Case report
Histopathological evidence of Fabry disease in a female patient with left ventricular noncompaction
Evidência histopatológica de doença de Fabry numa doente com não compactação do ventrículo esquerdo
Elisabete Martinsa,
, Teresa Pinhob, Stirling Carpenterc, Sérgio Leiteb, Raquel Garciab, António Madureirad, João Paulo Oliveirae
Autor para correspondência
a Medical School of Porto, Department of Medicine, São João University Hospital, Porto, Portugal
b Cardiology Department, São João University Hospital, Porto, Portugal
c Pathology Department, São João University Hospital, Porto, Portugal
d Radiology Department, São João University Hospital, Porto, Portugal
e Medical School of Porto, Genetics Department, São João University Hospital, Porto, Portugal
Lido
9069
Vezesque se leu este artigo
2093
Total PDF
6976
Total HTML
Compartilhar estatísticas
array:26 [ "pii" => "S0870255114001851" "issn" => "08702551" "doi" => "10.1016/j.repc.2014.02.021" "estado" => "S300" "fechaPublicacion" => "2014-09-01" "aid" => "503" "copyright" => "Sociedade Portuguesa de Cardiologia" "copyrightAnyo" => "2014" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Rev Port Cardiol. 2014;33:565.e1-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5081 "formatos" => array:3 [ "EPUB" => 173 "HTML" => 4164 "PDF" => 744 ] ] "Traduccion" => array:1 [ "en" => array:19 [ "pii" => "S2174204915000914" "issn" => "21742049" "doi" => "10.1016/j.repce.2015.01.005" "estado" => "S300" "fechaPublicacion" => "2015-04-01" "aid" => "625" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Rev Port Cardiol. 2015;34:299-300" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2198 "formatos" => array:3 [ "EPUB" => 136 "HTML" => 1572 "PDF" => 490 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Noncompaction in Fabry's disease" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "299" "paginaFinal" => "300" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Não compactação na doença de Fabry" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Josef Finsterer, Sinda Zarrouk-Mahjoub, Sonam Kothari" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Josef" "apellidos" => "Finsterer" ] 1 => array:2 [ "nombre" => "Sinda" "apellidos" => "Zarrouk-Mahjoub" ] 2 => array:2 [ "nombre" => "Sonam" "apellidos" => "Kothari" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S087025511500075X" "doi" => "10.1016/j.repc.2015.01.008" "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/S087025511500075X?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204915000914?idApp=UINPBA00004E" "url" => "/21742049/0000003400000004/v2_201504291249/S2174204915000914/v2_201504291249/en/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S0870255114001863" "issn" => "08702551" "doi" => "10.1016/j.repc.2014.03.008" "estado" => "S300" "fechaPublicacion" => "2014-09-01" "aid" => "504" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Rev Port Cardiol. 2014;33:567.e1-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 4325 "formatos" => array:3 [ "EPUB" => 197 "HTML" => 3519 "PDF" => 609 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case report</span>" "titulo" => "A concealed atriopleural fistula resulting from a cardiac stab wound" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "567.e1" "paginaFinal" => "567.e3" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Fístula átrio-pleural/aurículo pleural oculta resultante de uma facada cardíaca penetrante/profunda" ] ] "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" => 1781 "Ancho" => 2500 "Tamanyo" => 487730 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Computed tomography images showing (A) chest stab wound (arrow) and severe secondary right hemothorax with different densities inside suggesting different stages of bleeding (*) and (B) no pericardial effusion; (C) median sternotomy showing parasternal stab wound with no active bleeding (arrow); (D) active bleeding stab wound in the right atrium (arrow); the right lung is covered by the pleura (*); **: pericardial membrane; (E) stab wound in the right atrium sutured with a polypropylene suture buttressed with Teflon felt (arrow). The right lung is visible as the pericardium and right pleura are open (**). RA: right atrium; RL: right lung; RV: right ventricle.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "María Elena Arnáiz-García, Javier Arnáiz, Alejandro Pontón, Ivana Pulitani, Jose María González-Santos, Adolfo Arévalo-Abascal, María E. Bueno-Codoñer, Ana María Arnáiz-García" "autores" => array:8 [ 0 => array:2 [ "nombre" => "María Elena" "apellidos" => "Arnáiz-García" ] 1 => array:2 [ "nombre" => "Javier" "apellidos" => "Arnáiz" ] 2 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Pontón" ] 3 => array:2 [ "nombre" => "Ivana" "apellidos" => "Pulitani" ] 4 => array:2 [ "nombre" => "Jose María" "apellidos" => "González-Santos" ] 5 => array:2 [ "nombre" => "Adolfo" "apellidos" => "Arévalo-Abascal" ] 6 => array:2 [ "nombre" => "María E." "apellidos" => "Bueno-Codoñer" ] 7 => array:2 [ "nombre" => "Ana María" "apellidos" => "Arnáiz-García" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204914002153" "doi" => "10.1016/j.repce.2014.03.010" "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/S2174204914002153?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255114001863?idApp=UINPBA00004E" "url" => "/08702551/0000003300000009/v1_201410010215/S0870255114001863/v1_201410010215/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S0870255114000717" "issn" => "08702551" "doi" => "10.1016/j.repc.2014.02.006" "estado" => "S300" "fechaPublicacion" => "2014-09-01" "aid" => "445" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Rev Port Cardiol. 2014;33:563.e1-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5642 "formatos" => array:3 [ "EPUB" => 179 "HTML" => 4535 "PDF" => 928 ] ] "pt" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Caso clínico</span>" "titulo" => "Estenose aórtica grave: associações esquecidas" "tienePdf" => "pt" "tieneTextoCompleto" => "pt" "tieneResumen" => array:2 [ 0 => "pt" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "563.e1" "paginaFinal" => "563.e4" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Severe aortic stenosis: Forgotten associations" ] ] "contieneResumen" => array:2 [ "pt" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "pt" => true ] "contienePdf" => array:1 [ "pt" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 659 "Ancho" => 975 "Tamanyo" => 76334 ] ] "descripcion" => array:1 [ "pt" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">(paraesternal eixo longo) Válvula aórtica espessada e calcificada, com limitação importante da amplitude de abertura.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Rita Godinho, Sandra Amorim, Manuel Campelo, Elisabete Martins, Elisa Lopez Rodriguez, Rosa Coelho, Guilherme Macedo, Maria Júlia Maciel" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Ana Rita" "apellidos" => "Godinho" ] 1 => array:2 [ "nombre" => "Sandra" "apellidos" => "Amorim" ] 2 => array:2 [ "nombre" => "Manuel" "apellidos" => "Campelo" ] 3 => array:2 [ "nombre" => "Elisabete" "apellidos" => "Martins" ] 4 => array:2 [ "nombre" => "Elisa" "apellidos" => "Lopez Rodriguez" ] 5 => array:2 [ "nombre" => "Rosa" "apellidos" => "Coelho" ] 6 => array:2 [ "nombre" => "Guilherme" "apellidos" => "Macedo" ] 7 => array:2 [ "nombre" => "Maria Júlia" "apellidos" => "Maciel" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204914001718" "doi" => "10.1016/j.repce.2014.02.012" "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/S2174204914001718?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255114000717?idApp=UINPBA00004E" "url" => "/08702551/0000003300000009/v1_201410010215/S0870255114000717/v1_201410010215/pt/main.assets" ] "asociados" => array:1 [ 0 => array:20 [ "pii" => "S087025511500075X" "issn" => "08702551" "doi" => "10.1016/j.repc.2015.01.008" "estado" => "S300" "fechaPublicacion" => "2015-04-01" "aid" => "625" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Rev Port Cardiol. 2015;34:299-300" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2767 "formatos" => array:3 [ "EPUB" => 164 "HTML" => 2018 "PDF" => 585 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Noncompaction in Fabry's disease" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "299" "paginaFinal" => "300" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Não compactação na doença de Fabry" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Josef Finsterer, Sinda Zarrouk-Mahjoub, Sonam Kothari" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Josef" "apellidos" => "Finsterer" ] 1 => array:2 [ "nombre" => "Sinda" "apellidos" => "Zarrouk-Mahjoub" ] 2 => array:2 [ "nombre" => "Sonam" "apellidos" => "Kothari" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204915000926" "doi" => "10.1016/j.repce.2015.04.004" "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/S2174204915000926?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S087025511500075X?idApp=UINPBA00004E" "url" => "/08702551/0000003400000004/v2_201504180206/S087025511500075X/v2_201504180206/en/main.assets" ] ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case report</span>" "titulo" => "Histopathological evidence of Fabry disease in a female patient with left ventricular noncompaction" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "565.e1" "paginaFinal" => "565.e6" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Elisabete Martins, Teresa Pinho, Stirling Carpenter, Sérgio Leite, Raquel Garcia, António Madureira, João Paulo Oliveira" "autores" => array:7 [ 0 => array:4 [ "nombre" => "Elisabete" "apellidos" => "Martins" "email" => array:1 [ 0 => "elismartins@med.up.pt" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Teresa" "apellidos" => "Pinho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Stirling" "apellidos" => "Carpenter" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Sérgio" "apellidos" => "Leite" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Raquel" "apellidos" => "Garcia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "António" "apellidos" => "Madureira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0025" ] ] ] 6 => array:3 [ "nombre" => "João Paulo" "apellidos" => "Oliveira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Medical School of Porto, Department of Medicine, São João University Hospital, Porto, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Cardiology Department, São João University Hospital, Porto, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Pathology Department, São João University Hospital, Porto, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Radiology Department, São João University Hospital, Porto, Portugal" "etiqueta" => "d" "identificador" => "aff0025" ] 4 => array:3 [ "entidad" => "Medical School of Porto, Genetics Department, São João University Hospital, Porto, Portugal" "etiqueta" => "e" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Evidência histopatológica de doença de Fabry numa doente com não compactação do ventrículo esquerdo" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 646 "Ancho" => 995 "Tamanyo" => 132034 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">On electron microscopy the dark granules are made up of concentric laminae, clearly visible where they run perpendicular to the cut (asterisk).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the alpha-galactosidase gene (<span class="elsevierStyleItalic">GLA</span>). Partial or complete deficiency of alpha-galactosidase enzyme activity leads to progressive intracellular accumulation of neutral glycosphingolipids containing terminal alpha-D-galactosyl residues, especially of globotriaosylceramide (Gb3), in many different cell types and tissues.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> The multisystemic manifestations of the classical phenotype of Fabry disease, which is typically observed in males with absent or extremely low alpha-galactosidase activity,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> include acroparesthesias and other neuropathic symptoms, angiokeratomas, hypohidrosis, gastrointestinal problems and cornea verticillata, usually beginning in childhood or adolescence, and later-onset major kidney, cardiac and cerebrovascular complications.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–4</span></a> Deacylated globotriaosylceramide, globotriaosylsphingosine (lysoGb3) may be an important pathogenic mediator involved in the onset and progression of some of the clinical and pathological manifestations of Fabry disease.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Accumulation of Gb3 may occur in all the cellular components of the heart,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> causing a variety of clinical manifestations, including left ventricular hypertrophy (LVH), valvular disease (especially mitral regurgitation), myocardial ischemia, and arrhythmias.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The most frequent cardiac presentation of Fabry disease is a cardiomyopathy characterized by progressive, usually concentric, LVH and replacement fibrosis with preferential localization in the basal posterolateral left ventricular (LV) wall segments.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Heart disease in affected females tends to be clinically recognized later than in males, usually after the fourth decade of life.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,7,8</span></a> Cardiac complications are the most frequently reported cause of death in females with Fabry disease.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Abnormalities of tissue Doppler mitral annulus velocities can be observed in patients with normal thickness of the cardiac wall, representing an early sign of myocardial damage.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Other echocardiographic findings have been associated with Fabry disease, although none is pathognomonic. The appearance of a binary endocardial appearance,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> prominent papillary muscles or right ventricular involvement may also be encountered in ventricular hypertrophy secondary to other etiologies.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a> There are fewer data regarding the association between LV noncompaction (LVNC) and Fabry disease.</p><p id="par0025" class="elsevierStylePara elsevierViewall">We report a diagnosis of LVNC by cardiac magnetic resonance imaging (CMRI) in a young woman with histologically confirmed Fabry disease cardiomyopathy.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0030" class="elsevierStylePara elsevierViewall">A 30-year-old woman, heterozygous for a nonsense <span class="elsevierStyleItalic">GLA</span> mutation (p.R220X) associated with the classical phenotype of Fabry disease, was referred to the cardiology clinic for routine screening of cardiovascular manifestations of the disease. The assay of alpha-galactosidase in leukocytes had revealed a mild deficiency of enzymatic activity (25 nmol/h/mg; normal range: 36-80), as typically observed in heterozygotes.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The patient was asymptomatic and did not manifest any other typical signs of the disease except for cornea verticillata on slit lamp ophthalmological examination, and two small angiokeratomas, on the face and in the right inframammary region. Her blood pressure, chest examination and heart and lung auscultation were normal.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Renal function was normal, with plasma creatinine level of 0.65 mg/dl and urinary albumin/creatinine ratio of 4.8 mg/g. Plasma lysoGb concentration was 7.45 nmol (normal range: 0-2.2), and the urinary excretion of Gb3 and lysoGb3 were, respectively, 36 μg/mmol of creatinine (normal range: 0-25) and 67 pmol/mmol of creatinine (normal range: undetectable).</p><p id="par0045" class="elsevierStylePara elsevierViewall">The ECG revealed sinus bradycardia, without criteria of LVH or a short PR interval (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). The 24-hour Holter study revealed no rhythm abnormalities. The echocardiogram showed normal-sized chambers and normal basal and mid LV wall thickness. Systolic and diastolic functional parameters were within normal limits, including systolic (Sa), early diastolic (Ea), and late diastolic (Aa) tissue Doppler velocities at the mitral valve annulus. The 4-chamber apical view suggested the presence of hypertrabeculation of the apical segments of the LV, but without clear criteria of noncompaction due to insufficient acoustic window quality. For this reason CMRI was performed.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The CMRI revealed marked trabeculation in the apical segments of the LV with a diastolic ratio of noncompacted/compacted layers of 2.6, fulfilling CMRI criteria for noncompaction (<a class="elsevierStyleCrossRefs" href="#fig0010">Figures 2–4</a>). LV mass was within normal limits and no delayed enhancement suggestive of fibrosis was detected after gadolinium administration.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">To further investigate the relationship between this morphological finding and Fabry cardiomyopathy in a female with Fabry disease and no other evidence of cardiac involvement, a transjugular endomyocardial biopsy was obtained. Histopathological examination of myocardial fragments from the right ventricle showed marked deposition of glycosphingolipids in cardiomyocytes, sparing the endothelial cells (<a class="elsevierStyleCrossRefs" href="#fig0025">Figures 5 and 6</a>). Based on this finding, the patient was proposed for enzyme replacement therapy.</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">LVNC is a focal myocardial disorder characterized by a two-layered structure in which a noncompacted layer with numerous prominent trabeculations and deep intertrabecular recesses overlaps a thinner compacted epicardial layer.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> This morphological abnormality has been attributed to an embryonic arrest of the myocardial morphogenesis process, possibly due to abnormal regulation of cardiomyocyte polarization and myofibrillogenesis,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> but “late-onset” variants and even “reverse remodeling” of the ventricular noncompaction pattern have also been described, supporting the hypothesis that it could also just be a morphological variant of other cardiomyopathies.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15–17</span></a> Given the considerable controversy surrounding its pathogenesis, diagnosis and management, the European Working Group of Myocardial Diseases considers LVNC as an unclassified form of cardiomyopathy.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The genetic basis is heterogeneous and isolated LVNC has been described in association with various hereditary disorders, mostly due to cardiac sarcomeric protein mutations,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> but also in some myopathies and metabolic diseases.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,20–22</span></a> Reports of an association between Fabry disease and LVNC are scarce. Azevedo et al. recently described the finding of an LVNC pattern in a 32-year-old woman,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> heterozygous for the <span class="elsevierStyleItalic">GLA</span> mutation p.F113L, which was originally reported in association with a late-onset cardiac phenotype, with preservation of some residual enzyme activity.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> However, as these authors provided no other evidence of Fabry cardiomyopathy in their case, their suggestion that LVNC might be a rare cardiac manifestation of Fabry disease was based solely on the improbability of the patient having two rare, unrelated cardiac diseases.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> It is noteworthy that Stöllberger et al. had emphasized the importance of endomyocardial biopsy to conclusively establish an association of Fabry disease with LV hypertrabeculation/noncompaction.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Unlike the referenced case the diagnosis of Fabry cardiomyopathy in our patient was unequivocally demonstrated by histopathological criteria. However, due to the patchy cardiac involvement expected from random X-chromosome inactivation in females heterozygous for X-linked diseases,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> it is not possible to conclude definitely that the noncompaction pattern arose in an alpha-galactosidase deficient region of the LV myocardium.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In patients with Fabry disease, irrespective of their gender, contraction and relaxation tissue Doppler mitral annulus velocities are inversely related to LV mass, but may be already significantly reduced prior to development of LVH,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> constituting an early marker of disease progression.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> The normal tissue Doppler parameters in our patient strongly suggest that Fabry cardiomyopathy was diagnosed at an early stage, still without significant disturbance of myocardial performance. Common to our patient and to the patient previously reported is the diagnosis of LVNC in young adult females with Fabry disease, at an early stage in the natural history of Fabry cardiomyopathy. As LVNC is a very unusual finding in Fabry disease,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> the remarkable similarities between the two cases are unlikely to be merely fortuitous.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The plasma of patients with Fabry disease contains a substance – possibly lysoGb3<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> – that stimulates proliferation of cardiomyocytes in vitro.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> In addition, studies in isolated cardiomyocytes of patients with Fabry disease have shown that Gb3 accumulation leads to degradation of myofilament proteins and to a dysfunctional state characterized by abnormally high resting tension and abnormally low active tension.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">On the other hand, a number of molecular mechanisms have been described in animal models that might contribute to the development of myocardial hypertrabeculation/noncompaction.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,31</span></a> Among these, the development of noncompaction without an increase in cell proliferative activity in trabecular LV myocardium, and the role of impaired myofibrillogenesis in the pathogenesis of noncompacted myocardium, may be particularly helpful in understanding the development of LVNC in adult patients with Fabry disease.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Taking into consideration (i) the foregoing human and animal experimental data, (ii) the rarity of LVNC in patients with Fabry disease, and (iii) the appearance, disappearance or changing morphological pattern of LVNC that have been described in several cases,<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> it can be hypothesised that Fabry disease is a risk factor for myocardial noncompaction (possibly related to myofibrillolysis in cardiomyocytes) that would fully manifest only in patients carrying additional genetic or other risk factors for its development. Furthermore, expression of LVNC in Fabry disease might occur transiently and at an early stage in the natural history of Fabry cardiomyopathy. Long-term follow-up of affected patients will help to elucidate these issues.</p><p id="par0095" class="elsevierStylePara elsevierViewall">As conclusions, our case illustrates the important role of endomyocardial biopsy in the clarification of doubtful or atypical findings related to cardiac Fabry disease, even in heterozygous women, and corroborates the contention that Fabry disease should be included in the differential diagnosis of LV hypertrabeculation/noncompaction.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ethical disclosures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Protection of human and animal subjects</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Confidentiality of data</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Right to privacy and informed consent</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres373504" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec352604" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres373505" "titulo" => "Resumo" ] 3 => array:2 [ "identificador" => "xpalclavsec352603" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-02-13" "fechaAceptado" => "2014-08-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec352604" "palabras" => array:3 [ 0 => "Fabry disease" 1 => "Hypertrabeculation/noncompaction" 2 => "Endomyocardial biopsy" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec352603" "palabras" => array:3 [ 0 => "Doença de Fabry" 1 => "Hipertrabeculação/não compactação" 2 => "Biópsia endomiocárdica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the alpha-galactosidase gene. The most frequent cardiac presentation of Fabry disease is cardiomyopathy characterized by left ventricular (LV) hypertrophy, usually concentric.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Heart disease in affected females tends to be clinically recognized later than in males and cardiac complications are the most frequently reported cause of death in females with Fabry disease. There are few data regarding the association between Fabry disease and LV noncompaction. We report a case of a 30-year-old asymptomatic woman, heterozygous for a nonsense alpha-galactosidase gene mutation (p.R220X), who presented LV noncompaction on cardiac magnetic resonance imaging, without LV wall hypertrophy. Histopathological examination of myocardial fragments showed marked deposition of glycosphingolipids in cardiomyocytes, confirming the diagnosis of Fabry cardiomyopathy. Based on this finding, the patient was proposed for enzyme replacement therapy. This case illustrates the role of endomyocardial biopsy in the clarification of doubtful or atypical findings related to cardiac Fabry disease, even in heterozygous women, and corroborates the contention that Fabry disease should be included in the differential diagnosis of LV hypertrabeculation/noncompaction.</p>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A doença de Fabry é uma doença rara de armazenamento lisossómico, ligada ao cromossoma X, causada por mutações no gene da α – galactosidase. A apresentação cardíaca mais frequente é uma miocardiopatia caracterizada por hipertrofia ventricular esquerda geralmente concêntrica.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Nas mulheres afetadas a doença cardíaca tende a ser clinicamente reconhecida mais tardiamente do que em homens e as complicações cardíacas são a causa mais frequente de morte reportada em mulheres com doença de Fabry. Existem poucos dados sobre a associação entre a doença de Fabry e a não compactação do ventrículo esquerdo (VE). Reportamos o caso de uma mulher assintomática, com 30 anos de idade, heterozigota para uma mutação nonsense do gene da α–galactosidase gene (p.R220X) que apresentava critérios de VE não compactado na ressonância magnética cardíaca, sem hipertrofia das restantes paredes ventriculares. O exame histopatológico de fragmentos do miocárdio mostrou deposição acentuada de glicoesfingolípidos nos cardiomiócitos, corroborando o diagnóstico de miocardiopatia de Fabry. Com base nestes achados, foi proposto o início de terapia de substituição enzimática. Este caso ilustra o papel da biópsia endomiocárdica no esclarecimento de achados duvidosos ou atípicos relacionados com a doença de Fabry cardíaca, mesmo em mulheres heterozigotas, e corrobora a afirmação de que a doença de Fabry deve ser incluída no diagnóstico diferencial da hipertrabeculação/não compactação do VE.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1373 "Ancho" => 2668 "Tamanyo" => 761275 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Resting ECG showing sinus bradycardia.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1287 "Ancho" => 1300 "Tamanyo" => 137001 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Left ventricular vertical (A) and horizontal (B) long-axis cine steady-state free precession magnetic resonance images at (a) end-diastole and (b) end-systole demonstrating normal ventricular systolic function and hypertrabeculation of left ventricular apical segments.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 487 "Ancho" => 1500 "Tamanyo" => 60558 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Short-axis cine steady-state free precession magnetic resonance images at basal, mid-ventricular and apical levels, confirming apical hypertrabeculation and papillary muscle disarray.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1014 "Ancho" => 1400 "Tamanyo" => 175764 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">(A and B) Cardiac magnetic resonance late gadolinium images revealing no myocardial delayed enhancement.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 796 "Ancho" => 996 "Tamanyo" => 178361 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">In this microscopic field from a semithin section of glutaraldehyde-fixed, epoxy resin-embedded tissue stained with toluidine blue, the majority of cardiac muscle fibers contain dark granular accumulations in their center.</p>" ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 646 "Ancho" => 995 "Tamanyo" => 132034 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">On electron microscopy the dark granules are made up of concentric laminae, clearly visible where they run perpendicular to the cut (asterisk).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:32 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The molecular defect leading to Fabry disease: structure of human alpha-galactosidase" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.C. Garman" 1 => "D.N. Garboczi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jmb.2004.01.035" "Revista" => array:6 [ "tituloSerie" => "J Mol Biol" "fecha" => "2004" "volumen" => "337" "paginaInicial" => "319" "paginaFinal" => "335" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15003450" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Narrative review: Fabry disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.T. Clarke" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2007" "volumen" => "146" "paginaInicial" => "425" "paginaFinal" => "433" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17371887" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R.J. Desnick" 1 => "R. Brady" 2 => "J. Barranger" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2003" "volumen" => "138" "paginaInicial" => "338" "paginaFinal" => "346" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12585833" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fabry's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Y.A. Zarate" 1 => "R.J. Hopkin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(08)61589-5" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2008" "volumen" => "372" "paginaInicial" => "1427" "paginaFinal" => "1435" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18940466" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Elevated globotriaosylsphingosine is a hallmark of Fabry disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.M. Aerts" 1 => "J.E. Groener" 2 => "S. Kuiper" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.0712309105" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci U S A" "fecha" => "2008" "volumen" => "105" "paginaInicial" => "2812" "paginaFinal" => "2817" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18287059" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "When should cardiologists suspect Anderson-Fabry disease?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "F.I. Gambarin" 1 => "E. Disabella" 2 => "J. Narula" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.amjcard.2010.07.016" "Revista" => array:6 [ "tituloSerie" => "Am J Cardiol" "fecha" => "2010" "volumen" => "106" "paginaInicial" => "1492" "paginaFinal" => "1499" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21059442" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Linhart" 1 => "C. Kampmann" 2 => "J.L. Zamorano" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehm153" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2007" "volumen" => "28" "paginaInicial" => "1228" "paginaFinal" => "1235" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17483538" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "W.R. Wilcox" 1 => "J.P. Oliveira" 2 => "R.J. Hopkin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ymgme.2007.09.013" "Revista" => array:6 [ "tituloSerie" => "Mol Genet Metab" "fecha" => "2008" "volumen" => "93" "paginaInicial" => "112" "paginaFinal" => "128" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18037317" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tissue Doppler imaging in Fabry disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. Pieroni" 1 => "C. Chimenti" 2 => "A. Russo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Curr Opin Cardiol" "fecha" => "2004" "volumen" => "19" "paginaInicial" => "452" "paginaFinal" => "457" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15316452" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The binary endocardial appearance is a poor discriminator of Anderson-Fabry disease from familial hypertrophic cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Kounas" 1 => "C. Demetrescu" 2 => "A.A. Pantazis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2008.02.046" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2008" "volumen" => "51" "paginaInicial" => "2058" "paginaFinal" => "2061" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18498962" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Fabry cardiomyopathy: models for the cardiologist" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "F. Weidemann" 1 => "M. Niemann" 2 => "D.G. Warnock" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev-med-090910-085119" "Revista" => array:6 [ "tituloSerie" => "Annu Rev Med" "fecha" => "2011" "volumen" => "62" "paginaInicial" => "59" "paginaFinal" => "67" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21090963" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Right ventricular involvement in Fabry disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "T. Palecek" 1 => "G. Dostalova" 2 => "P. Kuchynka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.echo.2008.09.002" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Echocardiogr" "fecha" => "2008" "volumen" => "21" "paginaInicial" => "1265" "paginaFinal" => "1268" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18835697" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Isolated noncompaction of left ventricular myocardium. A study of eight cases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "T.K. Chin" 1 => "J.K. Perloff" 2 => "R.G. Williams" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "1990" "volumen" => "82" "paginaInicial" => "507" "paginaFinal" => "513" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2372897" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular mechanism of ventricular trabeculation/compaction and the pathogenesis of the left ventricular noncompaction cardiomyopathy (LVNC)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "W. Zhang" 1 => "H. Chen" 2 => "X. Qu" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Med Genet C Semin Med Genet" "fecha" => "2013" "volumen" => "163" "paginaInicial" => "144" "paginaFinal" => "156" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of cardiac resynchronisation therapy on dilated cardiomyopathy with isolated ventricular non-compaction" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. Bertini" 1 => "M. Ziacchi" 2 => "M. Biffi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/hrt.2010.211607" "Revista" => array:6 [ "tituloSerie" => "Heart" "fecha" => "2011" "volumen" => "97" "paginaInicial" => "295" "paginaFinal" => "300" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21163889" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acquired noncompaction associated with coronary heart disease and myopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Finsterer" 1 => "C. Stollberger" 2 => "E. Bonner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.hrtlng.2009.09.001" "Revista" => array:6 [ "tituloSerie" => "Heart Lung" "fecha" => "2010" "volumen" => "39" "paginaInicial" => "240" "paginaFinal" => "241" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20457346" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Left ventricular hypertrabeculation/noncompaction" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Stollberger" 1 => "J. Finsterer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0894-7317(03)00514-5" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Echocardiogr" "fecha" => "2004" "volumen" => "17" "paginaInicial" => "91" "paginaFinal" => "100" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14712196" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases" "autores" => array:1 [ 0 => array:2 [ "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:6 [ "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" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in sarcomere protein genes in left ventricular noncompaction" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Klaassen" 1 => "S. Probst" 2 => "E. Oechslin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.107.746164" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2008" "volumen" => "117" "paginaInicial" => "2893" "paginaFinal" => "2901" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18506004" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Noncompaction of the ventricular myocardium" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "B.C. Weiford" 1 => "V.D. Subbarao" 2 => "K.M. Mulhern" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/01.CIR.0000132478.60674.D0" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2004" "volumen" => "109" "paginaInicial" => "2965" "paginaFinal" => "2971" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15210614" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Noncompaction of the ventricular myocardium" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Y. Agmon" 1 => "H.M. Connolly" 2 => "L.J. Olson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Am Soc Echocardiogr" "fecha" => "1999" "volumen" => "12" "paginaInicial" => "859" "paginaFinal" => "863" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10511656" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Noncompaction myocardium in association with type Ib glycogen storage disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "B. Goeppert" 1 => "M. Lindner" 2 => "M.N. Vogel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.prp.2012.06.007" "Revista" => array:6 [ "tituloSerie" => "Pathol Res Pract" "fecha" => "2012" "volumen" => "208" "paginaInicial" => "620" "paginaFinal" => "622" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22854198" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Left ventricular noncompaction in a patient with fabry disease: overdiagnosis, morphological manifestation of fabry disease or two unrelated rare conditions in the same patient?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "O. Azevedo" 1 => "P. Gaspar" 2 => "C. Sa Miranda" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000330924" "Revista" => array:6 [ "tituloSerie" => "Cardiology" "fecha" => "2011" "volumen" => "119" "paginaInicial" => "155" "paginaFinal" => "159" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21952291" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fabry disease: thirty-five mutations in the alpha-galactosidase A gene in patients with classic and variant phenotypes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C.M. Eng" 1 => "G.A. Ashley" 2 => "T.S. Burgert" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mol Med" "fecha" => "1997" "volumen" => "3" "paginaInicial" => "174" "paginaFinal" => "182" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9100224" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is left ventricular hypertrabeculation/noncompaction a cardiac manifestation of Fabry's disease?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. Stollberger" 1 => "J. Finsterer" 2 => "T. Voigtlander" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00392-003-1018-0" "Revista" => array:6 [ "tituloSerie" => "Z Kardiol" "fecha" => "2003" "volumen" => "92" "paginaInicial" => "966" "paginaFinal" => "969" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14634768" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "X-chromosome inactivation and human genetic disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.F. Lyon" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Acta Paediatr Suppl" "fecha" => "2002" "volumen" => "91" "paginaInicial" => "107" "paginaFinal" => "112" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12572852" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early detection of Fabry cardiomyopathy by tissue Doppler imaging" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. Pieroni" 1 => "C. Chimenti" 2 => "R. Ricci" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/01.CIR.0000061952.27445.A0" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2003" "volumen" => "107" "paginaInicial" => "1978" "paginaFinal" => "1984" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12668521" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Usefulness of tissue Doppler on early detection of cardiac disease in Fabry patients and potential role of enzyme replacement therapy (ERT) for avoiding progression of disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J. Zamorano" 1 => "V. Serra" 2 => "L. Perez de Isla" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ejechocard/jer109" "Revista" => array:6 [ "tituloSerie" => "Eur J Echocardiogr" "fecha" => "2011" "volumen" => "12" "paginaInicial" => "671" "paginaFinal" => "677" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21810826" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac and vascular hypertrophy in Fabry disease: evidence for a new mechanism independent of blood pressure and glycosphingolipid deposition" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "F. Barbey" 1 => "N. Brakch" 2 => "A. Linhart" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/01.ATV.0000209649.60409.38" "Revista" => array:6 [ "tituloSerie" => "Arterioscler Thromb Vasc Biol" "fecha" => "2006" "volumen" => "26" "paginaInicial" => "839" "paginaFinal" => "844" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16469946" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Myofilament degradation and dysfunction of human cardiomyocytes in Fabry disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. Chimenti" 1 => "N. Hamdani" 2 => "N.M. Boontje" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2353/ajpath.2008.070576" "Revista" => array:6 [ "tituloSerie" => "Am J Pathol" "fecha" => "2008" "volumen" => "172" "paginaInicial" => "1482" "paginaFinal" => "1490" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18467700" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of ventricular hypertrabeculation and noncompaction using genetically engineered mouse models" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "H. Chen" 1 => "W. Zhang" 2 => "D. Li" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00246-009-9406-5" "Revista" => array:6 [ "tituloSerie" => "Pediatr Cardiol" "fecha" => "2009" "volumen" => "30" "paginaInicial" => "626" "paginaFinal" => "634" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19396388" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Disappearance of left ventricular hypertrabeculation/noncompaction after biventricular pacing in a patient with polyneuropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. Stollberger" 1 => "H. Keller" 2 => "J. Finsterer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cardfail.2006.11.007" "Revista" => array:6 [ "tituloSerie" => "J Card Fail" "fecha" => "2007" "volumen" => "13" "paginaInicial" => "211" "paginaFinal" => "214" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17448419" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/08702551/0000003300000009/v1_201410010215/S0870255114001851/v1_201410010215/en/main.assets" "Apartado" => array:4 [ "identificador" => "362" "tipo" => "SECCION" "pt" => array:2 [ "titulo" => "Casos clínicos" "idiomaDefecto" => true ] "idiomaDefecto" => "pt" ] "PDF" => "https://static.elsevier.es/multimedia/08702551/0000003300000009/v1_201410010215/S0870255114001851/v1_201410010215/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255114001851?idApp=UINPBA00004E" ]
| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 7 | 9 | 16 |
| 2024 Outubro | 42 | 46 | 88 |
| 2024 Setembro | 68 | 34 | 102 |
| 2024 Agosto | 62 | 28 | 90 |
| 2024 Julho | 50 | 40 | 90 |
| 2024 Junho | 54 | 30 | 84 |
| 2024 Maio | 65 | 26 | 91 |
| 2024 Abril | 52 | 28 | 80 |
| 2024 Maro | 49 | 22 | 71 |
| 2024 Fevereiro | 48 | 30 | 78 |
| 2024 Janeiro | 31 | 24 | 55 |
| 2023 Dezembro | 40 | 33 | 73 |
| 2023 Novembro | 57 | 39 | 96 |
| 2023 Outubro | 38 | 17 | 55 |
| 2023 Setembro | 19 | 19 | 38 |
| 2023 Agosto | 25 | 19 | 44 |
| 2023 Julho | 36 | 11 | 47 |
| 2023 Junho | 45 | 17 | 62 |
| 2023 Maio | 60 | 27 | 87 |
| 2023 Abril | 40 | 3 | 43 |
| 2023 Maro | 57 | 24 | 81 |
| 2023 Fevereiro | 53 | 19 | 72 |
| 2023 Janeiro | 48 | 16 | 64 |
| 2022 Dezembro | 64 | 20 | 84 |
| 2022 Novembro | 60 | 30 | 90 |
| 2022 Outubro | 62 | 20 | 82 |
| 2022 Setembro | 56 | 32 | 88 |
| 2022 Agosto | 62 | 34 | 96 |
| 2022 Julho | 74 | 36 | 110 |
| 2022 Junho | 42 | 29 | 71 |
| 2022 Maio | 61 | 27 | 88 |
| 2022 Abril | 68 | 30 | 98 |
| 2022 Maro | 71 | 46 | 117 |
| 2022 Fevereiro | 56 | 36 | 92 |
| 2022 Janeiro | 60 | 25 | 85 |
| 2021 Dezembro | 43 | 27 | 70 |
| 2021 Novembro | 51 | 37 | 88 |
| 2021 Outubro | 47 | 34 | 81 |
| 2021 Setembro | 49 | 40 | 89 |
| 2021 Agosto | 36 | 29 | 65 |
| 2021 Julho | 30 | 35 | 65 |
| 2021 Junho | 23 | 19 | 42 |
| 2021 Maio | 24 | 24 | 48 |
| 2021 Abril | 58 | 25 | 83 |
| 2021 Maro | 62 | 25 | 87 |
| 2021 Fevereiro | 69 | 15 | 84 |
| 2021 Janeiro | 45 | 12 | 57 |
| 2020 Dezembro | 32 | 8 | 40 |
| 2020 Novembro | 64 | 13 | 77 |
| 2020 Outubro | 25 | 21 | 46 |
| 2020 Setembro | 58 | 8 | 66 |
| 2020 Agosto | 23 | 7 | 30 |
| 2020 Julho | 61 | 8 | 69 |
| 2020 Junho | 53 | 5 | 58 |
| 2020 Maio | 57 | 12 | 69 |
| 2020 Abril | 51 | 11 | 62 |
| 2020 Maro | 59 | 4 | 63 |
| 2020 Fevereiro | 140 | 18 | 158 |
| 2020 Janeiro | 39 | 10 | 49 |
| 2019 Dezembro | 54 | 5 | 59 |
| 2019 Novembro | 38 | 8 | 46 |
| 2019 Outubro | 319 | 6 | 325 |
| 2019 Setembro | 70 | 8 | 78 |
| 2019 Agosto | 48 | 12 | 60 |
| 2019 Julho | 55 | 15 | 70 |
| 2019 Junho | 35 | 15 | 50 |
| 2019 Maio | 68 | 19 | 87 |
| 2019 Abril | 38 | 10 | 48 |
| 2019 Maro | 109 | 10 | 119 |
| 2019 Fevereiro | 88 | 10 | 98 |
| 2019 Janeiro | 61 | 9 | 70 |
| 2018 Dezembro | 76 | 11 | 87 |
| 2018 Novembro | 170 | 12 | 182 |
| 2018 Outubro | 330 | 26 | 356 |
| 2018 Setembro | 48 | 8 | 56 |
| 2018 Agosto | 64 | 10 | 74 |
| 2018 Julho | 33 | 9 | 42 |
| 2018 Junho | 69 | 7 | 76 |
| 2018 Maio | 74 | 9 | 83 |
| 2018 Abril | 105 | 6 | 111 |
| 2018 Maro | 59 | 9 | 68 |
| 2018 Fevereiro | 35 | 11 | 46 |
| 2018 Janeiro | 36 | 5 | 41 |
| 2017 Dezembro | 82 | 11 | 93 |
| 2017 Novembro | 49 | 9 | 58 |
| 2017 Outubro | 54 | 17 | 71 |
| 2017 Setembro | 57 | 8 | 65 |
| 2017 Agosto | 52 | 12 | 64 |
| 2017 Julho | 39 | 9 | 48 |
| 2017 Junho | 47 | 14 | 61 |
| 2017 Maio | 44 | 17 | 61 |
| 2017 Abril | 30 | 21 | 51 |
| 2017 Maro | 33 | 8 | 41 |
| 2017 Fevereiro | 75 | 3 | 78 |
| 2017 Janeiro | 28 | 4 | 32 |
| 2016 Dezembro | 21 | 9 | 30 |
| 2016 Novembro | 28 | 7 | 35 |
| 2016 Outubro | 33 | 9 | 42 |
| 2016 Setembro | 49 | 5 | 54 |
| 2016 Agosto | 33 | 1 | 34 |
| 2016 Julho | 8 | 10 | 18 |
| 2016 Junho | 5 | 10 | 15 |
| 2016 Maio | 29 | 5 | 34 |
| 2016 Abril | 42 | 3 | 45 |
| 2016 Maro | 69 | 9 | 78 |
| 2016 Fevereiro | 75 | 26 | 101 |
| 2016 Janeiro | 61 | 9 | 70 |
| 2015 Dezembro | 63 | 9 | 72 |
| 2015 Novembro | 46 | 7 | 53 |
| 2015 Outubro | 56 | 10 | 66 |
| 2015 Setembro | 46 | 16 | 62 |
| 2015 Agosto | 58 | 6 | 64 |
| 2015 Julho | 58 | 5 | 63 |
| 2015 Junho | 48 | 6 | 54 |
| 2015 Maio | 50 | 5 | 55 |
| 2015 Abril | 41 | 11 | 52 |
| 2015 Maro | 40 | 5 | 45 |
| 2015 Fevereiro | 55 | 7 | 62 |
| 2015 Janeiro | 36 | 9 | 45 |
| 2014 Dezembro | 55 | 15 | 70 |
| 2014 Novembro | 62 | 21 | 83 |
| 2014 Outubro | 156 | 102 | 258 |
Mostrar tudo
