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um m&#233;todo n&#227;o invasivo para quantifica&#231;&#227;o da inerva&#231;&#227;o simp&#225;tica card&#237;aca&#46; Estudos pr&#233;vios demonstraram que a inerva&#231;&#227;o simp&#225;tica mioc&#225;rdica detetada nas imagens com MIBG&#8208;I<span class="elsevierStyleSup">123</span> est&#225; diminu&#237;da numa fase inicial da doen&#231;a<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">4&#44;5</span></a> e que a redu&#231;&#227;o do &#237;ndice de capta&#231;&#227;o cora&#231;&#227;o&#47;mediastino &#40;C&#47;M&#41; tardio de MIBG&#8208;I<span class="elsevierStyleSup">123</span> &#233; um valioso preditor progn&#243;stico&#44; associando&#8208;se fortemente ao risco de mortalidade a longo prazo<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a>&#46; No entanto&#44; a progress&#227;o da desnerva&#231;&#227;o card&#237;aca durante a evolu&#231;&#227;o da PAF TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M nunca foi caracterizada em cintigrafias seriadas com MIBG&#8208;I<span class="elsevierStyleSup">123</span>&#44; e o eventual valor acrescido de avalia&#231;&#245;es repetidas do &#237;ndice C&#47;M tardio para fins de estratifica&#231;&#227;o de progn&#243;stico permanece desconhecido&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">O transplante hep&#225;tico tem sido amplamente usado para atenuar a progress&#227;o da PAF e at&#233; recentemente era a &#250;nica op&#231;&#227;o terap&#234;utica para estes doentes<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a>&#46; O transplante hep&#225;tico interrompe a progress&#227;o do compromisso neurol&#243;gico e melhora a sobreviv&#234;ncia&#44; especialmente se for realizado nas fases iniciais da doen&#231;a sintom&#225;tica<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a>&#46; Em contrapartida&#44; a amiloidose card&#237;aca pode continuar a progredir ap&#243;s o transplante hep&#225;tico&#44; levando a espessamento progressivo do mioc&#225;rdio&#44; arritmias e defeitos da condu&#231;&#227;o card&#237;aca<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">8&#8211;13</span></a>&#46; No entanto&#44; pouco se sabe sobre a evolu&#231;&#227;o da desnerva&#231;&#227;o card&#237;aca ap&#243;s o transplante hep&#225;tico&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Deste modo&#44; o nosso objetivo foi avaliar o impacto do transplante hep&#225;tico na progress&#227;o da desnerva&#231;&#227;o card&#237;aca em doentes com PAF TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">M&#233;todos</span><p id="par0025" class="elsevierStylePara elsevierViewall">Realizou&#8208;se um estudo observacional prospetivo de indiv&#237;duos consecutivos portadores da muta&#231;&#227;o TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M&#46; Todos os doentes foram submetidos a avalia&#231;&#227;o cardiol&#243;gica anual e procedeu&#8208;se periodicamente a determina&#231;&#227;o do &#237;ndice de capta&#231;&#227;o C&#47;M de MIBG&#8208;I<span class="elsevierStyleSup">123</span>&#46; A progress&#227;o da desnerva&#231;&#227;o card&#237;aca foi avaliada pela compara&#231;&#227;o dos &#237;ndices de capta&#231;&#227;o C&#47;M em exames sucessivos&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Cintigrafia com MIBG&#8208;I</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">123</span></span><span class="elsevierStyleItalic">&#46;</span> A cintigrafia foi realizada ap&#243;s pr&#233; medica&#231;&#227;o com uma solu&#231;&#227;o de iodeto de pot&#225;ssio &#40;solu&#231;&#227;o de Lugol&#41; para bloquear a absor&#231;&#227;o de <span class="elsevierStyleSmallCaps">I</span><span class="elsevierStyleSup">123</span> livre pela gl&#226;ndula tiroide&#46; N&#227;o se suspendeu qualquer terap&#234;utica cr&#243;nica previamente &#224; realiza&#231;&#227;o do exame&#46; Adquiriram&#8208;se imagens planares tor&#225;cicas anteriores&#44; 15 minutos &#40;imagem precoce&#41; e tr&#234;s horas &#40;imagem tardia&#41; ap&#243;s a inje&#231;&#227;o intravenosa de uma dose fixa de 185<span class="elsevierStyleHsp" style=""></span>MBq de MIBG&#8208;I<span class="elsevierStyleSup">123</span>&#46; As imagens foram realizadas utilizando um sistema com uma c&#226;mara de duas cabe&#231;as &#40;<span class="elsevierStyleItalic">Millenium&#44; General Electric Healthcare</span>&#41; equipado com um colimador de orif&#237;cios paralelos&#44; baixa energia e alta resolu&#231;&#227;o&#46; Utilizou&#8208;se uma janela de energia de 20&#37; centrada sobre o fotopico de 159<span class="elsevierStyleHsp" style=""></span>keV do <span class="elsevierStyleSmallCaps">I</span><span class="elsevierStyleSup">123</span>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A capta&#231;&#227;o de MIBG&#8208;I<span class="elsevierStyleSup">123</span> foi quantificada atrav&#233;s do c&#225;lculo do &#237;ndice C&#47;M&#44; o qual foi determinado dividindo o n&#250;mero de contagens m&#233;dias&#47;<span class="elsevierStyleItalic">pixel</span> de uma regi&#227;o de interesse desenhada &#224; volta do cora&#231;&#227;o pelo n&#250;mero de contagens m&#233;dias&#47;<span class="elsevierStyleItalic">pixel</span> do mediastino&#44; sem corre&#231;&#227;o para a atividade de fundo&#46; O <span class="elsevierStyleItalic">washout rate</span> &#40;WR&#41; mioc&#225;rdico foi calculado como a percentagem de redu&#231;&#227;o das contagens mioc&#225;rdicas entre as imagens precoces e as tardias&#58; &#40;&#91;&#237;ndice C&#47;M precoce &#8211; C&#47;M tardio&#93;&#47;&#237;ndice C&#47;M precoce&#41;<span class="elsevierStyleHsp" style=""></span>x<span class="elsevierStyleHsp" style=""></span>100&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lise estat&#237;stica</span><p id="par0040" class="elsevierStylePara elsevierViewall">As vari&#225;veis cont&#237;nuas com distribui&#231;&#227;o normal foram expressas pela m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>desvio padr&#227;o e foram comparadas usando os testes t&#8208;Student&#47;ANOVA&#46; As vari&#225;veis cont&#237;nuas com distribui&#231;&#227;o n&#227;o&#8208;normal foram descritas pela mediana e distribui&#231;&#227;o interquartil &#40;DIQ&#41;&#44; e foram comparadas usando os testes de Mann&#8208;Whitney&#47;Kruskal&#8208;Wallis&#46; Os par&#226;metros do MIBG foram correlacionados com a idade&#44; dura&#231;&#227;o dos sintomas e tempo decorrido at&#233; e ap&#243;s o transplante hep&#225;tico&#44; utilizando&#8208;se o coeficiente de Pearson e a correla&#231;&#227;o de Spearman&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">O impacto progn&#243;stico dos par&#226;metros do MIBG na predi&#231;&#227;o de morte por qualquer causa durante o seguimento foi determinado usando&#8208;se an&#225;lises de regress&#227;o de Cox univariadas e multivariadas &#40;com ajustamento para a idade&#41;&#46; Para evitar enviesamento&#44; as an&#225;lises multivariadas foram realizadas aplicando&#8208;se m&#233;todos sequenciais condicionais&#44; em que foram removidos do modelo em cada etapa as vari&#225;veis n&#227;o significativas &#40;valor p para inclus&#227;o de vari&#225;vel de 0&#44;05 e para a remo&#231;&#227;o de 0&#44;10&#41;&#46; A precis&#227;o dos modelos de predi&#231;&#227;o de mortalidade foi avaliada pela &#225;rea sob a curva <span class="elsevierStyleItalic">receiver operator characteristic</span> &#40;ROC&#41;&#44; considerando diferentes dura&#231;&#245;es de seguimento&#46; As taxas cumulativas de eventos em fun&#231;&#227;o da distribui&#231;&#227;o por quartis do &#237;ndice C&#47;M tardio foram avaliadas utilizando o m&#233;todo de Kaplan&#8208;Meier e o teste <span class="elsevierStyleItalic">log&#8208;rank</span>&#46; A an&#225;lise estat&#237;stica foi realizada com o <span class="elsevierStyleItalic">software</span> SPSS vers&#227;o 21&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; Illinois&#41;&#44; considerando&#8208;se estatisticamente significativo um valor de p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Caracteriza&#231;&#227;o da popula&#231;&#227;o</span><p id="par0050" class="elsevierStylePara elsevierViewall">Entre setembro de 1998 e julho de 2015&#44; 305 portadores da muta&#231;&#227;o TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M foram submetidos a avalia&#231;&#227;o cardiovascular&#46; Foram exclu&#237;dos da presente an&#225;lise 73 doentes&#58; 45 porque n&#227;o realizaram cintigrafia com MIBG e 28 porque a primeira cintigrafia foi efetuada j&#225; ap&#243;s transplanta&#231;&#227;o hep&#225;tica&#46; A popula&#231;&#227;o final foi composta por 232 doentes&#44; com idade mediana de 40 &#40;DIQ&#58; 32&#8208;55&#41; anos&#44; 54&#44;7&#37; dos quais do sexo feminino &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>127&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Aquando da avalia&#231;&#227;o card&#237;aca inicial&#44; 144 doentes &#40;62&#44;1&#37;&#41; tinham compromisso neurol&#243;gico estabelecido&#44; correspondendo os restantes 88 &#40;37&#44;9&#37;&#41; indiv&#237;duos a portadores assintom&#225;ticos&#46; Dos doentes sintom&#225;ticos&#44; 99 tinham desenvolvido manifesta&#231;&#245;es cl&#237;nicas antes dos 50 anos de idade&#46; Nos restantes 45 doentes&#44; a apresenta&#231;&#227;o cl&#237;nica ocorreu ap&#243;s os 50 anos &#40;doen&#231;a de in&#237;cio tardio&#41;&#46; A idade m&#233;dia de in&#237;cio dos sintomas foi de 38 &#40;DIQ&#58; 31&#8208;54&#41; anos e a dura&#231;&#227;o m&#233;dia dos sintomas aquando da avalia&#231;&#227;o card&#237;aca inicial foi de dois &#40;DIQ&#58; 0&#8208;3&#41; anos&#46; Dezanove portadores de muta&#231;&#227;o patog&#233;nica permaneciam livres de sintomas apesar de terem mais de 50 anos&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Cintigrafia com MIBG&#8208;I<span class="elsevierStyleSup">123</span></span><p id="par0060" class="elsevierStylePara elsevierViewall">Aquando da primeira avalia&#231;&#227;o&#44; os valores m&#233;dios do &#237;ndice C&#47;M precoce e tardio foram&#44; respetivamente&#44; 1&#44;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;23 e 1&#44;83<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#44; e o valor mediano do <span class="elsevierStyleItalic">WR</span> foi de 2&#44;5 &#40;DIQ&#58; &#8208;2&#44;3&#8208;8&#44;5&#41;&#46; Os &#237;ndices C&#47;M precoce e tardio foram significativamente menores nos doentes sintom&#225;ticos&#44; enquanto o <span class="elsevierStyleItalic">WR</span> foi significativamente mais elevado nesses doentes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Durante um seguimento mediano de 4&#44;5 anos &#40;DIQ&#58; 2&#44;1&#8208;7&#44;7&#59; m&#225;ximo&#58; 15&#44;6&#41;&#44; 121 doentes foram submetidos a cintigrafias seriadas&#44; incluindo pelo menos cinco exames em 36 doentes &#40;m&#225;ximo&#58; 9&#41; &#8211; <a class="elsevierStyleCrossRef" href="#sec0085">Tabela Suplementar 1</a>&#46; Considerando a avalia&#231;&#227;o inicial e as avalia&#231;&#245;es subsequentes&#44; foram realizadas um total de 558 cintigrafias MIBG na popula&#231;&#227;o estudada&#46; Nestes exames&#44; o &#237;ndice C&#47;M tardio diminuiu com a idade &#40;0&#44;082 por ano&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; e com a dura&#231;&#227;o dos sintomas &#40;0&#44;066 por ano&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; &#8211; <a class="elsevierStyleCrossRef" href="#fig0005">Figura 1</a> e <a class="elsevierStyleCrossRef" href="#sec0085">Appendix B</a>&#44; de forma similar em ambos os sexos &#40;<a class="elsevierStyleCrossRef" href="#sec0085">Appendix B</a>&#41;&#46; Na <a class="elsevierStyleCrossRef" href="#fig0010">Figura 2</a> &#233; apresentada a progress&#227;o do &#237;ndice C&#47;M tardio em cintigrafias MIBG seriadas de dois doentes exemplificativos&#44; ilustrando a lenta redu&#231;&#227;o na fase pr&#233;&#8208;sintom&#225;tica da doen&#231;a&#44; o decl&#237;nio mais pronunciado do &#237;ndice C&#47;M tardio ap&#243;s o in&#237;cio dos sintomas e a aparente estabiliza&#231;&#227;o ap&#243;s o transplante hep&#225;tico&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Estratifica&#231;&#227;o progn&#243;stica</span><p id="par0070" class="elsevierStylePara elsevierViewall">Durante o seguimento&#44; 47 doentes &#40;20&#44;3&#37;&#41; morreram&#46; A causa mais frequente de morte foi a PAF terminal&#44; correspondendo a 40&#37; de todas as causas de morte &#40;<a class="elsevierStyleCrossRef" href="#sec0085">Appendix B</a>&#41;&#46; O &#237;ndice C&#47;M tardio da cintigrafia inicial foi um forte preditor da mortalidade&#44; tendo o risco relativo de morte por qualquer causa aumentado em 27&#44;8&#37; &#40;intervalo de confian&#231;a de 95&#37; &#91;IC95&#37;&#93; 17&#44;5&#8208;39&#44;1&#41; por cada d&#233;cimo de redu&#231;&#227;o do &#237;ndice C&#47;M tardio &#40;<span class="elsevierStyleItalic">hazard ratio</span> &#91;HR&#93;&#58; 0&#44;78&#59; IC95&#37; 0&#44;72&#8208;0&#44;85&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Dos par&#226;metros do MIBG&#44; o &#250;nico preditor independente do progn&#243;stico foi o &#237;ndice C&#47;M tardio &#8211; <a class="elsevierStyleCrossRef" href="#tbl0010">Tabela 2</a>&#46; A mortalidade foi nove vezes mais elevada nos doentes com &#237;ndices C&#47;M mais reduzidos aquando da avalia&#231;&#227;o inicial &#40;ou seja 1&#46;&#176; quartil&#44; <span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1&#44;55&#41;&#44; quando comparada com os indiv&#237;duos com &#237;ndice C&#47;M acima do valor mediano da popula&#231;&#227;o &#40;ou seja<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>1&#44;83&#59; HR&#58; 9&#44;36&#59; IC95&#37; 4&#44;27&#8208;20&#44;56&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Al&#233;m disso&#44; a mortalidade foi quatro vezes mais elevada em doentes com redu&#231;&#227;o moderada do &#237;ndice C&#47;M tardio&#44; ou seja entre 1&#44;55&#8208;1&#44;83 &#40;HR&#58; 4&#44;27 IC95&#37; 1&#44;68&#8208;9&#44;05&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41; &#8211; <a class="elsevierStyleCrossRef" href="#fig0015">Figura 3</a>A&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Para determinar a eventual utilidade acrescida da avalia&#231;&#227;o seriada do &#237;ndice C&#47;M tardio para finalidade de estratifica&#231;&#227;o progn&#243;stica&#44; avaliou&#8208;se a precis&#227;o da totalidade das cintigrafias com MIBG realizadas na previs&#227;o da sobrevida p&#243;s&#8208;exame&#46; Portanto&#44; considerando os 558 exames realizados e um total de 2246 doentes&#8208;ano de seguimento&#44; verificou&#8208;se uma redu&#231;&#227;o significativa da sobreviv&#234;ncia p&#243;s&#8208;exame com a diminui&#231;&#227;o do &#237;ndice C&#47;M tardio&#46; Assim&#44; a mortalidade aumentou 29&#37; por cada decl&#237;nio decimal do &#237;ndice C&#47;M tardio &#40;HR&#58; 0&#44;774&#44; IC95&#37; 0&#44;73&#8208;0&#44;82&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; sendo nove vezes mais elevada nos doentes pertencentes ao 1&#46;&#176; quartil do &#237;ndice C&#47;M tardio &#40;HR&#58; 9&#44;15&#59; IC95&#37; 5&#44;44 &#8208;15&#44;38&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; &#8211; <a class="elsevierStyleCrossRef" href="#fig0015">Figura 3</a>B&#46; A precis&#227;o da previs&#227;o progn&#243;stica baseada nas avalia&#231;&#245;es seriadas foi determinada pela an&#225;lise das curvas ROC para v&#225;rios intervalos de tempo e comparada com a estratifica&#231;&#227;o progn&#243;stica baseada apenas na cintigrafia com MIBG inicial &#8211; <a class="elsevierStyleCrossRef" href="#tbl0015">Tabela 3</a>&#46; A precis&#227;o da estratifica&#231;&#227;o progn&#243;stica baseada em exames seriados foi ligeiramente superior&#44; mas as diferen&#231;as foram irris&#243;rias para os intervalos de tempo abaixo da mediana do seguimento dispon&#237;vel &#40;ou seja&#44; 4&#44;5 anos&#41;&#46; O poder estat&#237;stico da estratifica&#231;&#227;o progn&#243;stica baseada num &#250;nico exame ou em exames seriados foi semelhante e muito elevado&#58; 99&#37;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Impacto da transplanta&#231;&#227;o hep&#225;tica na progress&#227;o da inerva&#231;&#227;o simp&#225;tica mioc&#225;rdica avaliada por cintigrafia com MIBG&#8208;I<span class="elsevierStyleSup">123</span></span><p id="par0080" class="elsevierStylePara elsevierViewall">Setenta doentes &#40;30&#44;2&#37;&#41; foram submetidos a transplante hep&#225;tico&#46; Em 39 destes doentes&#44; a cirurgia foi realizada menos de um ano ap&#243;s a avalia&#231;&#227;o inicial&#46; A mortalidade perioperat&#243;ria foi de 7&#44;1&#37; &#40;5&#47;70&#41;&#46; Para determinar o impacto da transplanta&#231;&#227;o hep&#225;tica na progress&#227;o da inerva&#231;&#227;o simp&#225;tica&#44; comparou&#8208;se a taxa de redu&#231;&#227;o do &#237;ndice de capta&#231;&#227;o C&#47;M tardio nas imagens realizadas antes do transplante hep&#225;tico &#40;116 exames&#41; com a diminui&#231;&#227;o do &#237;ndice de capta&#231;&#227;o C&#47;M tardio nas imagens adquiridas posteriormente &#40;100 exames&#41;&#46; Dos exames efetuados antes da cirurgia&#44; 53 foram realizados durante o ano que antecedeu o transplante&#46; Nos doentes sintom&#225;ticos que necessitaram de transplante hep&#225;tico&#44; o &#237;ndice C&#47;M tardio diminuiu a uma taxa de 0&#44;19&#47;ano &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; antes do procedimento&#46; Al&#233;m disso&#44; o &#237;ndice C&#47;M precoce tamb&#233;m diminuiu progressivamente e o <span class="elsevierStyleItalic">WR</span> de MIBG aumentou&#46; Pelo contr&#225;rio&#44; todos os par&#226;metros MIBG estabilizaram ap&#243;s o transplante hep&#225;tico&#44; n&#227;o apresentando diferen&#231;as estatisticamente significativas ao longo do tempo &#8211; <a class="elsevierStyleCrossRef" href="#tbl0020">Tabela 4</a> e <a class="elsevierStyleCrossRef" href="#fig0020">Figura 4</a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discuss&#227;o</span><p id="par0085" class="elsevierStylePara elsevierViewall">Neste grande estudo prospetivo de portadores da muta&#231;&#227;o TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M&#44; seguidos durante uma mediana de 4&#44;5 anos&#44; caracteriz&#225;mos a progress&#227;o da desnerva&#231;&#227;o simp&#225;tica card&#237;aca&#44; avaliada pelo &#237;ndice de capta&#231;&#227;o C&#47;M de MIBG&#44; a import&#226;ncia do &#237;ndice na sobreviv&#234;ncia a longo prazo e o impacto do transplante hep&#225;tico na progress&#227;o da desnerva&#231;&#227;o card&#237;aca&#46; Os resultados mais relevantes s&#227;o os seguintes&#58; &#40;1&#41; a desnerva&#231;&#227;o card&#237;aca progride lentamente na fase pr&#233;&#8208;sintom&#225;tica da doen&#231;a&#44; mas tende a diminuir de forma mais acentuada ap&#243;s o in&#237;cio dos sintomas&#59; &#40;2&#41; o &#237;ndice C&#47;M tardio &#233; um forte preditor de progn&#243;stico&#44; aumentando o risco de morte em 27&#44;8&#37; para cada redu&#231;&#227;o decimal do &#237;ndice C&#47;M tardio&#59; e &#40;3&#41; o transplante hep&#225;tico&#44; amplamente utilizado para atenuar a progress&#227;o neurol&#243;gica da PAF&#44; estabiliza a desnerva&#231;&#227;o card&#237;aca no seguimento a longo prazo&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">As manifesta&#231;&#245;es cardiovasculares da PAF TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M s&#227;o causadas por disfun&#231;&#227;o auton&#243;mica &#40;dist&#250;rbios do controlo da press&#227;o arterial e da frequ&#234;ncia card&#237;aca&#41; e por deposi&#231;&#227;o card&#237;aca de amiloide &#40;miocardiopatia infiltrativa&#44; arritmias e defeitos de condu&#231;&#227;o&#41;&#46; No entanto&#44; existem diferen&#231;as fenot&#237;picas entre os doentes com a muta&#231;&#227;o TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M dependente da origem geogr&#225;fica&#46; Estudos de coortes de doentes suecos com TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M descrevem uma elevada preval&#234;ncia de miocardiopatia restritiva<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">3&#44;14</span></a>&#44; a qual &#233; bastante rara em doentes portugueses&#44; onde a neuropatia auton&#243;mica card&#237;aca e os defeitos de condu&#231;&#227;o tendem a dominar o quadro cl&#237;nico<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Estudos pr&#233;vios mostraram que a cintigrafia com MIBG permite visualizar indiretamente o compromisso da inerva&#231;&#227;o simp&#225;tica card&#237;aca devido a dep&#243;sito amiloide&#46; Nakata et al&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">15</span></a> foram os primeiros a relatar um caso de um doente com PAF TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M que apresentava aus&#234;ncia da atividade mioc&#225;rdica de MIBG&#44; indicando comprometimento dos nervos simp&#225;ticos&#46; Pequenos estudos subsequentes relataram n&#227;o s&#243; uma forte correla&#231;&#227;o entre a desnerva&#231;&#227;o mioc&#225;rdica e a gravidade da polineuropatia<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">16</span></a>&#44; mas tamb&#233;m que a redu&#231;&#227;o da capta&#231;&#227;o de MIBG pode ocorrer antes do desenvolvimento de doen&#231;a card&#237;aca&#44; clinicamente aparente<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">5</span></a>&#46; Num estudo anterior&#44; envolvendo 143 indiv&#237;duos&#44; document&#225;mos que as anomalias cardiovasculares avaliadas por ECG&#44; <span class="elsevierStyleItalic">Holter</span>&#44; monitoriza&#231;&#227;o ambulat&#243;ria da press&#227;o arterial&#44; ecocardiograma e cintigrafia com MIBG s&#227;o muito comuns na PAF TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M&#44; particularmente em doentes com atingimento neurol&#243;gico<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a>&#46; Em contraste com outras formas de amiloidose sist&#233;mica&#44; as anomalias cardiovasculares no nosso estudo foram&#44; geralmente&#44; subcl&#237;nicas e as manifesta&#231;&#245;es card&#237;acas &#243;bvias foram bastante raras&#46; No entanto&#44; verific&#225;mos que as manifesta&#231;&#245;es cardiovasculares subcl&#237;nicas antecedem muitas vezes o envolvimento neurol&#243;gico&#44; oferecendo uma oportunidade para o reconhecimento atempado do in&#237;cio da doen&#231;a em portadores assintom&#225;ticos&#46; Al&#233;m disso&#44; demonstr&#225;mos o valor progn&#243;stico das cintigrafias com MIBG&#44; as quais foram&#44; na realidade&#44; o preditor progn&#243;stico mais forte entre os v&#225;rios par&#226;metros card&#237;acos e neurol&#243;gicos avaliados&#46; Os doentes com desnerva&#231;&#227;o card&#237;aca detetada pelo &#237;ndice C&#47;M inferior a 1&#44;60 apresentaram um risco de morte sete vezes maior&#44; durante o seguimento&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A presente an&#225;lise confirma esses achados pr&#233;vios numa popula&#231;&#227;o mais alargada e estende os resultados atrav&#233;s da realiza&#231;&#227;o de avalia&#231;&#245;es seriadas do &#237;ndice C&#47;M&#46; Como esperado&#44; o &#237;ndice C&#47;M tardio diminuiu significativamente ao longo do tempo&#44; mas a progress&#227;o da desnerva&#231;&#227;o card&#237;aca foi t&#227;o lenta que a repeti&#231;&#227;o anual das cintigrafias com MIBG n&#227;o aumentou a precis&#227;o progn&#243;stica para prever a morte por qualquer causa&#46; Portanto&#44; o nosso estudo sugere que a avalia&#231;&#227;o repetida do &#237;ndice C&#47;M&#44; para fins de estratifica&#231;&#227;o do progn&#243;stico&#44; n&#227;o se justifica&#44; pelo menos se for realizada a intervalos de tempo menores do que cinco anos &#40;a dura&#231;&#227;o mediana de seguimento do presente estudo&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">O transplante hep&#225;tico tem sido largamente utilizado nos &#250;ltimos vinte anos para remover a principal fonte de produ&#231;&#227;o da transtirretina mutante&#44; travar a progress&#227;o das manifesta&#231;&#245;es cl&#237;nicas da doen&#231;a&#44; incluindo a neuropatia perif&#233;rica&#44; os sintomas gastrointestinais e outras complica&#231;&#245;es viscerais<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">7&#44;17&#8211;20</span></a>&#46; Al&#233;m disso&#44; o transplante tem um impacto favor&#225;vel na sobreviv&#234;ncia a longo prazo&#44; especialmente se for realizado nas fases iniciais da doen&#231;a sintom&#225;tica<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">6&#44;21</span></a>&#46; No entanto&#44; o impacto do transplante hep&#225;tico na progress&#227;o da miocardiopatia na TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M permanece controverso&#46; Alguns estudos sugeriram que os doentes transplantados n&#227;o desenvolvem miocardiopatia evidente<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">22&#44;23</span></a>&#44; enquanto outros&#44; em doentes suecos<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">10&#44;13</span></a>&#44; franceses<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> e japoneses<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a>&#44; relataram progress&#227;o de arritmias e espessamento do mioc&#225;rdio&#44; devido &#224; deposi&#231;&#227;o de amiloide&#46; Esta progress&#227;o adversa parece ser mais frequente em doentes suecos com in&#237;cio tardio da TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">3&#44;10&#44;13</span></a>&#46; Tem sido sugerido que o principal componente dos dep&#243;sitos card&#237;acos de amiloide que se estabelecem ap&#243;s a transplanta&#231;&#227;o hep&#225;tica &#233; a transtirretina normal &#40;<span class="elsevierStyleItalic">wild type TT</span>&#8221;&#41;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a>&#46; No entanto&#44; nenhum dos estudos que avaliaram a progress&#227;o ecocardiogr&#225;fica da infiltra&#231;&#227;o de amiloide&#44; ap&#243;s o transplante hep&#225;tico&#44; avaliou o seu impacto na inerva&#231;&#227;o auton&#243;mica card&#237;aca&#46; Num pequeno grupo de 31 doentes franceses&#44; Delahaye et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> compararam o &#237;ndice C&#47;M antes e ap&#243;s o transplante hep&#225;tico e complementaram com a avalia&#231;&#227;o ecocardiogr&#225;fica&#46; De forma semelhante aos nossos resultados&#44; n&#227;o foi encontrada nenhuma altera&#231;&#227;o na inerva&#231;&#227;o simp&#225;tica ap&#243;s o transplante hep&#225;tico durante um curto per&#237;odo de dura&#231;&#227;o de seguimento &#40;24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15 meses&#41;&#44; apesar de a infiltra&#231;&#227;o card&#237;aca de amiloide&#44; traduzida pela espessura mioc&#225;rdica&#44; ter progredido&#46; No presente estudo&#44; que envolveu um grupo maior de 70 doentes transplantados&#44; comparou&#8208;se a taxa de decr&#233;scimo do &#237;ndice C&#47;M antes do transplante hep&#225;tico &#40;116 cintigrafias&#41; com aquela dos exames efetuados posteriormente &#40;100 cintigrafias&#41;&#46; De forma relevante&#44; verificou&#8208;se estabiliza&#231;&#227;o de todos os par&#226;metros do MIBG ap&#243;s a cirurgia&#46; Portanto&#44; parece existir uma dissocia&#231;&#227;o clara entre a deposi&#231;&#227;o de amiloide &#40;avaliada ecocardiograficamente pela espessura mioc&#225;rdica&#41; que poder&#225; progredir&#44; e o envolvimento dos nervos card&#237;acos auton&#243;micos&#44; que tende a estabilizar&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclus&#245;es</span><p id="par0110" class="elsevierStylePara elsevierViewall">A desnerva&#231;&#227;o card&#237;aca &#233; relevante na progress&#227;o da PAF TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M e avalia&#231;&#227;o do &#237;ndice C&#47;M tardio &#233; importante para a estratifica&#231;&#227;o do progn&#243;stico destes doentes&#46; O transplante hep&#225;tico permite estabilizar a desnerva&#231;&#227;o card&#237;aca&#46; Ap&#243;s o transplante&#44; a capta&#231;&#227;o card&#237;aca de MIBG&#8208;I<span class="elsevierStyleSup">123</span> permanece est&#225;vel ao longo do tempo&#44; sem recupera&#231;&#227;o ou deteriora&#231;&#227;o adicional&#46; Assim&#44; &#233; crucial que o transplante seja realizado numa fase suficientemente precoce da hist&#243;ria natural da doen&#231;a&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Responsabilidades &#233;ticas</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Prote&#231;&#227;o de pessoas e animais</span><p id="par0115" class="elsevierStylePara elsevierViewall">Os autores declaram que os procedimentos seguidos estavam de acordo com os regulamentos estabelecidos pelos respons&#225;veis da Comiss&#227;o de Investiga&#231;&#227;o Cl&#237;nica e &#201;tica e de acordo com os da Associa&#231;&#227;o M&#233;dica Mundial e da Declara&#231;&#227;o de Helsinki&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Confidencialidade dos dados</span><p id="par0120" class="elsevierStylePara elsevierViewall">Os autores declaram ter seguido os protocolos do seu centro de trabalho acerca da publica&#231;&#227;o dos dados de pacientes&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Direito &#224; privacidade e consentimento escrito</span><p id="par0125" class="elsevierStylePara elsevierViewall">Os autores declaram que n&#227;o aparecem dados de pacientes neste artigo&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflito de interesses</span><p id="par0130" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflito de interesses&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamenta&#231;&#227;o</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A polineuropatia amiloid&#243;tica familiar &#40;PAF&#41; &#233; uma doen&#231;a rara devida &#224; deposi&#231;&#227;o sist&#233;mica de variantes amiloidog&#233;nicas da prote&#237;na transtirretina &#40;TTR&#41;&#46; A TTR&#8208;V30M consiste na substitui&#231;&#227;o da valina pela metionina na posi&#231;&#227;o 30 e atinge especialmente o sistema nervoso perif&#233;rico e auton&#243;mico&#46; As manifesta&#231;&#245;es cardiovasculares s&#227;o muito comuns e devem&#8208;se &#224; desnerva&#231;&#227;o auton&#243;mica e &#224; deposi&#231;&#227;o de amiloide no cora&#231;&#227;o&#46; A desnerva&#231;&#227;o simp&#225;tica card&#237;aca&#44; detetada por cintigrafia com metaiodobenzilguanidina &#40;MIBG&#41; marcada com I<span class="elsevierStyleSup">123</span>&#44; &#233; um importante estratificador progn&#243;stico na PAF TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M&#46; O transplante hep&#225;tico&#44; amplamente utilizado para interromper a progress&#227;o do envolvimento neurol&#243;gico&#44; parece ter impacto heterog&#233;neo na evolu&#231;&#227;o da miocardiopatia amiloid&#243;tica&#46; O seu impacto na progress&#227;o da desnerva&#231;&#227;o card&#237;aca permanece desconhecido&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudo observacional de portadores da muta&#231;&#227;o TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M submetidos a avalia&#231;&#227;o cardiol&#243;gica anual e a cintigrafias com MIBG seriadas&#44; com quantifica&#231;&#227;o do &#237;ndice de capta&#231;&#227;o cora&#231;&#227;o&#47;mediastino &#40;C&#47;M&#41; tardio&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Foram estudados 232 doentes &#40;idade mediana de 40 anos&#44; 54&#44;7&#37; do sexo feminino&#44; 37&#44;9&#37; assintom&#225;ticos aquando da inclus&#227;o&#41;&#44; seguidos durante uma mediana de 4&#44;5 anos e submetidos a um total de 558 cintigrafias MIBG&#46; Durante o seguimento&#44; 47 doentes &#40;20&#44;3&#37;&#41; morreram&#46; A cintigrafia com MIBG inicial foi um forte preditor progn&#243;stico&#44; detetando&#8208;se aumento do risco de morte em 27&#44;8&#37; por cada redu&#231;&#227;o decimal do &#237;ndice C&#47;M tardio&#46; O &#237;ndice C&#47;M tardio diminuiu com a idade &#40;0&#44;082 por ano&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; mas a progress&#227;o da desnerva&#231;&#227;o card&#237;aca foi t&#227;o lenta que a repeti&#231;&#227;o anual do exame n&#227;o aumentou a sua precis&#227;o progn&#243;stica&#46; Durante o seguimento&#44; 70 doentes sintom&#225;ticos foram submetidos a transplante hep&#225;tico&#46; O &#237;ndice C&#47;M tardio diminuiu 0&#44;19&#47;ano at&#233; ao transplante&#44; deixando de ser detetadas varia&#231;&#245;es estatisticamente significativas a partir do procedimento&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclus&#227;o</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A desnerva&#231;&#227;o card&#237;aca &#233; frequente durante a progress&#227;o da PAF TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M e a quantifica&#231;&#227;o do &#237;ndice C&#47;M tardio por cintigrafia MIBG &#233; valiosa para a estratifica&#231;&#227;o progn&#243;stica destes doentes&#46; O transplante hep&#225;tico permite a estabiliza&#231;&#227;o da desnerva&#231;&#227;o card&#237;aca&#44; n&#227;o havendo recupera&#231;&#227;o ou deteriora&#231;&#227;o adicional da capta&#231;&#227;o card&#237;aca de MIBG ap&#243;s o procedimento&#46;</p></span>"
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            "identificador" => "abst0020"
            "titulo" => "Conclus&#227;o"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Familial amyloid polyneuropathy &#40;FAP&#41; is a rare disease caused by systemic deposition of amyloidogenic variants of the transthyretin &#40;TTR&#41; protein&#46; The TTR&#8208;V30M mutation is caused by the substitution of valine by methionine at position 30 and mainly affects the peripheral and autonomic nervous systems&#46; Cardiovascular manifestations are common and are due to autonomic denervation and to amyloid deposition in the heart&#46; Cardiac sympathetic denervation detected by iodine&#8208;123 labeled metaiodobenzylguanidine &#40;MIBG&#41; is an important prognostic marker in TTR&#8208;V30M FAP&#46; Liver transplantation&#44; widely used to halt neurological involvement&#44; appears to have a varying effect on the progression of amyloid cardiomyopathy&#46; Its effect on the progression of cardiac denervation remains unknown&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">In this observational study&#44; patients with the TTR&#8208;V30M mutation underwent annual cardiac assessment and serial MIBG imaging with quantification of the late heart&#8208;to&#8208;mediastinum &#40;H&#47;M&#41; ratio&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">We studied 232 patients &#40;median age 40 years&#44; 54&#46;7&#37; female&#44; 37&#46;9&#37; asymptomatic at the time of inclusion&#41; who were followed for a median of 4&#46;5 years and underwent a total of 558 MIBG scans&#46; During follow&#8208;up&#44; 47 patients &#40;20&#46;3&#37;&#41; died&#46; MIBG scintigraphy at inclusion was a strong predictor of prognosis&#44; with the risk of death increasing by 27&#46;8&#37; for each one&#8208;tenth reduction in the late H&#47;M ratio&#46; The late H&#47;M ratio decreased with age &#40;0&#46;082&#47;year&#44; p&#60;0&#46;001&#41;&#44; but progression of cardiac denervation was so slow that annual repetition of MIBG imaging did not increase its prognostic accuracy&#46; During follow&#8208;up&#44; 70 symptomatic patients underwent liver transplantation&#46; The late H&#47;M ratio decreased by 0&#46;19&#47;year until transplantation but no statistically significant differences were detected after the procedure&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">Cardiac denervation is common during the progression of TTR&#8208;V30M FAP and quantification of the late H&#47;M ratio on MIBG scintigraphy is valuable for prognostic stratification of these patients&#46; Liver transplantation stabilizes cardiac denervation&#44; without recovery or further deterioration in cardiac MIBG uptake after the procedure&#46;</p></span>"
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            "identificador" => "abst0025"
            "titulo" => "Introduction"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
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      ]
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          0 => array:4 [
            "apendice" => "<p id="par0140" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Material suplementario"
            "identificador" => "sec0085"
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        ]
      ]
    ]
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Varia&#231;&#227;o do &#237;ndice C&#47;M tardio em fun&#231;&#227;o da idade &#40;A&#41; e da dura&#231;&#227;o dos sintomas &#40;B&#41;&#46;</p>"
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Varia&#231;&#227;o do &#237;ndice C&#47;M tardio ao longo do tempo em dois doentes com PAF TTR&#8208;V30<span class="elsevierStyleHsp" style=""></span>M&#44; mostrando a diminui&#231;&#227;o do &#237;ndice com a progress&#227;o da doen&#231;a e a aparente estabiliza&#231;&#227;o ap&#243;s a transplanta&#231;&#227;o hep&#225;tica&#46;</p>"
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        "mostrarDisplay" => false
        "figura" => array:1 [
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          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Sobreviv&#234;ncia em fun&#231;&#227;o da distribui&#231;&#227;o por quartis do &#237;ndice C&#47;M&#44; considerando a primeira cintigrafia &#40;A&#41; e a totalidade das cintigrafias realizadas durante o seguimento&#46;</p>"
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        "mostrarFloat" => true
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        "figura" => array:1 [
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          "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Varia&#231;&#227;o do &#237;ndice C&#47;M tardio ao longo do tempo decorrido antes e ap&#243;s a transplanta&#231;&#227;o hep&#225;tica&#46;</p>"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">C&#47;M&#58; capta&#231;&#227;o de MIBG cora&#231;&#227;o&#47;mediastino&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Valor de p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#205;ndice C&#47;M tardio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;09<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;31&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Washout rate</span> do MIBG&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Compara&#231;&#227;o dos par&#226;metros de MIBG em fun&#231;&#227;o do envolvimento neurol&#243;gico</p>"
        ]
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            "detalle" => "Tabela "
            "rol" => "short"
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">C&#47;M&#58; capta&#231;&#227;o de MIBG cora&#231;&#227;o&#47;mediastino&#59; DIQ&#58; distribui&#231;&#227;o interquartis&#59; HR&#58; <span class="elsevierStyleItalic">hazard ratio</span>&#59; IC95&#37;&#58; intervalo de confian&#231;a de 95&#37;&#59; NS&#58; n&#227;o significativo&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Vari&#225;vel&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Valor de p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Idade&#44; mediana &#40;DIQ&#41;&#44; anos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#205;ndice C&#47;M precoce&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;085&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#205;ndice C&#47;M tardio&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;086&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;037&#8208;0&#44;199&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;183&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS &#40;0&#44;134&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;037&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;008&#8208;1&#44;066&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1425532.png"
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Mortalidade durante o seguimento&#44; em fun&#231;&#227;o da idade e dos par&#226;metros de MIBG na avalia&#231;&#227;o inicial</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">AUC&#58; &#225;rea sob a curva <span class="elsevierStyleItalic">receiver operator characteristic</span>&#46; Todas as outras abreviaturas conforme a <a class="elsevierStyleCrossRef" href="#tbl0010">Tabela 2</a>&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Vari&#225;vel&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Avalia&#231;&#227;o do &#237;ndice C&#47;M tardio na inclus&#227;o<br>&#40;232 scans em 232 doentes&#41;</th><th class="td" title="table-head  " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Avalia&#231;&#245;es repetidas do &#237;ndice C&#47;M tardio por doente<br>&#40;558 scans em 232 doentes&#41;</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Doentes&#8208;ano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N&#250;mero de eventos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AUC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IC95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Valor de p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Doentes&#8208;ano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N&#250;mero de eventos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AUC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IC95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Valor de p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Qualquer momento do seguimento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1171&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;65&#8208;0&#44;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2583&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;67&#8208;0&#44;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aos 12 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">109&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;58&#8208;0&#44;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS &#40;0&#44;131&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">457&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;77&#8208;0&#44;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aos 24 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">352&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;75&#8208;0&#44;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">806&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;77&#8208;0&#44;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aos 36 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">467&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;69&#8208;0&#44;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1097&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;71&#8208;0&#44;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aos 48 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">534&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;66&#8208;0&#44;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1261&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;72&#8208;0&#44;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aos 60 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">553&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;68&#8208;0&#44;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1268&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;72&#8208;0&#44;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1425534.png"
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Precis&#227;o dos modelos de predi&#231;&#227;o da mortalidade avaliada pela an&#225;lise de curvas <span class="elsevierStyleItalic">receiver operator characteristic analysis</span> &#40;ROC&#41;</p>"
        ]
      ]
      7 => array:8 [
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        "etiqueta" => "Tabela 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
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            "identificador" => "at4"
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            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Abreviaturas conforme a <a class="elsevierStyleCrossRef" href="#tbl0010">Tabela 2</a>&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Vari&#225;vel&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Pr&#233;&#8208;transplanta&#231;&#227;o hep&#225;tica</th><th class="td" title="table-head  " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">P&#243;s&#8208;transplanta&#231;&#227;o hep&#225;tica</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Correla&#231;&#227;o de Pearson</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Correla&#231;&#227;o de Spearman</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Correla&#231;&#227;o de Pearson</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Correla&#231;&#227;o de Spearman</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Valor de p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Rho&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Valor de p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Valor de p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Rho&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Valor de p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#205;ndice C&#47;M precoce&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8208;0&#44;322&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8208;0&#44;216&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;144&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS &#40;0&#44;154&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;180&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS &#40;0&#44;073&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#205;ndice C&#47;M tardio&nbsp;\t\t\t\t\t\t\n
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