Editorial
The implementation of cardionephrology in Spain is a health emergency
La implantación de la cardionefrología en España es una urgencia sanitaria
a Servicio de Nefrología, Hospital Universitario de la Princesa, Madrid, Spain
b Red de Investigación Cooperativa Orientada a Resultados en Salud RICORS2040 (Kidney Disease), Spain
c Grupo de Medicina Cardiorrenal de la SEN (CaReSEN), Spain
d Centro de Investigación Médica Aplicada (CIMA) y Facultad de Medicina de la Universidad de Navarra, Pamplona, Spain
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Javier Díez" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Borja" "apellidos" => "Quiroga" "email" => array:1 [ 0 => "borjaqg@gmail.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Javier" "apellidos" => "Díez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 2 => array:2 [ "colaborador" => "en representación del grupo CaReSEN" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario de la Princesa, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Red de Investigación Cooperativa Orientada a Resultados en Salud RICORS2040 (Kidney Disease), Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Grupo de Medicina Cardiorrenal de la SEN (CaReSEN), Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Centro de Investigación Médica Aplicada (CIMA) y Facultad de Medicina de la Universidad de Navarra, Pamplona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La implantación de la cardionefrología en España es una urgencia sanitaria" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The recently published <span class="elsevierStyleItalic">Heart and Kidney Audit</span> (HAKA) study<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> revealed the current situation of medical care of cardiorenal patients with advanced chronic kidney disease (ACKD) being followed in specialized clinics of advanced chronic kidney patients in Spain. This study included 29 ACKD units in the country with a total of 5012 patients (77% with CKD stage G4 and 23% with CKD stage G5), between January and March of 2021. The aim was to analyze the diagnosis and treatment of heart failure (HF) according to the 2016 European Society of Cardiology guidelines, then in force.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> These guidelines recommended diagnosis based on clinical findings, circulating biomarkers and imaging. Likewise, the guidelines recommended treatment of HF with reduced ventricular ejection fraction (EF) based on the combination of a renin-angiotensin system inhibitor (RAASI) or an antagonist of angiotensin receptor and a neprilysin inhibitor (ARNi), with a beta-blocker (BB) and with a antagonist of mineralocorticoid receptor (MRA). Key trials of sodium-glucose cotransporter type 2 (SGLT2) inhibitor drugs demonstrating a reduction in cardiac and renal events in patients with HF and reduced EF had been published already, prompting their addition to the three types of drugs mentioned above to treat these patients.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Results from the HAKA studies are worrisome. First, the diagnosis of HF in patients with ACKD is not based on the obligatory combination of the three classic criteria: clinical manifestations, biomarkers (natriuretic peptides [NP]), and echocardiographic parameters. Since NPs levels can be elevated in ACKD due to the reduction in renal clearance,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> they lose diagnostic specificity, and it is understandable that in the HAKA study they were measured only in 50% of patients.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However, it should not be forgotten that NPs continue to be predictors of cardiac events in patients with ACKD, so to exclude their measurement is not a valid option.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In these circumstances, the most reasonable approach is a correct interpretation of the measured values that includes variations over the baseline values and includes different reference concentrations for patients with ACKD.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Given the diagnostic limitation of the NPs, the use of the other two types of criteria for the diagnosis of HF in patients with ACKD are of greater relevance. The HAKA study<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> showed that the assessment of clinical signs and symptoms and echocardiographic parameters was only performed in 84% and 75% of patients, respectively. It is also true that there are difficulties in clinical and echocardiographic assessment in patients with HF and renal failure<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>; still they should be performed in 100% of cases.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Secondly, the prevalence of HF diagnosed in patients in ACKD units in Spain is very low. Specifically, the diagnosis of HF in the HAKA study<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> was 13% (median), a percentage three times lower than that obtained in the largest series published to date such as the 2020 report of the US Renal Data System.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Of note is the great diagnostic variability observed in the HAKA study,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> with 10 centers with a diagnosed incidence equal to or lower than 10% and four centers with incidence equal to or greater than 30%. In view of the overall prevalence data and as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, it could be stated that the HAKA study<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> shows that in the period evaluated and in the participating centers as a whole, of the 5012 patients with ACKD included, 1522 patients were not diagnosed with HF and likely they had it. Taking into account the most recent study on CKD epidemiology in Spain, which establishes that there were 90,975 patients with ACKD,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> the extrapolation of the above data to the entire country as a whole means that 27,643 patients with ACKD who most probably had HF were not diagnosed with this syndrome in the period during which the study was carried out (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Thirdly, with regard to the treatment of HF, focusing the analysis on patients with HF and reduced EF, the data from the HAKA study<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> are also striking. Out from the 108 patients diagnosed, only 35% received the triple combination RAASI/ARNi + BB + MRA and only an additional 8% received SGLT2 inhibitors in addition to these three drugs. We must add that a minority of patients were treated with the optimal recommended doses of the different drugs (in stage 4 patients 6% received ARNi and 32% received BB, and in stage 5 patients a 6% received ARNi and 39% were on BB). Thus, in the HAKA study<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> more than half (57%) of the patients with ACKD and HF with reduced EF were not treated adequately. The limitation in this interpretation lies in the fact that in this population it is especially difficult to achieve full doses of some drugs and side effects are more frequent. In any case, if this result is extrapolated to the data in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, it could be estimated that out of the 1931 patients with ACKD diagnosed with HF and reduced EF on medication, only 831 would have been appropriately treated. All these data should be weighted taking into account that patients with ACKD have been systematically excluded from the large randomized clinical trials that have made an impact in the treatment of HF with reduced EF.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a> However, in the most recent trials with SGLT2 inhibitors the diagnosis of ACKD (especially in stage G4) is no longer a major exclusion criterion given the cardiac and renal efficacy and safety demonstrated in these more recent trials.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In summary, even with the limitations of an observational and retrospective study such as HAKA,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> the results discussed in this manuscript indicate that more than 3 years ago there was a significant underdiagnosis and very suboptimal treatment of HF in patients with ACKD in Spain. The clinical and health consequences of this situation can be easily deduced from the published evidence on the prognostic impact and economic costs of HF in patients with CKD in general, and particularly in patients with ACKD. For example, over a 2-year period the probability of survival (adjusted for multiple factors) of patients with CKD and HF is 77.85%, 90.2% in patients with CKD without HF and 93.7% in subjects without CKD or HF.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Specifically, patients with CKD and HF have an increased relative risk of cardiovascular mortality and hospitalizations due to HF itself, which is higher in patients with ACKD than in those without ACKD.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Additionally, between 2020 and 2030 the cost of care for patients with CKD and HF will increase by 143%, without taking into account patients on renal replacement therapy, which would increase the cost even further.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Therefore, it can be concluded that three years ago cardionephrology had a limited implementation, which had a direct impact on the inadequate management of patients with cardiorenal involvement, specifically patients with ACKD and HF. It is therefore necessary and urgent to develop new cardiorenal units aiming to improve the diagnosis, treatment and prognosis of these patients, as well as reducing the costs of their care.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> These units should also aim to prevent the onset and progression of cardiovascular disease from the early stages of CKD. As has just been shown in an study that examined data from 61 cohorts including 24,603,016 subjects from all over the world, the relative risk of HF essentially increases by 200% in subjects with estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m<span class="elsevierStyleSup">2</span> and urine albumin-to- creatinine ratio(Au/Cru) values between 30 and 299 mg/g, and increases by up to 40% in subjects with A<span class="elsevierStyleInf">o</span> /Cr<span class="elsevierStyleInf">o</span> < 30 mg/g and GFR values between 60 and 89 mL/min/1.73 m<span class="elsevierStyleSup">2</span>.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The medical and health care of cardiorenal patients is a medical and health care need that has not been adequately accomplished in our country; thus the authors of this editorial, on behalf of the Cardiorenal Medicine Working Group of the Spanish Society of Nephrology (CaReSEN), call for the urgent implementation of cardionephrology in undergraduate programs in medical schools and postgraduate programs in specialist training, and in hospitals and health care centers. We are convinced that these measures will make it possible that in a future HAKA 2 study, the results of the diagnosis and treatment of HF in patients with ACKD will be comparable with what the evidence available indicates they should be.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financing</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have not received funding for this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financing" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">More information about the CaReSEN Group is available in the <a class="elsevierStyleCrossRef" href="#sec0010">Annex</a>.</p>" "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0050" class="elsevierStylePara elsevierViewall">The CaReSEN Working Group is formed by: Javier Díez, Borja Quiroga, Rafael Santamaría, Patricia de Sequera, Alberto Ortiz, Juan Navarro, M. Fernanda Slon and Gregorio Romero.</p>" "etiqueta" => "Annex" "titulo" => "CaReSEN Working Group" "identificador" => "sec0010" ] ] ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">ACKD: advanced chronic kidney disease; HAKA: Heart And Kidney Audit; HF: heart failure.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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" style="border-bottom: 2px solid black">Data from the HAKA<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Study \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" style="border-bottom: 2px solid black">Data from the US Renal Data System<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> \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" style="border-bottom: 2px solid black">Difference \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" style="border-bottom: 2px solid black">Data in Spain<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> \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" style="border-bottom: 2px solid black">Data in Spain estimated with the <span class="elsevierStyleItalic">HAKA</span> study<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> \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" style="border-bottom: 2px solid black">Estimated data in Spain according to the US Renal Data System.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> \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" style="border-bottom: 2px solid black">Difference \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-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients with ACKD \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.012 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.975 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients with ACKD and HF \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">532 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.054 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.522 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.656 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.299 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−27.643 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3675191.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Actual data and estimated data on the diagnosis of heart failure in patients with advanced chronic kidney disease.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">ACKD: advanced chronic kidney disease; EF: left ventricular ejection fraction; HAKA: Heart And Kidney Audit; HF: heart failure.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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" style="border-bottom: 2px solid black">Study data<span class="elsevierStyleItalic">HAKA</span><a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> \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" style="border-bottom: 2px solid black">Difference \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" style="border-bottom: 2px solid black">Estimated data in Spain<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>,<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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" style="border-bottom: 2px solid black">Difference \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-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients with ACKD and HF with reduced EF \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">108 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9656 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients with ACKD and HF with reduced EF under treatment<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−70 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1931 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−7725 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3675190.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">With at least three of the four fundamental heart failure drugs.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Assuming a prevalence of 20% of HF patients with reduced EF as in the HAKA study.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Actual data and estimated data for treatment of heart failure with reduced ejection fraction in patients with advanced chronic kidney disease.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:18 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of chronic heart failure in advanced chronic kidney disease: the HAKA multicenter retrospective real-world study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. 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