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array:25 [ "pii" => "S2174204918304197" "issn" => "21742049" "doi" => "10.1016/j.repce.2018.12.007" "estado" => "S300" "fechaPublicacion" => "2018-12-01" "aid" => "1326" "copyrightAnyo" => "2018" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2018;37:971-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 443 "formatos" => array:3 [ "EPUB" => 77 "HTML" => 209 "PDF" => 157 ] ] "Traduccion" => array:1 [ "en" => array:20 [ "pii" => "S0870255117308120" "issn" => "08702551" "doi" => "10.1016/j.repc.2018.02.010" "estado" => "S300" "fechaPublicacion" => "2018-12-01" "aid" => "1321" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2018;37:961-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 771 "formatos" => array:3 [ "EPUB" => 88 "HTML" => 443 "PDF" => 240 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Impact on long-term cardiovascular outcomes of different cardiac resynchronization therapy response criteria" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "961" "paginaFinal" => "969" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Impacto dos diferentes critérios de resposta à terapia de ressincronização nos eventos cardiovasculares a longo prazo" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1400 "Ancho" => 1480 "Tamanyo" => 269238 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Agreement between response criteria was strong in only 7.6% of response criteria pairs. Cohen's κ values are color-coded according to the following ranges: dark gray=strong agreement (κ ≥0.75), light gray=moderate agreement (κ 0.4-0.75), none=poor agreement (κ ≤0.4). ↑: higher: ↓: lower; Comb: combined; HF: heart failure; LVEDV: left ventricular end-diastolic volume; LVEF: left ventricular ejection fraction; LVESV: left ventricular end-systolic volume; NYHA: New York Heart Association functional class; peak VO<span class="elsevierStyleInf">2</span>: oxygen consumption at peak exercise; QoL: HeartQoL quality-of-life score.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Inês Rodrigues, Ana Abreu, Mário Oliveira, Pedro S. Cunha, Helena Santa Clara, Paulo Osório, Ana Lousinha, Bruno Valente, Guilherme Portugal, Pedro Rio, Luís A. Morais, Vanessa Santos, Miguel M. Carmo, Rui C. Ferreira" "autores" => array:14 [ 0 => array:2 [ "nombre" => "Inês" "apellidos" => "Rodrigues" ] 1 => array:2 [ "nombre" => "Ana" "apellidos" => "Abreu" ] 2 => array:2 [ "nombre" => "Mário" "apellidos" => "Oliveira" ] 3 => array:2 [ "nombre" => "Pedro S." "apellidos" => "Cunha" ] 4 => array:2 [ "nombre" => "Helena Santa" "apellidos" => "Clara" ] 5 => array:2 [ "nombre" => "Paulo" "apellidos" => "Osório" ] 6 => array:2 [ "nombre" => "Ana" "apellidos" => "Lousinha" ] 7 => array:2 [ "nombre" => "Bruno" "apellidos" => "Valente" ] 8 => array:2 [ "nombre" => "Guilherme" "apellidos" => "Portugal" ] 9 => array:2 [ "nombre" => "Pedro" "apellidos" => "Rio" ] 10 => array:2 [ "nombre" => "Luís A." "apellidos" => "Morais" ] 11 => array:2 [ "nombre" => "Vanessa" "apellidos" => "Santos" ] 12 => array:2 [ "nombre" => "Miguel M." "apellidos" => "Carmo" ] 13 => array:2 [ "nombre" => "Rui C." "apellidos" => "Ferreira" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204918304197" "doi" => "10.1016/j.repce.2018.12.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204918304197?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117308120?idApp=UINPBA00004E" "url" => "/08702551/0000003700000012/v3_201911281020/S0870255117308120/v3_201911281020/en/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2174204918304203" "issn" => "21742049" "doi" => "10.1016/j.repce.2018.01.011" "estado" => "S300" "fechaPublicacion" => "2018-12-01" "aid" => "1320" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2018;37:973-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 559 "formatos" => array:3 [ "EPUB" => 111 "HTML" => 249 "PDF" => 199 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Health care cost analysis of enhanced pacing modalities in bradycardia patients: Portuguese case study on the results of the MINERVA trial" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "973" "paginaFinal" => "978" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Análise de redução de custos por utilização de novos algoritmos de <span class="elsevierStyleItalic">pacing</span> em doentes com bradicardia: estudo de caso português com os resultados do estudo MINERVA" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1085 "Ancho" => 2074 "Tamanyo" => 129444 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Scheme of cost-saving analysis.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "João de Sousa, Pedro Marques, Vítor Martins, António Hipólito-Reis, Luís Duarte, Inês Joaquim, Diogo Monteiro, Giuseppe Boriani, Claudia Wolff, Andrea Grammatico, Luigi Padeletti" "autores" => array:11 [ 0 => array:2 [ "nombre" => "João" "apellidos" => "de Sousa" ] 1 => 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diferentes critérios de resposta à terapia de ressincronização nos eventos cardiovasculares a longo prazo" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3006 "Ancho" => 2513 "Tamanyo" => 376454 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Survival curves of cumulative occurrence of major adverse cardiac events in responders or non-responders to cardiac resynchronization therapy according to the most strongly predictive response criteria. (A) Criterion of ↓NYHA ≥1; (B) criterion of ↓NYHA ≥1 or ↑peak VO2>10% and alive, no hospitalization for heart failure; (C) criterion of ↑LVEF ≥5% (absolute); (D) criterion of ↑LVEF ≥15%; (E) criterion of ↑LVEF ≥5% (absolute) and ↓NYHA ≥1 or ↑HeartQoL ≥0.5. ↑: higher: ↓: lower; CI: confidence interval; CRT: cardiac resynchronization therapy; HF: heart failure; HR: hazard ratio; LVEF: left ventricular ejection fraction; NYHA: New York Heart Association functional class; QoL: HeartQoL quality-of-life score.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Inês Rodrigues, Ana Abreu, Mário Oliveira, Pedro S. Cunha, Helena Santa Clara, Paulo Osório, Ana Lousinha, Bruno Valente, Guilherme Portugal, Pedro Rio, Luís A. Morais, Vanessa Santos, Miguel M. Carmo, Rui C. 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"apellidos" => "Ferreira" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204918304185?idApp=UINPBA00004E" "url" => "/21742049/0000003700000012/v1_201812280741/S2174204918304185/v1_201812280741/en/main.assets" ] "asociados" => array:1 [ 0 => array:19 [ "pii" => "S2174204918304185" "issn" => "21742049" "doi" => "10.1016/j.repce.2018.02.021" "estado" => "S300" "fechaPublicacion" => "2018-12-01" "aid" => "1321" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2018;37:961-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 573 "formatos" => array:3 [ "EPUB" => 93 "HTML" => 306 "PDF" => 174 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Impact on long-term cardiovascular outcomes of different cardiac resynchronization therapy response criteria" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "961" "paginaFinal" => "969" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Impacto dos diferentes critérios de resposta à terapia de ressincronização nos eventos cardiovasculares a longo prazo" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3006 "Ancho" => 2513 "Tamanyo" => 376454 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Survival curves of cumulative occurrence of major adverse cardiac events in responders or non-responders to cardiac resynchronization therapy according to the most strongly predictive response criteria. (A) Criterion of ↓NYHA ≥1; (B) criterion of ↓NYHA ≥1 or ↑peak VO2>10% and alive, no hospitalization for heart failure; (C) criterion of ↑LVEF ≥5% (absolute); (D) criterion of ↑LVEF ≥15%; (E) criterion of ↑LVEF ≥5% (absolute) and ↓NYHA ≥1 or ↑HeartQoL ≥0.5. ↑: higher: ↓: lower; CI: confidence interval; CRT: cardiac resynchronization therapy; HF: heart failure; HR: hazard ratio; LVEF: left ventricular ejection fraction; NYHA: New York Heart Association functional class; QoL: HeartQoL quality-of-life score.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Inês Rodrigues, Ana Abreu, Mário Oliveira, Pedro S. Cunha, Helena Santa Clara, Paulo Osório, Ana Lousinha, Bruno Valente, Guilherme Portugal, Pedro Rio, Luís A. Morais, Vanessa Santos, Miguel M. Carmo, Rui C. Ferreira" "autores" => array:14 [ 0 => array:2 [ "nombre" => "Inês" "apellidos" => "Rodrigues" ] 1 => array:2 [ "nombre" => "Ana" "apellidos" => "Abreu" ] 2 => array:2 [ "nombre" => "Mário" "apellidos" => "Oliveira" ] 3 => array:2 [ "nombre" => "Pedro S." "apellidos" => "Cunha" ] 4 => array:2 [ "nombre" => "Helena Santa" "apellidos" => "Clara" ] 5 => array:2 [ "nombre" => "Paulo" "apellidos" => "Osório" ] 6 => array:2 [ "nombre" => "Ana" "apellidos" => "Lousinha" ] 7 => array:2 [ "nombre" => "Bruno" "apellidos" => "Valente" ] 8 => array:2 [ "nombre" => "Guilherme" "apellidos" => "Portugal" ] 9 => array:2 [ "nombre" => "Pedro" "apellidos" => "Rio" ] 10 => array:2 [ "nombre" => "Luís A." "apellidos" => "Morais" ] 11 => array:2 [ "nombre" => "Vanessa" "apellidos" => "Santos" ] 12 => array:2 [ "nombre" => "Miguel M." "apellidos" => "Carmo" ] 13 => array:2 [ "nombre" => "Rui C." "apellidos" => "Ferreira" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204918304185?idApp=UINPBA00004E" "url" => "/21742049/0000003700000012/v1_201812280741/S2174204918304185/v1_201812280741/en/main.assets" ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Assessing response to cardiac resynchronization therapy: Time to settle on some definitive criteria" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "971" "paginaFinal" => "972" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Leonor Parreira" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Leonor" "apellidos" => "Parreira" "email" => array:1 [ 0 => "leonor.parreira@gmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Serviço de Cardiologia, Centro Hospitalar de Setúbal, Setúbal, Portugal" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Avaliação da resposta à terapêutica de ressincronização cardíaca. É necessário estabelecer critérios definitivos" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Cardiac resynchronization therapy (CRT) is a 20-year-old technology. Since its introduction, there has been considerable debate about the non-response rate, especially in view of the initial cost of the system and the need for a surgical procedure to implant it. In fact, the non-response rate, generally around 30%, is not so different from that of other therapies for heart failure (HF).</p><p id="par0010" class="elsevierStylePara elsevierViewall">There is much confusion about response to CRT. Firstly, it is highly dependent on the criteria used to define response; studies have shown that response rates range from 32% to 91% depending on the criteria used.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Rates tend to be higher when subjective clinical measures are used, but much lower on outcome measures. Secondly, there is disagreement between different methods of assessing response. The lack of correlation between different ways of defining success, and their association with prognosis in terms of decreased mortality and morbidity, was first addressed by Yu et al.,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> who demonstrated that increase in left ventricular ejection fraction (LVEF) was associated with longer survival but not with improvement in symptoms.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Subsequently, Cha et al.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> concluded otherwise, demonstrating that clinical improvement influenced outcome but that reverse remodeling was not needed for this survival benefit.</p><p id="par0020" class="elsevierStylePara elsevierViewall">It is necessary to decide which should be defined as response to CRT: living better or living longer.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The class I indication for CRT in HF was based not on improvement in symptoms or exercise capacity, but on its effect on mortality or morbidity. The ultimate response to CRT should accordingly be a decrease in mortality and morbidity, i.e. fewer HF events. All other clinical, echocardiographic or laboratory improvements are merely surrogate markers of the real response. Any attempt to predict outcome by means of clinical or echocardiographic surrogates is hampered by its subjective nature. Although non-responders usually have worse outcomes than responders, this is not always the case.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Finally, there is an additional issue to consider when using surrogate markers of outcome, which is the timing to assess results and cutoff values.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In addition to the above, HF is a progressive disease, so many factors may influence outcome, not only CRT response.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In this issue of the <span class="elsevierStyleItalic">Journal</span>, Rodrigues et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> chose eleven criteria used in previous CRT trials and assessed the accuracy of each of these criteria alone and in combination for predicting survival free from major adverse cardiac events (MACE). They found that the only three isolated criteria that could predict outcome were a clinical criterion (a decrease of at least one New York Heart Association [NYHA] functional class) and two echocardiographic parameters, reflecting an absolute and a relative increase in LVEF. No other criteria were able to predict outcome. However, even these three were not ideal: a reduction of ≥1 NYHA functional class showed an unadjusted reduction of 61% in the probability of MACE, and a >15% increase in LVEF showed an unadjusted reduction of 57%.</p><p id="par0045" class="elsevierStylePara elsevierViewall">One of the disadvantages of clinical criteria is the subjective nature of their measurement, which depends on the patient's or physician's point of view, but this study demonstrates that measurement of peak oxygen consumption (pVO<span class="elsevierStyleInf">2</span>) was less accurate than reduction in NYHA class. When no hospitalization for HF within six months was added to reduced NYHA class and increased pVO<span class="elsevierStyleInf">2</span>, the risk reduction was 79%, highlighting the superiority of an objective clinical criterion (absence of hospitalization).</p><p id="par0050" class="elsevierStylePara elsevierViewall">Composite endpoints are often used in clinical trials of CRT. However, they are only reliable when each component is of similar importance, and previous studies have shown that combining parameters, which complicates the reporting of results, does not increase accuracy.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In my opinion, it would have been useful if this paper had assessed adjusted hazard ratios, at least with the more representative variables. The authors did not test interactions between the criteria considered and prognostic parameters such as age, QRS duration, serum creatinine, B-type natriuretic peptide and HF etiology. Boidol et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> showed that response criteria have different predictive power in different patient subgroups depending on baseline characteristics. Similarly, Rodrigues et al. highlight the lack of agreement between different criteria; in their study only three criteria (5.5%) had Cohen's kappa (κ) values in the range of strong agreement. More worrisome is the lack of correlation between the two most accurate criteria (κ 0.20 between >1 reduction in NYHA class and >5% absolute increase in LVEF), which calls into question the usefulness of comparing studies using different criteria.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Another important issue is the timing of response assessment. In Rodrigues et al.’s study, the second echocardiogram was performed six months after CRT. It is now known that late reverse remodeling occurs in some patients,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> the effect of which on survival is similar to that of early reverse remodeling. It therefore cannot be ruled out that some of the echocardiographic non-responders in this study may have been late responders.</p><p id="par0065" class="elsevierStylePara elsevierViewall">This paper highlights the fallacy of cataloging patients into categories according to clinical or echocardiographic response criteria. However, at times some way of assessing CRT response is necessary in order to assess the need to optimize device programming, and this paper demonstrates that simple criteria like increased LVEF and decreased NYHA class may be suitable for this purpose.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Nevertheless, it is important to remember that response to CRT should always be based on hard endpoints, namely improved survival and reduction of HF events, rather than on surrogate endpoints.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Agreement is poor among current criteria used to define response to cardiac resynchronization therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "B. 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