" "paginaFinal" => "733" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23090087" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1038/nrcardio.2012.145" "WWW" => array:1 [ "link" => "https://doi.org/10.1038/nrcardio.2012.145" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sarcoplasmic reticulum Ca-ATPase and heart failure 20 years later" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ D Eisner \n \t\t\t\t\t\t\t\t """ 1 => """ J Caldwell \n \t\t\t\t\t\t\t\t """ 2 => """ A Trafford \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1161/CIRCRESAHA.113.302187" "Revista" => array:7 [ "tituloSerie" => "Circ Res" "fecha" => "2013" "volumen" => "113" "numero" => "8" "paginaInicial" => "958" "paginaFinal" => "961" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24071456" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1161/CIRCRESAHA.113.302187" "WWW" => array:1 [ "link" => "https://doi.org/10.1161/CIRCRESAHA.113.302187" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ B Greenberg \n \t\t\t\t\t\t\t\t """ 1 => """ J Butler \n \t\t\t\t\t\t\t\t """ 2 => """ GM Felker \n \t\t\t\t\t\t\t\t """ 3 => """ P Ponikowski \n \t\t\t\t\t\t\t\t """ 4 => """ AA Voors \n \t\t\t\t\t\t\t\t """ 5 => """ AS Desai \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(16)00082-9" "Revista" => array:7 [ "tituloSerie" => "Lancet" "fecha" => "2016" "volumen" => "387" "numero" => "10024" "paginaInicial" => "1178" "paginaFinal" => "1186" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26803443" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/S0140-6736(16)00082-9" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/S0140-6736(16)00082-9" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ M Jessup \n \t\t\t\t\t\t\t\t """ 1 => """ B Greenberg \n \t\t\t\t\t\t\t\t """ 2 => """ D Mancini \n \t\t\t\t\t\t\t\t """ 3 => """ T Cappola \n \t\t\t\t\t\t\t\t """ 4 => """ DF Pauly \n \t\t\t\t\t\t\t\t """ 5 => """ B Jaski \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.111.022889" "Revista" => array:7 [ "tituloSerie" => "Circulation" "fecha" => "2011" "volumen" => "124" "numero" => "3" "paginaInicial" => "304" "paginaFinal" => "313" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21709064" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.111.022889" "WWW" => array:1 [ "link" => "https://doi.org/10.1161/CIRCULATIONAHA.111.022889" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ P Ponikowski \n \t\t\t\t\t\t\t\t """ 1 => """ AA Voors \n \t\t\t\t\t\t\t\t """ 2 => """ SD Anker \n \t\t\t\t\t\t\t\t """ 3 => """ H Bueno \n \t\t\t\t\t\t\t\t """ 4 => """ JGF Cleland \n \t\t\t\t\t\t\t\t """ 5 => """ AJS Coats \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehw128" "Revista" => array:7 [ "tituloSerie" => "Eur Heart J" "fecha" => "2016" "volumen" => "37" "numero" => "27" "paginaInicial" => "2129" "paginaFinal" => "2200" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27206819" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1093/eurheartj/ehw128" "WWW" => array:1 [ "link" => "https://doi.org/10.1093/eurheartj/ehw128" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparable performance of the Kansas City Cardiomyopathy Questionnaire in patients with heart failure with preserved and reduced ejection fraction" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ SM Joseph \n \t\t\t\t\t\t\t\t """ 1 => """ E Novak \n \t\t\t\t\t\t\t\t """ 2 => """ SV Arnold \n \t\t\t\t\t\t\t\t """ 3 => """ PG Jones \n \t\t\t\t\t\t\t\t """ 4 => """ H Khattak \n \t\t\t\t\t\t\t\t """ 5 => """ AE Platts \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1161/CIRCHEARTFAILURE.113.000359" "Revista" => array:7 [ "tituloSerie" => "Circ Heart Fail" "fecha" => "2013" "volumen" => "6" "numero" => "6" "paginaInicial" => "1139" "paginaFinal" => "1146" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24130003" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1161/CIRCHEARTFAILURE.113.000359" "WWW" => array:1 [ "link" => "https://doi.org/10.1161/CIRCHEARTFAILURE.113.000359" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ LT Cooper \n \t\t\t\t\t\t\t\t """ 1 => """ KL Baughman \n \t\t\t\t\t\t\t\t """ 2 => """ AM Feldman \n \t\t\t\t\t\t\t\t """ 3 => """ A Frustaci \n \t\t\t\t\t\t\t\t """ 4 => """ M Jessup \n \t\t\t\t\t\t\t\t """ 5 => """ U Kuhl \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2007.09.008" "Revista" => array:7 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2007" "volumen" => "50" "numero" => "19" "paginaInicial" => "1914" "paginaFinal" => "1931" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17980265" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.jacc.2007.09.008" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.jacc.2007.09.008" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Study of Chloramphenicol for Ophthalmic Formulation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ KC Ashara \n \t\t\t\t\t\t\t\t """ 1 => """ KV Shah \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "IJSRR" "fecha" => "2018" "volumen" => "7" "numero" => "Suppl 1" "paginaInicial" => "173" "paginaFinal" => "181" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hospital strategies to reduce heart failure readmissions: where is the evidence?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ J Butler \n \t\t\t\t\t\t\t\t """ 1 => """ A Kalogeropoulos \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2012.03.066" "Revista" => array:7 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2012" "volumen" => "60" "numero" => "7" "paginaInicial" => "615" "paginaFinal" => "617" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22818073" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.jacc.2012.03.066" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.jacc.2012.03.066" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Augmentation of left ventricular mechanics by recirculation-mediated AAV2/1-SERCA2a gene delivery in experimental heart failure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ JA Mariani \n \t\t\t\t\t\t\t\t """ 1 => """ A Smolic \n \t\t\t\t\t\t\t\t """ 2 => """ A Preovolos \n \t\t\t\t\t\t\t\t """ 3 => """ MJ Byrne \n \t\t\t\t\t\t\t\t """ 4 => """ JM Power \n \t\t\t\t\t\t\t\t """ 5 => """ DM Kaye \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1093/eurjhf/hfq234" "Revista" => array:7 [ "tituloSerie" => "Eur J Heart Fail" "fecha" => "2011" "volumen" => "13" "numero" => "3" "paginaInicial" => "247" "paginaFinal" => "253" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21289077" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1093/eurjhf/hfq234" "WWW" => array:1 [ "link" => "https://doi.org/10.1093/eurjhf/hfq234" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lifetime costs of medical care after heart failure diagnosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ SM Dunlay \n \t\t\t\t\t\t\t\t """ 1 => """ ND Shah \n \t\t\t\t\t\t\t\t """ 2 => """ Q Shi \n \t\t\t\t\t\t\t\t """ 3 => """ B Morlan \n \t\t\t\t\t\t\t\t """ 4 => """ H VanHouten \n \t\t\t\t\t\t\t\t """ 5 => """ KH Long \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1161/CIRCOUTCOMES.110.957225" "Revista" => array:7 [ "tituloSerie" => "Circ Cardiovasc Qual Outcomes" "fecha" => "2011" "volumen" => "4" "numero" => "1" "paginaInicial" => "68" "paginaFinal" => "75" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21139091" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1161/CIRCOUTCOMES.110.957225" "WWW" => array:1 [ "link" => "https://doi.org/10.1161/CIRCOUTCOMES.110.957225" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intramyocardial injection of SERCA2a-expressing lentivirus improves myocardial function in doxorubicin-induced heart failure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ M Mattila \n \t\t\t\t\t\t\t\t """ 1 => """ J Koskenvuo \n \t\t\t\t\t\t\t\t """ 2 => """ M Soderstrom \n \t\t\t\t\t\t\t\t """ 3 => """ K Eerola \n \t\t\t\t\t\t\t\t """ 4 => """ M Savontaus \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1002/jgm.2885" "Revista" => array:7 [ "tituloSerie" => "J Gene Med" "fecha" => "2016" "volumen" => "18" "numero" => "7" "paginaInicial" => "124" "paginaFinal" => "133" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27203155" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1002/jgm.2885" "WWW" => array:1 [ "link" => "https://doi.org/10.1002/jgm.2885" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "SERCA2a gene transfer enhances eNOS expression and activity in endothelial cells" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ L Hadri \n \t\t\t\t\t\t\t\t """ 1 => """ R Bobe \n \t\t\t\t\t\t\t\t """ 2 => """ Y Kawase \n \t\t\t\t\t\t\t\t """ 3 => """ D Ladage \n \t\t\t\t\t\t\t\t """ 4 => """ K Ishikawa \n \t\t\t\t\t\t\t\t """ 5 => """ F Atassi \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1038/mt.2010.77" "Revista" => array:7 [ "tituloSerie" => "Mol Ther" "fecha" => "2010" "volumen" => "18" "numero" => "7" "paginaInicial" => "1284" "paginaFinal" => "1292" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20461063" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1038/mt.2010.77" "WWW" => array:1 [ "link" => "https://doi.org/10.1038/mt.2010.77" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Correlation of the New York Heart Association Classification and the 6-Minute Walk Distance: A Systematic Review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ J Yap \n \t\t\t\t\t\t\t\t """ 1 => """ FY Lim \n \t\t\t\t\t\t\t\t """ 2 => """ F Gao \n \t\t\t\t\t\t\t\t """ 3 => """ LL Teo \n \t\t\t\t\t\t\t\t """ 4 => """ CS Lam \n \t\t\t\t\t\t\t\t """ 5 => """ KK Yeo \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1002/clc.22468" "Revista" => array:7 [ "tituloSerie" => "Clin Cardiol" "fecha" => "2015" "volumen" => "38" "numero" => "10" "paginaInicial" => "621" "paginaFinal" => "628" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26442458" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1002/clc.22468" "WWW" => array:1 [ "link" => "https://doi.org/10.1002/clc.22468" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib21" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "SERCA2a gene therapy for heart failure: ready for primetime?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ M Periasamy \n \t\t\t\t\t\t\t\t """ 1 => """ A Kalyanasundaram \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1038/mt.2008.89" "Revista" => array:7 [ "tituloSerie" => "Mol Ther" "fecha" => "2008" "volumen" => "16" "numero" => "6" "paginaInicial" => "1002" "paginaFinal" => "1004" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18500238" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1038/mt.2008.89" "WWW" => array:1 [ "link" => "https://doi.org/10.1038/mt.2008.89" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib22" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ Y Kawase \n \t\t\t\t\t\t\t\t """ 1 => """ HQ Ly \n \t\t\t\t\t\t\t\t """ 2 => """ F Prunier \n \t\t\t\t\t\t\t\t """ 3 => """ D Lebeche \n \t\t\t\t\t\t\t\t """ 4 => """ Y Shi \n \t\t\t\t\t\t\t\t """ 5 => """ H Jin \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2007.12.014" "Revista" => array:7 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2008" "volumen" => "51" "numero" => "11" "paginaInicial" => "1112" "paginaFinal" => "1119" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18342232" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.jacc.2007.12.014" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.jacc.2007.12.014" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib23" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expression of B-type natriuretic peptide forms in ischemic human hearts" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ R Cortés \n \t\t\t\t\t\t\t\t """ 1 => """ E Roselló-Lletí \n \t\t\t\t\t\t\t\t """ 2 => """ M Rivera \n \t\t\t\t\t\t\t\t """ 3 => """ L Martinez-Dolz \n \t\t\t\t\t\t\t\t """ 4 => """ A Salvador \n \t\t\t\t\t\t\t\t """ 5 => """ R Sirera \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.ijcard.2011.01.014" "Revista" => array:7 [ "tituloSerie" => "Int J Cardiol" "fecha" => "2012" "volumen" => "158" "numero" => "2" "paginaInicial" => "199" "paginaFinal" => "204" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21396728" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.ijcard.2011.01.014" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.ijcard.2011.01.014" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib24" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute myocardial ischemia directly modulates the expression of brain natriuretic peptide at the transcriptional and translational levels via inflammatory cytokines" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ WJ Xia \n \t\t\t\t\t\t\t\t """ 1 => """ YY Huang \n \t\t\t\t\t\t\t\t """ 2 => """ YL Chen \n \t\t\t\t\t\t\t\t """ 3 => """ SL Chen \n \t\t\t\t\t\t\t\t """ 4 => """ JG He \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.ejphar.2011.09.012" "Revista" => array:7 [ "tituloSerie" => "Eur J Pharmacol" "fecha" => "2011" "volumen" => "670" "numero" => "1" "paginaInicial" => "7" "paginaFinal" => "12" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21951964" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.ejphar.2011.09.012" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.ejphar.2011.09.012" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib25" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence of Hospitalization for Vaccine-Preventable Infections in Children Following Solid Organ Transplant and Associated Morbidity, Mortality, and Costs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ AG Feldman \n \t\t\t\t\t\t\t\t """ 1 => """ BL Beaty \n \t\t\t\t\t\t\t\t """ 2 => """ D Curtis \n \t\t\t\t\t\t\t\t """ 3 => """ E Juarez-Colunga \n \t\t\t\t\t\t\t\t """ 4 => """ A Kempe \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1001/jamapediatrics.2018.4954" "Revista" => array:7 [ "tituloSerie" => "JAMA Pediatr" "fecha" => "2019" "volumen" => "173" "numero" => "3" "paginaInicial" => "260" "paginaFinal" => "268" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30640369" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1001/jamapediatrics.2018.4954" "WWW" => array:1 [ "link" => "https://doi.org/10.1001/jamapediatrics.2018.4954" ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack638082" "titulo" => "ACKNOWLEDGMENTS" "texto" => "<p id="para280" class="elsevierStylePara elsevierViewall">The authors would like to thank the medical and non-medical staffs of the Second Rehabilitation Hospital of Shanghai, Shanghai, China.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/18075932/000000750000000C/v1_202211290815/S1807593222003052/v1_202211290815/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/18075932/000000750000000C/v1_202211290815/S1807593222003052/v1_202211290815/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222003052?idApp=UINPBA00004N" ]
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2024 June | 28 | 9 | 37 |
2024 May | 22 | 15 | 37 |
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2024 March | 16 | 8 | 24 |
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2023 April | 34 | 3 | 37 |
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