Editorial comment
Genomic characterization in dilated cardiomyopathy
Caracterização genómica na cardiomiopatia dilatada
Marina C. Costa
Instituto de Medicina Molecular João Lobo Antunes & Centro Cardiovascular Universidade de Lisboa (CCUL), Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
Lido
3862
Vezesque se leu este artigo
1489
Total PDF
2373
Total HTML
Compartilhar estatísticas
array:25 [ "pii" => "S0870255119304287" "issn" => "08702551" "doi" => "10.1016/j.repc.2019.07.002" "estado" => "S300" "fechaPublicacion" => "2019-06-01" "aid" => "1406" "copyright" => "Sociedade Portuguesa de Cardiologia" "copyrightAnyo" => "2019" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2019;38:449-50" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 587 "formatos" => array:3 [ "EPUB" => 43 "HTML" => 395 "PDF" => 149 ] ] "itemSiguiente" => array:20 [ "pii" => "S0870255118300970" "issn" => "08702551" "doi" => "10.1016/j.repc.2018.06.002" "estado" => "S300" "fechaPublicacion" => "2019-06-01" "aid" => "1264" "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. 2019;38:451-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 797 "formatos" => array:3 [ "EPUB" => 76 "HTML" => 562 "PDF" => 159 ] ] "pt" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artigo Original</span>" "titulo" => "Importância dos dispositivos eletrónicos cardíacos implantáveis no diagnóstico da Síndrome da Apneia do Sono" "tienePdf" => "pt" "tieneTextoCompleto" => "pt" "tieneResumen" => array:2 [ 0 => "pt" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "451" "paginaFinal" => "455" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Importance of cardiac implantable eletronic devices in the diagnosis of Sleep Apnea Syndrome" ] ] "contieneResumen" => array:2 [ "pt" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "pt" => true ] "contienePdf" => array:1 [ "pt" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Sílvia Ribeiro, Laura Bonito, Maria José Guimarães, João Português, Bernardete Rodrigues, Assunção Alves, Célia Durães, Daniela Ferreira, Victor Sanfins, António Lourenço" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Sílvia" "apellidos" => "Ribeiro" ] 1 => array:2 [ "nombre" => "Laura" "apellidos" => "Bonito" ] 2 => array:2 [ "nombre" => "Maria José" "apellidos" => "Guimarães" ] 3 => array:2 [ "nombre" => "João" "apellidos" => "Português" ] 4 => array:2 [ "nombre" => "Bernardete" "apellidos" => "Rodrigues" ] 5 => array:2 [ "nombre" => "Assunção" "apellidos" => "Alves" ] 6 => array:2 [ "nombre" => "Célia" "apellidos" => "Durães" ] 7 => array:2 [ "nombre" => "Daniela" "apellidos" => "Ferreira" ] 8 => array:2 [ "nombre" => "Victor" "apellidos" => "Sanfins" ] 9 => array:2 [ "nombre" => "António" "apellidos" => "Lourenço" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204919301795" "doi" => "10.1016/j.repce.2018.06.013" "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/S2174204919301795?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255118300970?idApp=UINPBA00004E" "url" => "/08702551/0000003800000006/v3_201911281004/S0870255118300970/v3_201911281004/pt/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S0870255117304298" "issn" => "08702551" "doi" => "10.1016/j.repc.2019.02.006" "estado" => "S300" "fechaPublicacion" => "2019-06-01" "aid" => "1402" "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. 2019;38:441-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 721 "formatos" => array:3 [ "EPUB" => 52 "HTML" => 522 "PDF" => 147 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Genetic variants identified by target next-generation sequencing in heart transplant patients with dilated cardiomyopathy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "441" "paginaFinal" => "447" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Variantes genéticas utilizando sequenciação de nova geração em doentes submetidos a transplante cardíaco" ] ] "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" => 369 "Ancho" => 1405 "Tamanyo" => 105451 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Patient 3: baseline 12-lead electrocardiogram and 24-hour Holter monitoring showing left ventricular hypertrophy (A) and runs of nonsustained ventricular tachycardia (B).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Elisabete Martins, Alexandra Sousa, Paulo Canedo, Sérgio Leite, Roberto Pinto, Manuel Campelo, Sandra Amorim, Brenda Moura, José Manuel Lopes, José Carlos Machado, José Silva Cardoso" "autores" => array:12 [ 0 => array:2 [ "nombre" => "Elisabete" "apellidos" => "Martins" ] 1 => array:2 [ "nombre" => "Alexandra" "apellidos" => "Sousa" ] 2 => array:2 [ "nombre" => "Paulo" "apellidos" => "Canedo" ] 3 => array:2 [ "nombre" => "Sérgio" "apellidos" => "Leite" ] 4 => array:2 [ "nombre" => "Roberto" "apellidos" => "Pinto" ] 5 => array:2 [ "nombre" => "Manuel" "apellidos" => "Campelo" ] 6 => array:2 [ "nombre" => "Sandra" "apellidos" => "Amorim" ] 7 => array:2 [ "nombre" => "Brenda" "apellidos" => "Moura" ] 8 => array:2 [ "nombre" => "José Manuel" "apellidos" => "Lopes" ] 9 => array:2 [ "nombre" => "José Carlos" "apellidos" => "Machado" ] 10 => array:2 [ "nombre" => "José" "apellidos" => "Silva Cardoso" ] 11 => array:1 [ "colaborador" => "on behalf of the FATIMA investigators" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S217420491930176X" "doi" => "10.1016/j.repce.2019.07.002" "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/S217420491930176X?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117304298?idApp=UINPBA00004E" "url" => "/08702551/0000003800000006/v3_201911281004/S0870255117304298/v3_201911281004/en/main.assets" ] "asociados" => array:1 [ 0 => array:20 [ "pii" => "S0870255117304298" "issn" => "08702551" "doi" => "10.1016/j.repc.2019.02.006" "estado" => "S300" "fechaPublicacion" => "2019-06-01" "aid" => "1402" "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. 2019;38:441-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 721 "formatos" => array:3 [ "EPUB" => 52 "HTML" => 522 "PDF" => 147 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Genetic variants identified by target next-generation sequencing in heart transplant patients with dilated cardiomyopathy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "441" "paginaFinal" => "447" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Variantes genéticas utilizando sequenciação de nova geração em doentes submetidos a transplante cardíaco" ] ] "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" => 369 "Ancho" => 1405 "Tamanyo" => 105451 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Patient 3: baseline 12-lead electrocardiogram and 24-hour Holter monitoring showing left ventricular hypertrophy (A) and runs of nonsustained ventricular tachycardia (B).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Elisabete Martins, Alexandra Sousa, Paulo Canedo, Sérgio Leite, Roberto Pinto, Manuel Campelo, Sandra Amorim, Brenda Moura, José Manuel Lopes, José Carlos Machado, José Silva Cardoso" "autores" => array:12 [ 0 => array:2 [ "nombre" => "Elisabete" "apellidos" => "Martins" ] 1 => array:2 [ "nombre" => "Alexandra" "apellidos" => "Sousa" ] 2 => array:2 [ "nombre" => "Paulo" "apellidos" => "Canedo" ] 3 => array:2 [ "nombre" => "Sérgio" "apellidos" => "Leite" ] 4 => array:2 [ "nombre" => "Roberto" "apellidos" => "Pinto" ] 5 => array:2 [ "nombre" => "Manuel" "apellidos" => "Campelo" ] 6 => array:2 [ "nombre" => "Sandra" "apellidos" => "Amorim" ] 7 => array:2 [ "nombre" => "Brenda" "apellidos" => "Moura" ] 8 => array:2 [ "nombre" => "José Manuel" "apellidos" => "Lopes" ] 9 => array:2 [ "nombre" => "José Carlos" "apellidos" => "Machado" ] 10 => array:2 [ "nombre" => "José" "apellidos" => "Silva Cardoso" ] 11 => array:1 [ "colaborador" => "on behalf of the FATIMA investigators" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S217420491930176X" "doi" => "10.1016/j.repce.2019.07.002" "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/S217420491930176X?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117304298?idApp=UINPBA00004E" "url" => "/08702551/0000003800000006/v3_201911281004/S0870255117304298/v3_201911281004/en/main.assets" ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Genomic characterization in dilated cardiomyopathy" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "449" "paginaFinal" => "450" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Marina C. Costa" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Marina C." "apellidos" => "Costa" "email" => array:1 [ 0 => "marinacosta@medicina.ulisboa.pt" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Instituto de Medicina Molecular João Lobo Antunes & Centro Cardiovascular Universidade de Lisboa (CCUL), Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Caracterização genómica na cardiomiopatia dilatada" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Dilated cardiomyopathy (DCM), a leading cause of heart failure and sudden cardiac death, is characterized by ventricular dilatation and impaired systolic function in the absence of abnormal loading conditions or coronary artery disease.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Its prevalence is approximately 1 in 2500 individuals, and 30-50% of cases are familial.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Familial DCM is a predominantly autosomal disease with dominant transmission, although autosomal recessive, X-linked and mitochondrial patterns of inheritance have also been described.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> In familial DCM, nearly 60% of cases display some form of mutation in one of more than 60 genes associated with DCM.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Pathogenic variants in the gene coding for the titin protein (<span class="elsevierStyleItalic">TTN</span>) appear to be the main cause of familial DCM, being reported in 12-25% of cases.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3–5</span></a> The second most prevalent gene in familial DCM (<span class="elsevierStyleItalic">LMNA</span>) codes for lamin A/C, variants of which are found in around 10-15% of cases.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a> DCM patients with <span class="elsevierStyleItalic">LMNA</span> mutations are reported to have worse prognosis and more serious cardiovascular complications, including sudden cardiac death and a higher rate of heart transplantation (HT), compared to individuals with idiopathic DCM.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Other genes, including those for beta-myosin heavy chain 7 (<span class="elsevierStyleItalic">MYH7</span>), cardiac troponin T type 2 (<span class="elsevierStyleItalic">TNNT2</span>), RNA-binding motif protein 20 (<span class="elsevierStyleItalic">RBM20</span>), Bcl2-associated athanogene 3 (<span class="elsevierStyleItalic">BAG3</span>), tropomyosin alpha-1 (<span class="elsevierStyleItalic">TPM1</span>), desmoplakin (<span class="elsevierStyleItalic">DSP</span>), calcium/sodium-handling proteins of sodium channel type V alpha subunit (<span class="elsevierStyleItalic">SCN5A</span>), cardiac muscle alpha actin 1 (<span class="elsevierStyleItalic">ACTC1</span>) and cardiac myosin-binding protein C (<span class="elsevierStyleItalic">MYBPC3</span>), appear to be involved in 5-10% cases of familial DCM.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> This genetic diversity in DCM has significant implications for molecular diagnosis and clinical genetic counseling.</p><p id="par0015" class="elsevierStylePara elsevierViewall">DCM can progress to a terminal stage due to various factors such as the aggressiveness of the disease, late initiation of pharmacotherapy, or, especially, the presence of an adverse genetic background and its relationship with environmental factors. These patients may eventually progress to HT, regardless of therapy. In this context, genetic characterization can be a useful tool to determine the mechanisms that result in failure to respond to heart failure therapies and progression to terminal disease.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the current issue of the <span class="elsevierStyleItalic">Journal</span>, Martins et al.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> analyze thirteen HT recipients with end-stage DCM. In this group, they screened for mutations in 15 genes – <span class="elsevierStyleItalic">LMNA</span>/C, <span class="elsevierStyleItalic">MYH7</span>, <span class="elsevierStyleItalic">MYBPC3</span>, <span class="elsevierStyleItalic">TNNT2</span>, <span class="elsevierStyleItalic">ACTA1</span>, <span class="elsevierStyleItalic">TPM1</span>, <span class="elsevierStyleItalic">CSRP3</span>, <span class="elsevierStyleItalic">TCAP</span>, <span class="elsevierStyleItalic">SGCD</span>, <span class="elsevierStyleItalic">PLN</span>, <span class="elsevierStyleItalic">MYL2</span>, <span class="elsevierStyleItalic">MYL3</span>, <span class="elsevierStyleItalic">TNNI3</span>, <span class="elsevierStyleItalic">TAZ</span> and <span class="elsevierStyleItalic">LDB3</span>. The genetic characterization was carried out using next-generation sequencing (NGS), which identified nine variants in six (46%) patients: five in <span class="elsevierStyleItalic">LMNA</span>, two in <span class="elsevierStyleItalic">LBD3</span>, one in <span class="elsevierStyleItalic">TNNT2</span> and one in <span class="elsevierStyleItalic">TCAP.</span> Most of these variations were considered non-pathogenic or of uncertain significance, except for one variant in <span class="elsevierStyleItalic">LMNA</span> that was classified as likely pathogenic (c.1003C>T; p.Arg335Trp).</p><p id="par0025" class="elsevierStylePara elsevierViewall">The study by Martins et al. presents some limitations that are clearly stated by the authors, including the small numbers of patients and of genes studied, which limit the study's conclusions. Nevertheless, the paper accurately depicts the genetic variation of DCM-related genes in a Portuguese patient cohort and highlights the importance of genetic characterization in HT recipients due to end-stage DCM, stressing the need for further studies.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Previously, clinical genetic testing was mainly based on conventional molecular techniques like Sanger sequencing, but recent advances in DNA and RNA sequencing technology mean that larger numbers of genes can now be studied simultaneously.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> The high-throughput sequencing methods of NGS are able to rapidly analyze a large number of genetic loci and samples. The data thus generated provide researchers and clinicians with an assortment of tools to study genomes in greater depth and can lead to a better understanding of genomic variation, phenotype and disease. Consequently, whole-exome and genome sequencing for clinical screening are currently entering clinical practice in various medical specialties, particularly in cardiology.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> The application of NGS technology in genetic analysis, together with a better knowledge of the DCM phenotype, will help to improve diagnosis, prognosis and risk stratification. It may contribute to our knowledge of the genetic mechanisms of cardiomyopathies that do not respond to medical therapy, which includes DCM patients undergoing HT.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0035" 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:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases" "etal" => true "autores" => array:3 [ 0 => "P. Elliott" 1 => "B. Andersson" 2 => "E. Arbustini" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehm342" "Revista" => array:7 [ "tituloSerie" => "Eur Heart J" "fecha" => "2008" "volumen" => "29" "paginaInicial" => "270" "paginaFinal" => "276" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17916581" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0168827811000274" "estado" => "S300" "issn" => "01688278" ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0060" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Atlas of the clinical genetics of human dilated cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J. Haas" 1 => "K.S. Frese" 2 => "B. Peil" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehu301" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2015" "volumen" => "36" "paginaInicial" => "1123" "paginaFinal" => "1135" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25163546" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0065" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dilated cardiomyopathy: genetic determinants and mechanisms" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E.M. McNally" 1 => "L. Mestroni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCRESAHA.116.309396" "Revista" => array:6 [ "tituloSerie" => "Circ Res" "fecha" => "2017" "volumen" => "121" "paginaInicial" => "731" "paginaFinal" => "748" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28912180" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0070" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Truncations of titin causing dilated cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "D.S. Herman" 1 => "L. Lam" 2 => "M.R. Taylor" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1110186" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "366" "paginaInicial" => "619" "paginaFinal" => "628" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22335739" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0075" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "B. Gerull" 1 => "M. Gramlich" 2 => "J. Atherton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng815" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2002" "volumen" => "30" "paginaInicial" => "201" "paginaFinal" => "204" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11788824" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0080" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quantitative expression of the mutated lamin A/C gene in patients with cardiolaminopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "N. Narula" 1 => "V. Favalli" 2 => "P. Tarantino" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2012.05.059" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2012" "volumen" => "60" "paginaInicial" => "1916" "paginaFinal" => "1920" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23062543" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0085" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lamin A/C mutation analysis in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S.B. Parks" 1 => "J.D. Kushner" 2 => "D. Nauman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ahj.2008.01.026" "Revista" => array:6 [ "tituloSerie" => "Am Heart J" "fecha" => "2008" "volumen" => "156" "paginaInicial" => "161" "paginaFinal" => "169" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18585512" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0090" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Familial dilated cardiomyopathy: a multidisciplinary entity, from basic screening to novel circulating biomarkers" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "D. de Gonzalo-Calvo" 1 => "M. Quezada" 2 => "O. Campuzano" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijcard.2016.11.045" "Revista" => array:6 [ "tituloSerie" => "Int J Cardiol" "fecha" => "2017" "volumen" => "228" "paginaInicial" => "870" "paginaFinal" => "880" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27889554" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0095" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic variants identified by target next generation sequencing in heart transplant patients with dilated cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "E. Martins" 1 => "A. Sousa" 2 => "P. Canedo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.repc.2019.02.006" "Revista" => array:6 [ "tituloSerie" => "Rev Port Cardiol" "fecha" => "2019" "volumen" => "38" "paginaInicial" => "441" "paginaFinal" => "447" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31303467" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0100" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "The current role of next-generation DNA sequencing in routine care of patients with hereditary cardiovascular conditions: a viewpoint paper of the European Society of Cardiology working group on myocardial and pericardial diseases and members of the European Society of Human Genetics" "etal" => true "autores" => array:3 [ 0 => "J. Mogensen" 1 => "J.P. van Tintelen" 2 => "S. Fokstuen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehv122" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2015" "volumen" => "36" "paginaInicial" => "1367" "paginaFinal" => "1370" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25845928" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/08702551/0000003800000006/v3_201911281004/S0870255119304287/v3_201911281004/en/main.assets" "Apartado" => array:4 [ "identificador" => "29261" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Artigos Originais" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/08702551/0000003800000006/v3_201911281004/S0870255119304287/v3_201911281004/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255119304287?idApp=UINPBA00004E" ]
| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 10 | 5 | 15 |
| 2024 Outubro | 51 | 38 | 89 |
| 2024 Setembro | 45 | 24 | 69 |
| 2024 Agosto | 54 | 29 | 83 |
| 2024 Julho | 41 | 30 | 71 |
| 2024 Junho | 43 | 27 | 70 |
| 2024 Maio | 56 | 20 | 76 |
| 2024 Abril | 42 | 31 | 73 |
| 2024 Maro | 42 | 24 | 66 |
| 2024 Fevereiro | 37 | 21 | 58 |
| 2024 Janeiro | 29 | 23 | 52 |
| 2023 Dezembro | 28 | 24 | 52 |
| 2023 Novembro | 29 | 37 | 66 |
| 2023 Outubro | 22 | 20 | 42 |
| 2023 Setembro | 23 | 21 | 44 |
| 2023 Agosto | 24 | 21 | 45 |
| 2023 Julho | 29 | 14 | 43 |
| 2023 Junho | 33 | 12 | 45 |
| 2023 Maio | 31 | 26 | 57 |
| 2023 Abril | 23 | 8 | 31 |
| 2023 Maro | 40 | 16 | 56 |
| 2023 Fevereiro | 37 | 16 | 53 |
| 2023 Janeiro | 26 | 13 | 39 |
| 2022 Dezembro | 31 | 23 | 54 |
| 2022 Novembro | 47 | 24 | 71 |
| 2022 Outubro | 37 | 25 | 62 |
| 2022 Setembro | 26 | 34 | 60 |
| 2022 Agosto | 32 | 33 | 65 |
| 2022 Julho | 26 | 41 | 67 |
| 2022 Junho | 18 | 25 | 43 |
| 2022 Maio | 30 | 27 | 57 |
| 2022 Abril | 37 | 37 | 74 |
| 2022 Maro | 36 | 35 | 71 |
| 2022 Fevereiro | 23 | 33 | 56 |
| 2022 Janeiro | 18 | 31 | 49 |
| 2021 Dezembro | 27 | 23 | 50 |
| 2021 Novembro | 23 | 30 | 53 |
| 2021 Outubro | 27 | 45 | 72 |
| 2021 Setembro | 35 | 32 | 67 |
| 2021 Agosto | 25 | 35 | 60 |
| 2021 Julho | 24 | 22 | 46 |
| 2021 Junho | 25 | 21 | 46 |
| 2021 Maio | 24 | 26 | 50 |
| 2021 Abril | 34 | 38 | 72 |
| 2021 Maro | 42 | 27 | 69 |
| 2021 Fevereiro | 47 | 15 | 62 |
| 2021 Janeiro | 33 | 17 | 50 |
| 2020 Dezembro | 23 | 12 | 35 |
| 2020 Novembro | 32 | 12 | 44 |
| 2020 Outubro | 43 | 16 | 59 |
| 2020 Setembro | 25 | 16 | 41 |
| 2020 Agosto | 33 | 11 | 44 |
| 2020 Julho | 23 | 10 | 33 |
| 2020 Junho | 27 | 14 | 41 |
| 2020 Maio | 40 | 9 | 49 |
| 2020 Abril | 79 | 11 | 90 |
| 2020 Maro | 101 | 21 | 122 |
| 2020 Fevereiro | 105 | 40 | 145 |
| 2020 Janeiro | 23 | 12 | 35 |
| 2019 Dezembro | 40 | 9 | 49 |
| 2019 Novembro | 17 | 11 | 28 |
| 2019 Outubro | 37 | 24 | 61 |
| 2019 Setembro | 117 | 19 | 136 |
| 2019 Agosto | 47 | 11 | 58 |
| 2019 Julho | 39 | 32 | 71 |
Mostrar tudo
