Case report
Severe heart disease in an unusual case of familial amyloid polyneuropathy type I
Doença cardíaca grave numa situação invulgar de polineuropatia amiloidótica familiar tipo-I
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Pacemaker electrode (E), right atrium (F) and left atrium (G).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Manuel Barreiro, Cecília Corros, Laura García, Alfredo Renilla, María Martin, Ana García" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Manuel" "apellidos" => "Barreiro" ] 1 => array:2 [ "nombre" => "Cecília" "apellidos" => "Corros" ] 2 => array:2 [ "nombre" => "Laura" "apellidos" => "García" ] 3 => array:2 [ "nombre" => "Alfredo" "apellidos" => "Renilla" ] 4 => array:2 [ "nombre" => "María" "apellidos" => "Martin" ] 5 => array:2 [ "nombre" => "Ana" "apellidos" => "García" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217420491300250X?idApp=UINPBA00004E" "url" => "/21742049/0000003200000009/v1_201312060118/S217420491300250X/v1_201312060118/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S2174204913001748" "issn" => "21742049" "doi" => "10.1016/j.repce.2013.10.010" "estado" => 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=> true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1247 "Ancho" => 995 "Tamanyo" => 112058 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Chest X-ray (A) and transthoracic echocardiography (B) at admission.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Luís Ferreira dos Santos, Davide Moreira, Pedro Ribeiro, Bruno Rodrigues, Emanuel Correia, Luís Nunes, Miguel Sequeira, Ana Albuquerque, Inês Barros, José Pedro Saraiva, Oliveira Santos" "autores" => array:11 [ 0 => array:2 [ "nombre" => "Luís" "apellidos" => "Ferreira dos Santos" ] 1 => array:2 [ "nombre" => "Davide" "apellidos" => 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"https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255113001674?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204913001748?idApp=UINPBA00004E" "url" => "/21742049/0000003200000009/v1_201312060118/S2174204913001748/v1_201312060118/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case report</span>" "titulo" => "Severe heart disease in an unusual case of familial amyloid polyneuropathy type I" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "729" "paginaFinal" => "733" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Miguel Oliveira Santos, Dulce Brito" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Miguel" "apellidos" => "Oliveira Santos" "email" => array:1 [ 0 => "migueloliveirasantos@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Dulce" "apellidos" => "Brito" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Faculdade de Medicina da Universidade de Lisboa, Centro de Cardiologia da Universidade de Lisboa (CCUL), Lisboa, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Serviço de Cardiologia I, Centro Hospitalar de Lisboa Norte, E.P.E., Lisboa, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Doença cardíaca grave numa situação invulgar de polineuropatia amiloidótica familiar tipo-I" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 720 "Ancho" => 3335 "Tamanyo" => 386686 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Echocardiographic findings at age 66. M-mode revealed a dilated left atrium (56 mm) (A), an enlarged left ventricular cavity (58.47 mm) with wall thickening (15.11 mm) and a small pericardial effusion (B). Doppler showed diastolic transmitral flow with an E/A-wave ratio of 2.39 and a deceleration time of 147 ms (C).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Case report</span><p id="par0005" class="elsevierStylePara elsevierViewall">A 66-year-old white woman from Lisbon (Portugal) was being followed in the neurology department due to progressive sensorimotor and autonomic polyneuropathy of 12 years’ duration. Physical examination showed tetraparesis, thermal hypoesthesia and distal muscle atrophy of the lower limbs. Patellar and Achilles tendon reflexes were abolished. Electromyography revealed severe axonal sensorimotor polyneuropathy.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The most common diagnoses of polyneuropathy were excluded. A fat biopsy showed amyloid deposits. Genetic testing was performed and the Val30Met mutation in the transthyretin (<span class="elsevierStyleItalic">TTR</span>) gene was identified in heterozygosity.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The suspicion of amyloid cardiomyopathy had emerged at age 60, when the patient underwent transthoracic echocardiography (echo) during investigation of anginal pain. The echo findings suggestive of amyloid infiltration included an E/A-wave ratio of 0.6 (Doppler mitral inflow), left atrial (LA) dilatation (end-systolic diameter of 50 mm), mitral-aortic valvular thickening and a small pericardial effusion. Left ventricular (LV) dimensions were normal (50 mm in late diastole), with no hypertrophy and preserved systolic function.</p><p id="par0020" class="elsevierStylePara elsevierViewall">One year later, in order to clarify episodes of syncope and dizziness, 24-hour ambulatory electrocardiographic (Holter) monitoring was performed. Supraventricular premature extrasystoles with compensatory pauses of up to 2.5 s were detected. Four months later, sinoatrial block (with some pauses longer than 4 s) was also identified on Holter.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Due to symptomatic bradyarrhythmia a dual-chamber pacing system (DDDR mode) was implanted, and the patient remained asymptomatic for the next five years.</p><p id="par0030" class="elsevierStylePara elsevierViewall">At the age of 66, she was admitted to the cardiology department in heart failure (HF), NYHA class III. Physical examination revealed atrial fibrillation (AF) with a controlled ventricular rate and anasarca (total weight of 100 kg for a calculated ideal dry weight of about 60 kg). The echo examination showed LV wall thickening (15.11 mm), an enlarged LV cavity (58.47 mm at end-diastole), greater LA dilatation (56 mm) and diastolic transmitral flow with an almost restrictive pattern, with an E/A-wave ratio of 2.39 and deceleration time of 147 ms (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). Mild to moderate mitral regurgitation was also observed. Mild thickening of the aortic and mitral valves persisted as well as the small pericardial effusion, both findings observed six years previously.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The patient's anasarca (also associated with nephrotic proteinuria and hypoalbuminemia) improved slightly with intravenous administration of albumin plus diuretics, but hemodialysis was needed. She lost 40 kg of body fluids and was transferred to the nephrology department.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The patient had mild and well-controlled systemic hypertension. There was no known family history of FAP type I. Both her parents had died of malignant disease at unknown ages. She has a daughter and a son, both healthy adults.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discussion</span><p id="par0045" class="elsevierStylePara elsevierViewall">The term “amyloidosis” covers a heterogeneous group of rare diseases (acquired or inherited) characterized by extracellular deposition of abnormal insoluble fibrils resulting from protein misfolding.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> Accumulation of amyloid deposits in various tissues impairs their structure and function.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Currently, there are 27 different types of amyloidosis classified according to their precursor protein.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> They may also be classified as systemic or local based on organ involvement.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">A definitive diagnosis of amyloidosis is usually made by biopsy specimen, in which Congo red staining reveals a typical red color under microscopy and apple-green birefringence under polarized light.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3,6</span></a> But determination of the amyloid type is only possible by immunohistochemical techniques.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The heart is usually affected, as part of systemic involvement.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The most common systemic amyloidoses with myocardial involvement are acquired monoclonal immunoglobulin light-chain amyloidosis and TTR-related forms.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> Under the broad designation of amyloidosis, there are several clinically distinct entities that also require different treatment.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> But the severity of cardiac involvement in all forms is an important prognostic factor and early diagnosis remains a challenge.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">FAP type I is a rare autosomal dominant systemic amyloidosis caused by the Val30Met mutation in the <span class="elsevierStyleItalic">TTR</span> gene.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8–11</span></a> It was first described by Corindo de Andrade, a Portuguese neurologist, in 1952.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Higher prevalences in endemic areas of Portugal, Japan and Sweden have been reported.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> TTR is a plasma protein synthesized mainly in the liver and to a lesser extent in the choroid plexus and ocular tissues.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,12,13</span></a> It acts as a carrier for thyroxine and retinol-binding protein.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,13</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">A wide phenotypic heterogeneity has been found in FAP type I and is influenced by several factors such as genetic status (homozygosity or heterozygosity and penetrance), geographic distribution, age of onset and clinical spectrum.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,12,14</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In Portugal, early-onset cases, usually before the age of 40, are more common than late-onset cases, which are rare and tend to occur in non-endemic areas.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,14</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Symptomatic disease usually evolves over 10–20 years.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Rapidly progressive sensorimotor polyneuropathy, which may be associated with dysautonomia, usually characterizes the initial clinical picture.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a> Other clinical manifestations of cardiac, renal, ocular and gastrointestinal involvement often appear later.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Cardiac involvement is common in hereditary TTR amyloidosis, but its clinical expression and severity depend on the amyloidogenic TTR variant.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,16</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">FAP type I is mostly linked with dysrhythmias and cardiac conduction disturbances.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15–19</span></a> Amyloid infiltration into the subendocardium is probably the pathophysiological mechanism.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19,20</span></a> Moreover, dysautonomia may also contribute to these disturbances, leading to sudden cardiac death (SCD).<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a> Cardiac conduction system involvement may result in sinus node dysfunction and atrioventricular and intraventricular block.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19–21</span></a> Sinoatrial and/or atrioventricular block associated with Stokes–Adams syndrome requires pacemaker implantation<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,19,22</span></a> as soon as possible, in order to alleviate symptoms and possibly prevent SCD.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Supraventricular dysrhythmias associated with interventricular septum (IVS) thickening and LA dilatation have been reported.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In patients aged over 60 a relationship between ventricular late potentials, non-sustained ventricular dysrhythmias and increased LV wall thickening has also been described.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Besides autonomic dysfunction,<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23–25</span></a> ventricular dyssynchrony appears to be another mechanism responsible for the reduced heart rate variability observed in FAP type I, as it correlates with shorter LV filling time and prolonged total isovolumic time, regardless of QRS width.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">There are some reports of patients suffering hemodynamic instability and severe hypotension during anesthesia, particularly with acetylcholine-like anesthetics, due to the effects of dysautonomia on self-regulatory blood pressure mechanisms.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25–27</span></a> This may be related to a discrepancy between cardiac muscarinic receptors and cardiac beta<span class="elsevierStyleInf">1</span>-receptor regulation. Circulating catecholamines produced by the adrenal medulla maintain beta<span class="elsevierStyleInf">1</span>-receptor sensitivity, while upregulation of muscarinic receptors may be due to lack of cholinergic neurostimulation.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Amyloid cardiomyopathy with HF is an uncommon presentation in FAP type I.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,18,21</span></a> A strong relationship between age of onset, IVS thickness and LA dimension has been observed.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Cardiomyopathy with mild LV thickening (>12 mm but below the usual value considered diagnostic for LV hypertrophy) may appear prior to the onset of polyneuropathy.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Electrocardiography (ECG) and echo have an important role in the diagnosis of amyloid heart disease. Only a third of FAP type I patients show low-voltage QRS complexes due to amyloid infiltration.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Dysrhythmias and conduction disturbances are frequently identified. Amyloid cardiomyopathy may be demonstrated when there is IVS end-diastolic thickness >12 mm on echo, after excluding other more probable causes.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Echo findings other than LV wall thickening (with a granular sparkling appearance of the IVS) are a non-enlarged LV cavity, diastolic dysfunction, atrial septal thickening, atrial dilatation, valvular thickening and small pericardial effusion.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,7,29</span></a> In contrast to other types, echo signs in FAP type I are subtle.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Early diagnosis of cardiac amyloidosis is of great value since it determines therapy and prognosis. But ECG and echo alone or in combination have low diagnostic accuracy for early detection of cardiac involvement. Moreover, only combining the findings of the two techniques (low-voltage QRS complexes and IVS thickening >19.8 mm) enables a diagnosis of cardiac amyloidosis to be made with a sensitivity of 72% and specificity of 92%.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Other echo techniques (such as tissue Doppler and strain),<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a><span class="elsevierStyleSup">99m</span>Tc-DPD scintigraphy<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>, <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> and serum NT-proBNP assay<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> have shown promising results in detecting early signs of cardiac amyloid infiltration before the development of clinical manifestations and even abnormal echo findings on standard examination.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Liver transplantation is established as a therapeutic option to prevent disease progression because it suppresses pathological TTR production.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32–34</span></a> Nevertheless, development and/or worsening of dysrhythmias and cardiac conduction disturbances,<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32,35</span></a> cardiac dysautonomia<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> and amyloid cardiomyopathy<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> have been reported after liver transplantation. Constant deposition of wild-type TTR preferentially on pre-existing cardiac amyloid deposits after liver transplantation has been suggested as a plausible mechanism.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34,37</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Myocardial involvement in FAP type I thus carries a poor prognosis even after liver transplantation, and new treatments that offer better control of heart disease are therefore needed. Recently, the new drug tafamidis, which stabilizes the native homotetramer, preventing the formation of cytotoxic species, has been approved by the European Medical Association for treatment of stage 1 FAP type I.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> However, its benefit in cardiac amyloidosis is not yet known. Clinical trials of experimental drugs that block the amyloidogenic process in several ways, such as resveratrol and its analogs,<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> carvedilol,<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> doxycycline<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> and ribozymes<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> have shown promising results for future treatment of cardiac involvement in FAP type I.</p><p id="par0135" class="elsevierStylePara elsevierViewall">The case reported here has some unusual aspects. Our patient had late onset FAP type I (the clinical picture emerged after the age of 50). This is unusual in Portugal, although similar cases outside the endemic areas have been reported. However, the lack of information on the patient's genealogy means that no conclusions can be drawn.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Although the patient had no known family history of FAP type I, genetic testing confirmed the presence of the Val30Met mutation in the <span class="elsevierStyleItalic">TTR</span> gene. Her parents died without undergoing genetic screening, so three hypotheses may be considered. First, given the condition's phenotypic variability, her parents may have died prior to the clinical onset of the disease. If this was the case, they may also have had late-onset disease. Second, the parents may also have been asymptomatic owing to gonadal mosaicism. And third, a <span class="elsevierStyleItalic">de novo</span> mutation may have occurred in our patient.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The patient had sinoatrial block and AF, which are frequent complications of cardiac involvement. Stokes–Adams syndrome related to sinoatrial block was treated successfully with pacemaker implantation. Nevertheless the severity of amyloid cardiomyopathy as denoted by echo findings – including significant LV wall thickening and changes over time in Doppler mitral inflow pattern – is not typical in this type of amyloidosis. The same is true for the clinical severity of HF, which seems to be associated with amyloid cardiomyopathy and significant diastolic dysfunction. The patient's anasarca may be explained by a maladaptive response to congestive low-output HF as well as by nephrotic syndrome associated with renal amyloid infiltration.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusions</span><p id="par0150" class="elsevierStylePara elsevierViewall">The condition's phenotypic heterogeneity, as well as the absence of a known family history, should be considered when FAP type I is a diagnostic hypothesis. This helps to avoid late and inaccurate diagnosis and enables counseling of the family with regard to genetic screening.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Symptomatic improvement and prevention of possible SCD can be achieved in patients with bradyarrhythmias by early pacemaker implantation.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Advances in diagnostic techniques that will allow detection of early signs of amyloid heart disease, together with the development of new therapies, are urgently needed to reduce mortality related to cardiac events in FAP type I patients and to offer them a better quality of life.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Due to its multisystemic nature, patients with FAP type I should be referred to specialized centers capable of providing a multidisciplinary approach.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ethical disclosures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Protection of human and animal subjects</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Confidentiality of data</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Right to privacy and informed consent</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of interest</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres296959" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec280623" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres296958" "titulo" => "Resumo" ] 3 => array:2 [ "identificador" => "xpalclavsec280624" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Case report" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Conclusions" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-09-01" "fechaAceptado" => "2013-02-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec280623" "palabras" => array:5 [ 0 => "Familial amyloid polyneuropathy type I" 1 => "Dysrhythmia" 2 => "Conduction disturbances" 3 => "Cardiomyopathy" 4 => "Dysautonomia" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec280624" "palabras" => array:5 [ 0 => "Polineuropatia amiloidótica familiar tipo-I" 1 => "Disritmia" 2 => "Perturbações da condução" 3 => "Miocardiopatia" 4 => "Disautonomia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Familial amyloid polyneuropathy type I (FAP type I) is a rare hereditary systemic amyloidosis caused by the Val30Met mutation in the transthyretin (<span class="elsevierStyleItalic">TTR</span>) gene. The clinical onset and spectrum are variable and depend on phenotypic heterogeneity. Cardiac complications (dysrhythmias and conduction disturbances, cardiomyopathy and dysautonomia) indicate a poor prognosis, even after liver transplantation. We report an atypical case of FAP type I, highlighting the severe cardiac involvement and its complications.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Early diagnosis of amyloid heart disease is increasingly important in the context of several clinical trials of promising new and experimental drugs.</p>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A polineuropatia amiloidótica familiar tipo-I (PAF tipo-I) é um tipo raro de amiloidose hereditária e sistémica causada pela mutação Val30Met no gene da transtirretina (TTR). O início das manifestações e o espectro clínico podem ser variáveis e dependem da heterogeneidade fenotípica. As complicações cardíacas (disritmias e perturbações da condução, miocardiopatia e disautonomia) ditam um prognóstico mais reservado, mesmo após transplante hepático. É descrito um caso clínico atípico de PAF tipo-I com ênfase no grave envolvimento cardíaco e nas suas complicações.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">O diagnóstico precoce de cardiopatia amiloidótica tem assumido relevância no âmbito de vários ensaios clínicos com fármacos experimentais promissores.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Oliveira Santos M, Brito D. Doença cardíaca grave numa situação invulgar de polineuropatia amiloidótica familiar tipo-I 2012. http://dx.doi.org/.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 720 "Ancho" => 3335 "Tamanyo" => 386686 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Echocardiographic findings at age 66. M-mode revealed a dilated left atrium (56 mm) (A), an enlarged left ventricular cavity (58.47 mm) with wall thickening (15.11 mm) and a small pericardial effusion (B). Doppler showed diastolic transmitral flow with an E/A-wave ratio of 2.39 and a deceleration time of 147 ms (C).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:42 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Amyloidosis—recent developments" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T. Pettersson" 1 => "Y.T. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 3 | 12 |
| 2024 October | 51 | 33 | 84 |
| 2024 September | 47 | 22 | 69 |
| 2024 August | 42 | 33 | 75 |
| 2024 July | 31 | 26 | 57 |
| 2024 June | 38 | 16 | 54 |
| 2024 May | 37 | 23 | 60 |
| 2024 April | 36 | 25 | 61 |
| 2024 March | 30 | 18 | 48 |
| 2024 February | 23 | 26 | 49 |
| 2024 January | 33 | 28 | 61 |
| 2023 December | 28 | 20 | 48 |
| 2023 November | 32 | 24 | 56 |
| 2023 October | 27 | 17 | 44 |
| 2023 September | 20 | 21 | 41 |
| 2023 August | 24 | 21 | 45 |
| 2023 July | 28 | 8 | 36 |
| 2023 June | 19 | 12 | 31 |
| 2023 May | 38 | 30 | 68 |
| 2023 April | 22 | 6 | 28 |
| 2023 March | 42 | 24 | 66 |
| 2023 February | 43 | 22 | 65 |
| 2023 January | 27 | 19 | 46 |
| 2022 December | 46 | 15 | 61 |
| 2022 November | 79 | 30 | 109 |
| 2022 October | 40 | 16 | 56 |
| 2022 September | 40 | 38 | 78 |
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| 2022 July | 46 | 23 | 69 |
| 2022 June | 46 | 20 | 66 |
| 2022 May | 38 | 33 | 71 |
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| 2021 December | 21 | 29 | 50 |
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| 2021 May | 41 | 30 | 71 |
| 2021 April | 50 | 48 | 98 |
| 2021 March | 101 | 19 | 120 |
| 2021 February | 78 | 10 | 88 |
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| 2020 December | 35 | 6 | 41 |
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| 2020 September | 57 | 8 | 65 |
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| 2020 July | 43 | 6 | 49 |
| 2020 June | 42 | 3 | 45 |
| 2020 May | 49 | 10 | 59 |
| 2020 April | 39 | 21 | 60 |
| 2020 March | 43 | 5 | 48 |
| 2020 February | 121 | 25 | 146 |
| 2020 January | 33 | 4 | 37 |
| 2019 December | 25 | 9 | 34 |
| 2019 November | 40 | 6 | 46 |
| 2019 October | 26 | 3 | 29 |
| 2019 September | 32 | 7 | 39 |
| 2019 August | 32 | 5 | 37 |
| 2019 July | 30 | 10 | 40 |
| 2019 June | 35 | 8 | 43 |
| 2019 May | 45 | 16 | 61 |
| 2019 April | 29 | 17 | 46 |
| 2019 March | 32 | 9 | 41 |
| 2019 February | 56 | 12 | 68 |
| 2019 January | 60 | 10 | 70 |
| 2018 December | 114 | 12 | 126 |
| 2018 November | 208 | 6 | 214 |
| 2018 October | 380 | 19 | 399 |
| 2018 September | 71 | 8 | 79 |
| 2018 August | 53 | 6 | 59 |
| 2018 July | 57 | 8 | 65 |
| 2018 June | 110 | 3 | 113 |
| 2018 May | 128 | 6 | 134 |
| 2018 April | 189 | 12 | 201 |
| 2018 March | 270 | 13 | 283 |
| 2018 February | 171 | 4 | 175 |
| 2018 January | 132 | 6 | 138 |
| 2017 December | 227 | 7 | 234 |
| 2017 November | 65 | 7 | 72 |
| 2017 October | 24 | 15 | 39 |
| 2017 September | 29 | 5 | 34 |
| 2017 August | 35 | 10 | 45 |
| 2017 July | 27 | 8 | 35 |
| 2017 June | 35 | 2 | 37 |
| 2017 May | 41 | 10 | 51 |
| 2017 April | 33 | 7 | 40 |
| 2017 March | 34 | 17 | 51 |
| 2017 February | 22 | 3 | 25 |
| 2017 January | 27 | 6 | 33 |
| 2016 December | 35 | 6 | 41 |
| 2016 November | 16 | 2 | 18 |
| 2016 October | 39 | 8 | 47 |
| 2016 September | 17 | 16 | 33 |
| 2016 August | 3 | 2 | 5 |
| 2016 July | 11 | 6 | 17 |
| 2016 June | 4 | 10 | 14 |
| 2016 May | 10 | 4 | 14 |
| 2016 April | 15 | 1 | 16 |
| 2016 March | 36 | 6 | 42 |
| 2016 February | 32 | 11 | 43 |
| 2016 January | 24 | 9 | 33 |
| 2015 December | 34 | 8 | 42 |
| 2015 November | 21 | 4 | 25 |
| 2015 October | 28 | 6 | 34 |
| 2015 September | 28 | 12 | 40 |
| 2015 August | 27 | 4 | 31 |
| 2015 July | 22 | 2 | 24 |
| 2015 June | 11 | 2 | 13 |
| 2015 May | 19 | 4 | 23 |
| 2015 April | 21 | 9 | 30 |
| 2015 March | 14 | 2 | 16 |
| 2015 February | 14 | 2 | 16 |
| 2015 January | 20 | 5 | 25 |
| 2014 December | 24 | 8 | 32 |
| 2014 November | 22 | 2 | 24 |
| 2014 October | 39 | 5 | 44 |
| 2014 September | 26 | 4 | 30 |
| 2014 August | 24 | 5 | 29 |
| 2014 July | 28 | 7 | 35 |
| 2014 June | 22 | 3 | 25 |
| 2014 May | 33 | 15 | 48 |
| 2014 April | 28 | 2 | 30 |
| 2014 March | 41 | 14 | 55 |
| 2014 February | 52 | 10 | 62 |
| 2014 January | 41 | 15 | 56 |
| 2013 December | 27 | 10 | 37 |
Show all
