Transthyretin amyloid cardiomyopathy | Medicina Clínica (English Edition)

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Amyloidosis is a systemic disease characterized by extracellular amyloid deposition&#44; which can affect any organ or system&#44; altering its structure and function&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Amyloid fibrils are formed by normal soluble proteins that undergo a conformational change and are deposited as insoluble fibrils&#46; The term amyloid defines the presence of material that&#44; with Congo red staining&#44; exhibits apple-green birefringence under polarized light&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">There are more than 30 human amyloid precursor proteins&#46; Of all of them&#44; only nine lead to significant cardiac involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0020" class="elsevierStylePara elsevierViewall">Light chains&#44; leading to AL amyloidosis &#40;previously called primary amyloidosis&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0025" class="elsevierStylePara elsevierViewall">Transthyretin &#40;TTR&#41;&#44; causing transthyretin amyloidosis &#40;ATTR&#41;&#44; both in its hereditary or genetic form &#40;ATTRv&#41; and in its non-hereditary or wild-type &#40;ATTRwt&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0030" class="elsevierStylePara elsevierViewall">There are other less common forms&#58; by serum component A &#40;AA&#41;&#44; apolipoprotein AI&#44; apolipoprotein AII&#44; apolipoprotein AIV&#44; &#946;2-microglobulin&#44; fibrinogen A-&#945; or gelsolin&#46;</p></li></ul></p><p id="par0035" class="elsevierStylePara elsevierViewall">Most patients with cardiac amyloidosis &#40;CA&#41; have AL-CA or ATTR-CA&#46; Although AL has traditionally been considered the most common form of CA in developed countries&#44; ATTR-CA is currently the most common form&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The improvement in imaging techniques&#44; the possibility of non-invasive diagnosis&#44; and the development of specific therapies have increased interest in this disease&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Transthyretin amyloid cardiomyopathy</span><p id="par0040" class="elsevierStylePara elsevierViewall">ATTR is the result of TTR deposition&#44; a tetrameric plasma protein whose function is to transport thyroxine and retinol-bound protein&#46; TTR is mainly synthesized in the liver&#44; although also to a lesser extent in other locations such as the choroid plexuses or the retina&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">TTR has a predisposition to disintegrate into dimers and monomers&#44; either by a mutation that gives rise to an unstable protein in ATTRv or by other factors associated with age in ATTRwt&#46; TTR monomers assemble into fibrils&#44; depositing themselves in different organs and tissues&#44; but with a significant cardiac tropism for reasons not clearly established&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Non-hereditary TTR amyloidosis</span><p id="par0050" class="elsevierStylePara elsevierViewall">ATTRwt is a sporadic disease&#44; with mainly cardiac and soft tissue involvement&#44; with ligament and tendon depositions often precedes cardiac manifestations for years&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">It is a disease associated with aging&#44; reason why it was called senile amyloidosis until recently&#46; However&#44; the fact that patients &#60;60 years old have been reported has resulted in the term senile to be considered inappropriate&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Although its prevalence is not exactly known&#44; recent studies using diphosphonate scintigraphy have shown the true impact of this entity&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Between 13&#37;&#8211;19&#37; of patients &#8805;60 years of age hospitalized for heart failure &#40;HF&#41; with preserved ejection fraction &#40;HFpEF&#41; and left ventricular hypertrophy &#40;LVH&#41; &#8805;12<span class="elsevierStyleHsp" style=""></span>mm&#44; had ATTRwt as a cause of HF&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0070" class="elsevierStylePara elsevierViewall">From 12&#37; to 16&#37; of patients &#8805;65 years of age who underwent aortic valve replacement with a transcatheter prosthesis &#40;TAVI&#41; for aortic stenosis&#44; were diagnosed with concomitant ATTRwt&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;10</span></a></p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0075" class="elsevierStylePara elsevierViewall">In addition&#44; a Spanish study detected a prevalence of cardiac uptake in scintigraphy performed for non-cardiac indications of up to 3&#46;8&#37; in men and 0&#46;7&#37; in women in patients &#8805;75 years of age&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></li></ul></p><p id="par0080" class="elsevierStylePara elsevierViewall">Although ATTRwt was considered a quasi-exclusive male disease&#44; more recent data indicate that the incidence among women is higher than what was previously thought and may reach 20&#37; in some cohorts&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Hereditary TTR amyloidosis</span><p id="par0085" class="elsevierStylePara elsevierViewall">TTRv is an autosomal dominant disease with variable penetrance&#46; Although its prevalence is unknown&#44; it is considered a rare disease&#44; with a prevalence of less than 1 per 100&#44;000 inhabitants&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">There are more than 120 known mutations<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> with a strong genotype-phenotype correlation&#44; with some mutations that give rise to a predominantly neurological c&#59; while others&#44; such as Val142Ile&#44; Leu121Met or Ile88Leu&#44; mainly cause a cardiac condition&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">However&#44; recent data suggest that combined cardiac and neurologic involvement is common and that the spectrum of the disease is continuous&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The Val50Met mutation &#40;Val30Met according to the traditional nomenclature&#41; is endemically present in several countries &#40;Sweden&#44; Japan&#44; and Portugal&#41;&#46; In Spain&#44; there are also Val50Met endemic foci in Mallorca and in Valverde del Camino&#44; Huelva&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The Val50Met mutation is characterized by an early presentation &#40;&#60;50 years&#41; with neurological involvement in endemic areas and a late presentation &#40;&#62;50 years&#41;&#44; with greater cardiac involvement in non-endemic areas&#46; According to data from Mallorca&#44; cardiac involvement is more common than previously estimated&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Due to its relevance&#44; we also highlight the Val142Ile mutation &#40;Val122Ile according to traditional nomenclature&#41;&#44; which is present in about 3&#37; of black individuals in the United States&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The Val142Ile mutation results in a predominantly cardiac ATTR&#44; which can be superimposed on ATTRwt&#44; although with an earlier age of onset and mild neuropathy in up to 30&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Although the Val142Ile mutation is much more common among black subjects&#44; we have also found several Spanish Caucasian families with ATTRv due to the Val142Ile mutation&#44; without black ancestors&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the main differences between both forms of ATTR&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Presentation scenarios</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Cardiac manifestations</span><p id="par0120" class="elsevierStylePara elsevierViewall">CA has traditionally been included in the list of causes of restrictive cardiomyopathy&#46; However&#44; amyloid infiltration can also affect the conduction system&#44; valves&#44; and vessels&#44; resulting in multiple forms of clinical presentation&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Heart failure</span><p id="par0125" class="elsevierStylePara elsevierViewall">The most common form of presentation of ATTR-CA is as HF&#46; The prevalence of ATTRwt in HFpEF is 13&#37;&#8211;19&#37; in admitted patients &#62;60 years of age&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> However&#44; ATTR-CA does not only manifest itself as HFpEF&#46; Systolic function deteriorates as deposition progresses&#44; and up to a third of patients with ATTRwt have a left ventricular ejection fraction &#40;LVEF&#41; &#60;50&#37; at the time of diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Thus&#44; our group also found that 11&#37; of the subjects &#8805;60 years of age admitted for HF with LVEF &#60;50&#37; and LVH &#8805;12<span class="elsevierStyleHsp" style=""></span>mm suffered from ATTRwt&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Hypertrophic cardiomyopathy phenocopy</span><p id="par0130" class="elsevierStylePara elsevierViewall">5&#37; of cases of ATTRv have been reported in patients with LVH<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>mm &#40;limit considered to establish the diagnosis of hypertrophic cardiomyopathy&#41; although this result is determined by the origin of the population and the mean age of the patients studied&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conduction disorders</span><p id="par0135" class="elsevierStylePara elsevierViewall">Both atrioventricular and sinus conduction disorders may be the first manifestation of ATTR-CA&#44; although only 2&#37; of patients &#62;60 years of age who require pacemaker implantation without an underlying cause have ATTRwt&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Aortic stenosis</span><p id="par0140" class="elsevierStylePara elsevierViewall">The demographic characteristics of patients with ATTRwt and those with aortic stenosis are similar&#44; with studies that have established a prevalence that varies between 6&#37; in those undergoing surgical aortic valve replacement&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and up to 16&#37; among those who underwent TAVI&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The most common presentation in these patients is that of a low-flow&#44; low-gradient aortic stenosis&#44; with slightly reduced LVEF&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Extracardiac manifestations</span><p id="par0145" class="elsevierStylePara elsevierViewall">Extracardiac manifestations in ATTRwt include carpal tunnel syndrome &#40;CTS&#41;&#44; which usually precedes cardiac symptoms by 5&#8211;10 years&#59;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> atraumatic rupture of the long head of the proximal biceps brachii tendon &#40;&#8220;Popeye&#8217;s sign&#8221;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> lumbar canal stenosis<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and even sensorineural deafness&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Additionally&#44; 10&#37; neuropathy has been reported in ATTRwt&#44; with doubts as to whether it is a manifestation of the disease itself or is due to other etiologies&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The existence of bilateral CTS should always be investigated in subjects with LVH since the prevalence of CA in patients &#8805;60 years of age with LVH and bilateral CTS not associated with work activities can reach 13&#46;6&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">On the other hand&#44; neurological involvement in ATTRv is a symmetric sensory-motor polyneuropathy that initially manifests as dysesthesia&#44; paraesthesia&#44; and sensory loss from the lower limbs&#44; due to predominantly fine fibre involvement&#46; It ends up giving rise to pain in the lower limbs&#44; muscular atrophy&#44; weakness&#44; and problems with walking&#46; It can also associate autonomic nervous system involvement&#44; with orthostatic hypotension&#44; urinary and rectal incontinence&#44; unintended weight loss&#44; alternating constipation&#44; and diarrhoea&#44; as well as erectile dysfunction&#46; In ATTRv there may also be ophthalmological involvement &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; so regular ophthalmological evaluations are recommended&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">All these extra-cardiac signs and symptoms are considered signs suggestive of ATTR&#44; which should be suspected in the presence of LVH &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Diagnosis</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Diagnostic criteria</span><p id="par0165" class="elsevierStylePara elsevierViewall">Classically the diagnosis of ATTR-CA was based on the histological demonstration of amyloid followed by the identification of TTR as a precursor protein&#46; However&#44; the diagnosis can be made non-invasively by using bone-tracer scintigraphy in the appropriate clinical context &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Invasive diagnosis</span><p id="par0170" class="elsevierStylePara elsevierViewall">The presence of amyloid in an endomyocardial biopsy &#40;EMB&#41; confirms the diagnosis of CA&#46; Confirmation of ATTR will be done by immunohistochemistry or mass spectrometry to demonstrate that the deposit corresponds to TTR&#46; Mass spectrometry is considered the gold standard for establishing the amyloid subtype&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The risk of complications from EMB is low in experienced centres&#44; with a sensitivity close to 100&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">The diagnosis of CA can also be established if amyloid is demonstrated in extracardiac biopsies in the presence of LVH<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>mm in the absence of other causes that justify said LVH or in the presence of typical findings on cardiac magnetic resonance imaging &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">The profitability of extracardiac biopsies varies between ATTRwt and ATTRv and also depending on the location&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> A negative extracardiac biopsy of a clinically unaffected organ does not rule out the diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Therefore&#44; given the variable profitability according to site&#44; technique&#44; and experience&#44; we recommend performing a biopsy of the affected organ as soon as possible to avoid diagnostic delays&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Non-invasive diagnosis</span><p id="par0190" class="elsevierStylePara elsevierViewall">The non-invasive diagnosis of ATTR-CA can be made when characteristic data is present in cardiac echocardiography or magnetic resonance imaging&#44; cardiac uptake equal to or greater than bone &#40;grades 2 or 3&#41; in bone scintigraphy with <span class="elsevierStyleSup">99</span>Tc-DPD &#40;diisopropyl diphosphonate&#41;&#44; <span class="elsevierStyleSup">99</span>Tc-PYP &#40;pyrophosphate&#41; or <span class="elsevierStyleSup">99</span>Tc-HMDP &#40;hydroxymethyl diphosphonate&#41; and absence of monoclonal component &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">In order to rule out the presence of a monoclonal component&#44; three tests are required&#58; serum free light chains&#44; serum immunofixation electrophoresis and urine immunofixation electrophoresis&#46; The combination of the three has a sensitivity of 99&#37; for the identification of a pro-amyloidogenic precursor of AL amyloidosis&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> There is also cardiac uptake in 30&#37;&#8211;40&#37; of patients with AL-CA&#44; so it is vitally important to note that it is necessary to perform an immunofixation electrophoresis to increase sensitivity and to be able to detect the presence of a monoclonal protein&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">It has been described that this approach has a specificity and a positive predictive value close to 100&#37; for the diagnosis of ATTR-CA&#44; avoiding the need for a biopsy&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> However&#44; it should be taken into account that there are other situations that can also lead to cardiac uptake &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Diagnostic approach</span><p id="par0205" class="elsevierStylePara elsevierViewall">In all patients with suspected CA&#44; we recommend evaluation by bone scintigraphy&#44; serum free light chains&#44; blood&#44; and urine immunofixation&#46; Depending on the results&#44; we can find four scenarios &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#58;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0210" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Absence of cardiac uptake in normal haematological scintigraphy and tests&#46;</span> If the scintigraphy shows a total absence of cardiac uptake &#40;grade 0 uptake&#41; and the haematological tests show no abnormalities&#44; the probability of CA is very low&#44; although the possibility of a false negative scintigraphy should be considered &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; or the presence of a form of amyloidosis that does not correspond to AL or ATTR&#46; If suspicion persists&#44; EMB should be performed&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Cardiac uptake in scintigraphy and normal haematological tests&#46;</span> If uptake is grade 2 or 3 and no monoclonal component is detected&#44; a non-invasive diagnosis of ATTR can be established&#46; In the event that uptake is grade 1 &#40;cardiac uptake lower than in bone&#41;&#44; the diagnosis cannot be established&#44; and histological demonstration is necessary&#44; by means of cardiac or extracardiac biopsy&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Absence of cardiac uptake and abnormalities in any of the haematological tests&#46;</span> AL amyloidosis should be excluded by extracardiac or preferably cardiac biopsy to avoid a diagnostic delay that could determine a worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Cardiac uptake in scintigraphy and abnormalities in any of the haematological tests&#46;</span> We could be facing ATTR&#44; AL or the coexistence of both&#46; EMB is required to determine the subtype&#46; Diagnosis by extracardiac biopsy is usually not possible in this case&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Genetic study and evaluation of relatives</span><p id="par0230" class="elsevierStylePara elsevierViewall">In patients diagnosed with ATTR&#44; a genetic study should be carried out&#44; regardless of age&#44; since hereditary forms are found even in elderly patients&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> The difference between ATTRv and ATTRwt is of vital importance since it determines the need for evaluation of relatives and has prognostic and therapeutic implications&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">First-degree relatives of a patient with ATTRv have a 50&#37; chance of inheriting the genetic alteration&#46; Since ATTRv occurs during adulthood&#44; genetic testing in minors is not recommended&#46; We recommend its performance in early adulthood if the result of the genetic study may have implications for the individual&#8217;s professional or reproductive guidance&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Given that penetrance is incomplete and variable according to the different mutations&#44; it is recommended to start the clinical evaluation of relatives about 10 years before the age of onset of the disease in the family or in patients with the same mutation or as soon as compatible ATTRv symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Prognosis</span><p id="par0245" class="elsevierStylePara elsevierViewall">In recent years&#44; various prognostic systems similar to those used in AL-CA have emerged&#46; There are two proposed systems that combine two parameters and classify patients according to their presence&#46; The first is validated only for the ATTRwt form and uses the highly sensitive N-terminal pro-brain natriuretic peptide &#40;Nt-proBNP&#41; and troponin T with a cut-off of 3000<span class="elsevierStyleHsp" style=""></span>pg&#47;mL and 0&#46;05<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">The second proposal has been developed for ATTRv and ATTRwt and uses NTproBNP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3000<span class="elsevierStyleHsp" style=""></span>ng&#47;L and estimated glomerular filtration of &#60;45<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> &#40;using the MDRD formula&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> The advantages of this second scale are based on its validation in both types of ATTR and on the use of two commonly used biomarkers&#44; without including the different troponins with their different quantification methods&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Treatment</span><p id="par0255" class="elsevierStylePara elsevierViewall">Treatment of patients with TTR CA includes two areas&#46; On the one hand&#44; complications&#44; including HF and arrhythmias and&#44; on the other&#44; specific treatment to stop or slow the progression of the disease &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Supportive treatment and complications</span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Heart failure</span><p id="par0260" class="elsevierStylePara elsevierViewall">Hygienic-dietary measures aimed at avoiding congestion are especially important in patients with ATTR and HF&#46; Patients should be emphasized the importance of daily weight&#44; maintenance of a low-salt diet &#40;&#60;2<span class="elsevierStyleHsp" style=""></span>g&#47;day&#41; and water restriction &#40;&#8804;1&#46;5<span class="elsevierStyleHsp" style=""></span>L&#47;day&#41;&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">The mainstay of treatment for HF is loop diuretics&#46; We recommend preferably using those loop diuretics with higher bioavailability &#40;torasemide&#41; that can be given in combination with thiazides or mineralocorticoid receptor antagonists&#46; The latter are used at low doses to avoid hypokalaemia if high doses of diuretic are required&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">However&#44; diuretic management must be careful due to the restrictive pathophysiology of the disease&#44; which can lead to hypotension and clinical worsening&#46; Compression stockings and midodrine can help in cases of symptomatic hypotension due to dysautonomia or the need for high doses of diuretics&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">Unlike HF with systolic dysfunction&#44; there is no evidence of benefit of beta-blockers&#44; ACEIs&#44; AIIRAs&#44; sacubitril&#47;valsartan or ivabradine in ATTR&#46; Its use&#44; in fact&#44; can worsen the clinical situation or be poorly tolerated given the pathophysiology and compensatory tachycardia needed to maintain the cardiac output in this disease&#46; There are few published data in this regard&#44; but a study showed a worse prognosis in ATTRv patients receiving treatment with beta-blockers and ACE inhibitors&#44; with a neutral effect on ATTRwt&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Therefore&#44; in general&#44; they should be avoided&#44; and we recommend their discontinuation&#46; Beta-blockers could be used in selected cases for rate control in atrial fibrillation &#40;AF&#41;&#44; at low doses and carefully increasing them&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">On the other hand&#44; non-dihydropyridine calcium antagonists are considered contraindicated&#44; like digoxin&#44; due to the affinity of these drugs for amyloid fibrils&#44; which increases their biological effects and risk of toxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> However&#44; a recent study in AL patients has reopened the debate regarding the possible use of digoxin in CA&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">The experience of ventricular assist devices in ATTR-CA is restricted to a few cases or small series&#44; with variable results&#44; so the benefit of this option remains to be determined&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">Although heart transplantation has been a controversial option in some sites&#44; the most recent data have shown that the results of the last decade in ATTR-CA are comparable with other heart diseases&#44; probably due to a very careful selection of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Atrial fibrillation</span><p id="par0295" class="elsevierStylePara elsevierViewall">The management of AF in ATTR-CA constitutes a challenge in clinical practice&#46; The few studies carried out have found no differences in survival between patients in sinus rhythm versus AF&#44;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41&#44;42</span></a> so the decision between rhythm control or heart rate control must be individualized&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">In the case of opting for rhythm control&#44; amiodarone is the most widely used antiarrhythmic agent&#46; If electrical cardioversion &#40;ECV&#41; is required&#44; it should be considered a risky procedure and although the success rate may be similar to that of patients with other heart diseases&#44; patients with ATTR-CA have a higher risk of complications&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">Several studies have shown the common existence of intracardiac thrombi&#44; regardless of the time of onset of AF or correct anticoagulation&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> so it is always necessary to rule out the presence of pre-ECV thrombi&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> Pulmonary vein ablation in ATTR is controversial without being able to establish recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">Anticoagulation should always be initiated when AF is found&#44; since ATTR patients have a high risk of thromboembolism&#46; This decision must be independent of the CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc score&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">In addition&#44; anticoagulation in sinus rhythm can be considered on an individual basis&#44; taking into account the significant atrial dilation or low atrial rates in the transmitral flow pattern&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">Finally&#44; there are no solid data comparing direct-acting anticoagulants and vitamin K antagonists in ATTR-CA&#44; so both options are used interchangeably&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conduction disorders</span><p id="par0325" class="elsevierStylePara elsevierViewall">Infiltration of the conduction system or adjacent fibrosis can lead to the occurrence of chronotropic incompetence and conduction disorders of the sinus node or the atrioventricular node&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">The indications for pacemaker implantation in ATTR follow current guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> Beyond these indications&#44; some groups promote the prophylactic implantation of pacemakers in ATTRv&#46; In favour of this proposal&#44; it was described that in a cohort of ATTRv in which a pacemaker had been implanted prophylactically &#40;taking into account one of the following conduction parameters measured in an electrophysiological study&#58; His-ventricle interval &#8805;70<span class="elsevierStyleHsp" style=""></span>ms&#44; His-ventricular interval &#62;55<span class="elsevierStyleHsp" style=""></span>ms associated with fascicular block&#44; first degree AV block or antegrade Wenckebach point &#8804;100<span class="elsevierStyleHsp" style=""></span>bpm&#41; 25&#37; of patients were pacemaker dependent after a follow-up of 45 months&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> However&#44; in other ATTRv series&#44; pacemaker implantation rate is much lower&#44; so we do not recommend prophylactic implantation&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall">Finally&#44; given that ventricular pacing can lead to ventricular dyssynchrony and worsen cardiac output&#44; some centres opt for the implantation of a cardiac resynchronization device when there is an indication for a pacemaker&#46; Recently&#44; it has been suggested that resynchronization could have a beneficial role in ATTR patients with ventricular pacing &#62;40&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a></p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Ventricular arrhythmias</span><p id="par0340" class="elsevierStylePara elsevierViewall">Although the relationship between CA and ventricular arrhythmias is known&#44; the usefulness of the implantable cardioverter-defibrillator &#40;ICD&#41; implantation is not well established and its implantation in primary prevention is generally not recommended given the high rate of sudden death in patients with pulseless electrical activity&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> In the event of deciding to implant an ICD&#44; the transvenous route is preferable to the subcutaneous ICD option in order to have stimulation capacity&#44; since significant bradycardia seems to precede some cases of sudden death in these patients&#46;</p></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Specific treatment</span><p id="par0345" class="elsevierStylePara elsevierViewall">We are witnessing an increase in the availability of new drugs for ATTR &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; The options that have been shown to be effective so far are aimed at reducing TTR production &#40;liver transplantation and gene silencers&#41; or stabilizing circulating TTR &#40;stabilizers&#41;&#46; Other compounds are under investigation&#44; some of them aimed at eliminating amyloid fibrils&#46; The data from different studies emphasize the importance of initiating targeted treatment as early as possible&#44; in the first stages&#44; when they are most effective&#46;</p><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Liver transplantation</span><p id="par0350" class="elsevierStylePara elsevierViewall">Liver transplantation has been used in patients with ATTRv polyneuropathy&#44; in initial stages&#44; with little heart involvement and not advanced age&#46; In Val50Met&#44; the results have shown benefit in both quality of life and survival&#46; However&#44; data in non-Val50Met patients are worse&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a></p><p id="par0355" class="elsevierStylePara elsevierViewall">Despite transplantation&#44; it is important to note that the disease can continue to progress due to native TTR deposition in those organs or systems with previous mutant TTR deposition&#44; not knowing exactly the mechanism by which this phenomenon occurs&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a></p><p id="par0360" class="elsevierStylePara elsevierViewall">The new drugs are effective in stabilizing or suppressing the production of both mutant and native TTR&#44; which is why&#44; in our opinion&#44; liver transplantation in ATTRv is hardly justifiable at the present time&#46;</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Gene silencers</span><p id="par0365" class="elsevierStylePara elsevierViewall">TTR gene silencers &#40;inotersen and patisiran&#41; are capable of reducing the circulating concentration of TTR&#44; stopping&#44; or delaying the progression of the disease&#46; The two compounds have been approved for the treatment of ATTRv neuropathy in stages I and II &#40;walking without assistance or with the aid of a cane&#44; respectively&#41; after demonstrating its efficacy in clinical trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">53&#44;54</span></a> In addition&#44; in the subpopulation of ATTRv with cardiac involvement&#44; patisiran showed benefit in the secondary analysis of biomarkers and echocardiographic parameters with a reduction in mean ventricular thickness&#44; improvement in overall longitudinal <span class="elsevierStyleItalic">strain</span> as well as an increase in cardiac output at 18 months&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">53&#44;55</span></a></p><p id="par0370" class="elsevierStylePara elsevierViewall">Phase III studies are currently underway specifically in patients with ATTRv and ATTRwt CA with patisiran and with a new generation of gene silencers &#40;vutrisiran and AKCEA-TTR-LRx&#41;&#44; which will give a definitive answer about the role of gene silencers in ATTR-CA&#46;</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">TTR stabilizers</span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Tafamidis</span><p id="par0375" class="elsevierStylePara elsevierViewall">This oral compound binds to the place where thyroxine binds to the TTR tetramer&#44; preventing its degradation to dimers and therefore preventing the initiation of the amyloidogenic cascade&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> It was approved by the European Medicines Agency &#40;EMA&#41; in 2011 for stage I ATTRv polyneuropathy in the dose of 20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> It is&#44; so far&#44; the only therapy that has demonstrated effectiveness in TTR CA in a randomized study&#46; Patients with histologically confirmed ATTRv or ATTRwt CA and HF in NYHA I&#8211;III were included&#44; randomized to receive tafamidis 20<span class="elsevierStyleHsp" style=""></span>mg&#44; tafamidis 80<span class="elsevierStyleHsp" style=""></span>mg or placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> After 30 months of follow-up&#44; a 30&#37; reduction in both all-cause mortality and cardiovascular admissions was observed in the treatment group&#44; as well as lower quality of life deterioration&#44; with the benefit being greater in patients in NYHA I and II&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> Subsequent and preliminary data have supported the use of tafamidis at the highest doses&#44; therefore EMA and other regulatory agencies have approved the use of tafamidis free acid 61<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;equivalent to tafamidis meglumine 80<span class="elsevierStyleHsp" style=""></span>mg administered in the trial&#41; for ATTR-CA&#46; Despite the favourable results&#44; its cost-effectiveness has been questioned due to the high price of the drug in the USA<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> and more studies will be needed to evaluate this in Europe&#46;</p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Diflunisal</span><p id="par0380" class="elsevierStylePara elsevierViewall">Diflunisal is a non-steroidal anti-inflammatory drug with the ability to stabilize TTR <span class="elsevierStyleItalic">in vitro</span>&#46; In a randomized study in ATTRv&#44; this compound at doses of 250<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h was shown to delay neurological progression and improve quality of life&#44; without reaching statistical significance in terms of echocardiographic parameters in patients with cardiac involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a> Despite favourable cardiac outcomes in small single-center cohorts&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> its nature as an anti-inflammatory agent makes it&#44; <span class="elsevierStyleItalic">a priori</span>&#44; an unattractive drug for patients with HF due to ATTR-CA&#44; requiring special attention to renal function&#44; the possibility of water retention and the occurrence of complications in anticoagulated patients&#46; In Spain&#44; it can be requested as a foreign drug for selected cases&#44; under close control&#46;</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">AG10 &#40;Acoramidis&#41;</span><p id="par0385" class="elsevierStylePara elsevierViewall">AG10-Acoramidis is the last of the TTR stabilizers in development&#46; So far&#44; the results of phase I and II trials have demonstrated an adequate safety profile&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a> A phase III study is underway to evaluate the safety and efficacy of AG10-Acoramidis in patients with ATTR-CA and HF&#46;</p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Others</span><p id="par0390" class="elsevierStylePara elsevierViewall">There are other molecules under investigation with the aim of accelerating clearance and eliminating existing cardiac depositions&#46; The combination of doxycycline and tauroursodeoxycholic bile acid &#40;TUDCA&#41; has been studied in phase II trials&#44; with variable results and a negative side effect profile as it required the discontinuation of the drug in a significant number of patients&#44; mainly due to skin toxicity and gastrointestinal discomfort&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> There is currently a phase <span class="elsevierStyleSmallCaps">iii</span> trial is currently underway to evaluate this combination in ATTR-CA&#46;</p><p id="par0395" class="elsevierStylePara elsevierViewall">Finally&#44; there are also other early-stage studies with monoclonal antibodies that promote deposition clearance&#46;</p></span></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Future considerations</span><p id="par0400" class="elsevierStylePara elsevierViewall">Due to the intense development in the field&#44; we will soon be faced with several aspects requiring attention&#46; On the one hand&#44; the choice between different specific treatment options without trials that directly compare the drugs with each other&#46; On the other hand&#44; more data are required to be able to establish non-response criteria from a cardiac perspective&#44; determining when to discontinue a specific treatment and consider switching&#46; Finally&#44; another of the still unresolved questions is the effectiveness of drugs administered in combination&#46;</p></span></span><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Funding</span><p id="par0405" class="elsevierStylePara elsevierViewall">This work has been carried out thanks to funding from the <span class="elsevierStyleGrantSponsor" id="gs0005">Instituto de Salud Carlos III</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0005">PI18&#47;00765</span> and <span class="elsevierStyleGrantNumber" refid="gs0005">PI20&#47;01379</span>&#41;&#46;</p></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Conflict of interests</span><p id="par0410" class="elsevierStylePara elsevierViewall">PGP has received fees for lectures and&#47;or advisory activity from Akcea&#174;&#44; Alnylam&#174;&#44; Eidos&#174;&#44; Neuroimmune&#174; and Pfizer&#174;&#46; FD has received fees from Pfizer&#174; for lectures&#46; EGL has received fees for lectures and advisory activity from Pfizer&#174;&#44; Akcea&#174; and Proclara&#174;&#46; The site of PGP&#44; FD and EGL has received research and&#47;or training funding from Akcea&#174;&#44; Alnylam&#174;&#44; Eidos&#174;&#44; Pfizer&#174; and Prothena&#174;&#46;</p></span></span>"
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          "titulo" => "Transthyretin amyloid cardiomyopathy"
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        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Non-hereditary TTR amyloidosis"
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          "titulo" => "Hereditary TTR amyloidosis"
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              "titulo" => "Cardiac manifestations"
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              "titulo" => "Hypertrophic cardiomyopathy phenocopy"
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              "titulo" => "Atrial fibrillation"
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              "titulo" => "Ventricular arrhythmias"
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              "titulo" => "Liver transplantation"
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              "titulo" => "TTR stabilizers"
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                  "titulo" => "Tafamidis"
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                1 => array:2 [
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                  "titulo" => "Diflunisal"
                ]
                2 => array:2 [
                  "identificador" => "sec0150"
                  "titulo" => "AG10 &#40;Acoramidis&#41;"
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                  "titulo" => "Others"
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              "titulo" => "Future considerations"
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          "titulo" => "Funding"
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          "titulo" => "Acknowledgments"
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          "titulo" => "References"
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    "fechaRecibido" => "2020-04-16"
    "fechaAceptado" => "2020-06-27"
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          "clase" => "keyword"
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          "palabras" => array:5 [
            0 => "Amyloidosis"
            1 => "Cardiac amyloidosis"
            2 => "Transthyretin"
            3 => "Heart failure"
            4 => "Treatment"
          ]
        ]
      ]
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1331492"
          "palabras" => array:5 [
            0 => "Amiloidosis"
            1 => "Amiloidosis card&#237;aca"
            2 => "Transtiretina"
            3 => "Insuficiencia card&#237;aca"
            4 => "Tratamiento"
          ]
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Transthyretin &#40;TTR&#41; cardiac amyloidosis is a severe&#44; progressive&#44; infiltrative disease caused by the deposition of TTR at cardiac level&#46; It may be due to a genetic alteration in its hereditary form &#40;ATTRv&#41; or as a consequence of an age-related degenerative process &#40;ATTRwt&#41;&#46; Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis&#44; we now know that ATTR is more frequent than traditionally considered and that it is particularly relevant in patients over 65 years with heart failure or with aortic stenosis&#46; With the appearance of several treatment options capable of modifying the natural history of ATTR&#44; it is necessary for clinicians to be familiar with the diagnostic process and treatment of this disease&#46; This review will cover the clinical spectrum of presentation of ATTR&#44; its diagnosis and treatment&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La amiloidosis card&#237;aca por transtiretina &#40;TTR&#41; es una enfermedad infiltrativa&#44; grave y progresiva&#44; que se produce por el dep&#243;sito de TTR en el coraz&#243;n&#46; Puede deberse a una alteraci&#243;n gen&#233;tica en su forma hereditaria &#40;ATTRv&#41; o a consecuencia de un proceso degenerativo asociado a la edad &#40;ATTRwt&#41;&#46; Gracias a los avances en t&#233;cnicas de imagen y a la posibilidad de realizar un diagn&#243;stico no invasivo hoy conocemos que la ATTR es una enfermedad m&#225;s frecuente de lo tradicionalmente considerado y que es particularmente relevante en pacientes mayores de 65 a&#241;os con insuficiencia card&#237;aca o con estenosis a&#243;rtica&#46; Con la aparici&#243;n de opciones de tratamiento capaces de modificar la historia natural de la ATTR se hace necesario que los cl&#237;nicos est&#233;n familiarizados con el proceso diagn&#243;stico y el tratamiento de esta enfermedad&#46; En esta revisi&#243;n se repasar&#225; el espectro cl&#237;nico de presentaci&#243;n de la ATTR&#44; su diagn&#243;stico y su tratamiento&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Garcia-Pavia P&#44; Dom&#237;nguez F&#44; Gonzalez-Lopez E&#46; Amiloidosis card&#237;aca por transtiretina&#46; Med Clin &#40;Barc&#41;&#46; 2021&#59;156&#58;126&#8211;134&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ATTRwt&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ATTRv&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not known&#46; Quite common&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Low prevalence &#40;&#60;1&#47;100&#44;000&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#37; of HFpEF and LVH<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>60 years of age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Val50Met&#58; 1&#47;538 in endemic area&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#37;&#8211;16&#37; aortic stenosis in the elderly&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Val142Ile&#58; 3&#46;4&#37; of black individuals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Absence of mutations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Point mutation in TTR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hereditary&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-hereditary&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Autosomal dominant &#40;50&#37; in offspring&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Typical presentation age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;60 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Variable according to mutation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male predominance &#40;80&#37; of cases&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male predominance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiac involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Constant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Variable according to mutation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiac manifestations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Heart failure &#40;53&#37;&#8211;86&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Conduction disorders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Conduction disorders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Atrial fibrillation &#40;43&#37;&#8211;67&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Atrial fibrillation &#40;10&#37;&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Degenerative aortic stenosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Extra-cardiac manifestations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Carpal tunnel syndrome &#40;33&#37;&#8211;49&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Bilateral sensory-motor polyneuropathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Lumbar canal stenosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Dysautonomia&#58; orthostatic hypotension&#44; erectile dysfunction&#44; gastrointestinal symptoms&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Atraumatic rupture of the biceps tendon &#40;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Ocular involvement&#58; glaucoma&#44; intravitreal depositions&#44; &#8220;scalloped pupil&#8221;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Sensorineural deafness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ECG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Pseudoinfarction pattern &#40;63&#37;&#8211;66&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Pseudoinfarction pattern &#40;18&#37;&#8211;69&#37;&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Low voltage &#40;22&#37;&#8211;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Low voltage &#40;2&#37;&#8211;25&#37;&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Ventricular hypertrophy according to Sokolow &#40;6&#37;&#8211;13&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Ventricular hypertrophy according to Sokolow &#40;3&#37;&#8211;8&#37;&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Echocardiogram&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Moderate-severe hypertrophy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Moderate hypertrophy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Mild-moderately reduced LVEF &#40;30&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- LVEF usually preserved&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiac MRI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Global or transmural subendocardial delayed enhancement&#46; Elevation of native T1 and ECV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bone scintigraphy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Perugini grades 2&#8211;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Perugini grade 0&#58; asymptomatic carrier&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Perugini grade 1&#58; incipient cardiac involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Perugini grades 2&#8211;3&#58; cardiac involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Average survival after diagnosis&#44; without treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8764;3&#46;5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Variable according to mutation&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8764;2&#46;5 years in Val142Ile&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2514269.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Comparison of the characteristics of hereditary transthyretin amyloidosis &#40;ATTRv&#41; and non-hereditary o <span class="elsevierStyleItalic">wild-type</span> &#40;ATTRwt&#41;&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Left ventricular hypertrophy &#8805;12&#8239;mm and one of the following&#58;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical scenarios&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Heart failure &#8805;65 years of age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aortic stenosis &#8805;65 years of age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="11" align="left" valign="middle">Clinical data</td><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypotension if previous arterial hypertension or need to reduce antihypertensive treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dysautonomia&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Significant orthostatic hypotension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Erectile dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Alternating diarrhoea-constipation and unjustified weight loss&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Peripheral neuropathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Skin ecchymosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bilateral carpal tunnel syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atraumatic rupture of the biceps tendon &#40;&#8220;Popeye&#8217;s sign&#8221;&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lumbar canal stenosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Possible family history&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="middle">ECG data</td><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pseudoinfarction pattern on ECG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Discrepancy of QRS voltages&#47;ventricular hypertrophy echocardiogram&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Conduction disorders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="5" align="left" valign="middle">Echocardiogram</td><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Right ventricular hypertrophy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atrioventricular valve and interatrial septum thickening&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Low-velocity signals in tissue <span class="elsevierStyleItalic">doppler</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pericardial effusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction of global longitudinal <span class="elsevierStyleItalic">strain</span> with preservation of apical values&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="middle">Cardiac MRI</td><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Global or transmural subendocardial delayed enhancement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increase in native T1 and extracellular volume&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2514271.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Clinical scenarios and signs of suspicion that together with left ventricular hypertrophy should lead to consideration of transthyretin amyloidosis&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0025"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Scenario&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">How to suspect and detect it&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Possible false positives</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AL amyloidosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Abnormalities in serum light chains and&#47;or in serum or urine immunofixation&#46; Requires histological confirmation with typing through immunohistochemistry or mass spectrometry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hydroxychloroquine toxicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">History-taking and medical records&#46; Requires histological confirmation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ApoAI&#44; ApoAII and ApoAIV amyloidosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Concomitant renal failure&#46; Requires genetic study&#47;histological confirmation with typing through mass spectrometry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ApoA<span class="elsevierStyleSmallCaps">IV</span> amyloidosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Concomitant renal failure&#46; Requires histological confirmation with typing through mass spectrometry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B2-microglobulin amyloidosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal failure with dialysis for a long time&#46; Requires histological confirmation with typing through mass spectrometry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Blood pool</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systolic dysfunction&#46; Use SPECT to detect ventricular wall uptake&#46; Lengthen acquisition time interval&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rib fractures&#44; valvular&#47;annular calcifications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">History-taking&#46; Use SPECT to detect ventricular wall uptake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recent myocardial infarction &#40;&#60;4 weeks&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">History-taking and medical records&#46; Use SPECT to detect global myocardial uptake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Possible false negatives</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ATTRv Phe84Leu&#44; ATTRv Ser97Tyr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Concomitant neuropathy&#46; Family history&#46; Genetic study of TTR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Very mild involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Requires histological confirmation by biopsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Delayed acquisition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shorten acquisition time interval&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2514272.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">False positives and negatives in diphosphonate scintigraphy in the diagnosis of transthyretin amyloidosis&#46;</p>"
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        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0030"
            "detalle" => "Table "
            "rol" => "short"
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        ]
        "tabla" => array:1 [
          "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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Supportive treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Low sodium diet &#40;&#60;2<span class="elsevierStyleHsp" style=""></span>g&#47;day&#41;&#44; daily weight&#44; water restriction &#40;&#8804;1&#46;5<span class="elsevierStyleHsp" style=""></span>L&#47;day&#41; and diuretics&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Avoid ACEI and AIIRA&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Avoid beta blockers&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Contraindicated dihydropyridine calcium antagonists&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Relative contraindication for digoxin&#46; Use at low doses and with close monitoring&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Advanced heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Heart transplantation in selected cases&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Unclear role of ventricular assistance devices&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atrial fibrillation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Individualize rate control or rhythm control&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Amiodarone as the antiarrhythmic of choice&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- ECV as a high-risk procedure&#46; TEE always before ECV&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Thromboembolic risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Anticoagulation in AF&#44; regardless of CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>VASc&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Consider anticoagulation in SR in selected cases if there is atrial dysfunction&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Conduction disorders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Pacemaker implantation according to standard indications&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Assess CRT if there is a high predicted ventricular pacing rate &#40;&#62;40&#37;&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ventricular arrhythmias&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- ICD implantation in secondary prevention&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- ICD in primary prevention not recommended&#46; Individualize indication&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Specific treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ATTRwt&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Tafamidis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Diflunisal <span class="elsevierStyleItalic">off-label&#46;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">TTRv with cardiac involvement without neuropathy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">- Tafamidis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">- Diflunisal <span class="elsevierStyleItalic">off-label&#46;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ATTRv with cardiac involvement with neuropathy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">- Tafamidis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Patisiran&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Inotersen&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  """
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Supportive and specific treatment of transthyretin CA&#46;</p>"
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        0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Amiloidosis&#46; Tambi&#233;n una enfermedad del coraz&#243;n"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
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                      "Revista" => array:6 [
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                            "web" => "Medline"
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                      "autores" => array:1 [
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                          "etal" => false
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                            1 => "P&#46; Elliott"
                            2 => "R&#46; Comenzo"
                            3 => "M&#46; Semigran"
                            4 => "C&#46; Rapezzi"
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                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.116.024438"
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                  "contribucion" => array:1 [
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                      "titulo" => "Amyloid nomenclature 2018&#58; recommendations by the International Society of Amyloidosis &#40;ISA&#41; nomenclature committee"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            3 => "G&#46; Merlini"
                            4 => "M&#46;J&#46;M&#46; Saraiva"
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                      "titulo" => "Diagnosis and treatment of transthyretin cardiac amyloidosis&#46; Progress and hope"
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                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Esp Cardiol &#40;Engl Ed&#41;"
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                            0 => "L&#46; Mohamed-Salem"
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