Edited by: Dr. Juan González Moreno - Hospital Universitario, Spain. Dra. Inés Losada López - Hospital Universitario, Spain
More infoarray:24 [ "pii" => "S2387020624003152" "issn" => "23870206" "doi" => "10.1016/j.medcle.2024.03.007" "estado" => "S300" "fechaPublicacion" => "2024-08-16" "aid" => "6647" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2024" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2024;163:e36-e43" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0025775324002173" "issn" => "00257753" "doi" => "10.1016/j.medcli.2024.03.005" "estado" => "S300" "fechaPublicacion" => "2024-08-16" "aid" => "6647" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Med Clin. 2024;163:e36-e43" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artículo especial</span>" "titulo" => "Actualización en amiloidosis cardiaca por transtiretina <span class="elsevierStyleItalic">wild-type</span>: guía clínica para su diagnóstico y tratamiento" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "e36" "paginaFinal" => "e43" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Update in ‘wild-type’ transthyretin cardiac amyloidosis: Clinical guide for its diagnosis and treatment" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figura 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1570 "Ancho" => 2580 "Tamanyo" => 440739 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Puntos clave sobre la evidencia emergente en el tratamiento de las complicaciones de la amiloidosis cardiaca por transtiretina (ATTR-CA).EA: estenosis aórtica; FA: fibrilación auricular; iSLGT2: inhibidores del cotransportador de sodio glucosa tipo<span class="elsevierStyleHsp" style=""></span>2; MRAs: inhibidores de la aldosterona; TAVI: prótesis aórtica transcatéter.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Lorena Herrador, Sergi Yun, José González-Costello" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Lorena" "apellidos" => "Herrador" ] 1 => array:2 [ "nombre" => "Sergi" "apellidos" => "Yun" ] 2 => array:2 [ "nombre" => "José" "apellidos" => "González-Costello" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020624003152" "doi" => "10.1016/j.medcle.2024.03.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624003152?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775324002173?idApp=UINPBA00004N" "url" => "/00257753/0000016300000003/v1_202408050432/S0025775324002173/v1_202408050432/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020624003127" "issn" => "23870206" "doi" => "10.1016/j.medcle.2024.03.005" "estado" => "S300" "fechaPublicacion" => "2024-08-16" "aid" => "6643" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2024;163:e44-e48" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>" "titulo" => "Artificial intelligence in medicine: Ethical, deontological aspects and the impact on the doctor-patient relationship" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "e44" "paginaFinal" => "e48" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Inteligencia artificial en medicina: aspectos éticos, deontológicos y el impacto en la relación medico-paciente" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Montse Esquerda, Francesc Pifarre-Esquerda" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Montse" "apellidos" => "Esquerda" ] 1 => array:2 [ "nombre" => "Francesc" "apellidos" => "Pifarre-Esquerda" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775324002148" "doi" => "10.1016/j.medcli.2024.03.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775324002148?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624003127?idApp=UINPBA00004N" "url" => "/23870206/0000016300000003/v1_202408230644/S2387020624003127/v1_202408230644/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S2387020624003176" "issn" => "23870206" "doi" => "10.1016/j.medcle.2023.11.043" "estado" => "S300" "fechaPublicacion" => "2024-08-16" "aid" => "6536" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2024;163:e34-e35" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Image in medicine</span>" "titulo" => "Resolution of cardiac involvement with cobimetinib in Erdheim–Chester disease" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "e34" "paginaFinal" => "e35" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Resolución de la afectación cardiaca con cobimetinib en enfermedad de Erdheim-Chester" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:6 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 884 "Ancho" => 1233 "Tamanyo" => 122953 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Silvia Suárez-Díaz, Joaquín Bernardo-Cofiño, José Antonio Fernández-Villameytide, Luis Caminal-Montero" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Silvia" "apellidos" => "Suárez-Díaz" ] 1 => array:2 [ "nombre" => "Joaquín" "apellidos" => "Bernardo-Cofiño" ] 2 => array:2 [ "nombre" => "José Antonio" "apellidos" => "Fernández-Villameytide" ] 3 => array:2 [ "nombre" => "Luis" "apellidos" => "Caminal-Montero" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624003176?idApp=UINPBA00004N" "url" => "/23870206/0000016300000003/v1_202408230644/S2387020624003176/v1_202408230644/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>" "titulo" => "Update in ‘wild-type’ transthyretin cardiac amyloidosis: Clinical guide for its diagnosis and treatment" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "e36" "paginaFinal" => "e43" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Lorena Herrador, Sergi Yun, José González-Costello" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Lorena" "apellidos" => "Herrador" "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" ] ] ] 1 => array:3 [ "nombre" => "Sergi" "apellidos" => "Yun" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 2 => array:4 [ "nombre" => "José" "apellidos" => "González-Costello" "email" => array:1 [ 0 => "jgonzalez@bellvitgehospital.cat" ] "referencia" => array:5 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] 4 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Unidad de Insuficiencia Cardíaca Avanzada y Trasplante Cardíaco, Servicio de Cardiología, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Bio-Heart, grupo de investigación en enfermedades cardiovasculares, Instituto de Investigación Biomédica de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Insuficiencia Cardíaca Comunitaria, Servicio de Medicina Interna, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto Carlos III, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Departamento de Ciencias Clínicas, Facultad de Medicina y Ciencias de la Salud, Universidad de Barcelona, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Actualización en amiloidosis cardiaca por transtiretina <span class="elsevierStyleItalic">wild-type</span>: guía clínica para su diagnóstico y tratamiento" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2069 "Ancho" => 3333 "Tamanyo" => 629296 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Semi-quantitative visual score of pyrophosphate scintigraphy (Perugini score) and diagnostic algorithm for amyloid cardiomyopathy based on the score.</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">AL: light chain amyloidosis; ATTR: transthyretin amyloidosis; ATTRv: hereditary transthyretin amyloidosis; EMB: endomyocardial biopsy.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The term “amyloidosis” covers several diseases characterised by the extracellular deposition (localised or systemic) of unstable soluble proteins which, after undergoing conformational changes, misfolding and aggregation, form insoluble structures called fibrils that cause progressive dysfunction of the affected organs.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The different subtypes of amyloidosis are classified according to the type of protein deposited, with light chain amyloidosis (AL) (a form of haematological malignancy) and transthyretin amyloidosis (ATTR) being the most common, caused by the deposition of a protein produced mainly in the liver and involved in the transport of thyroxine and retinol binding protein. Within the latter, transthyretin wild-type or wild-type (ATTRwt) amyloidosis is the most common. There is also a subgroup of less common amyloidoses that represent around 2% of the total, due to the deposition of other proteins, such as ApoA, AB2M, AFib and AGel, among others.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Epidemiology</span><p id="par0015" class="elsevierStylePara elsevierViewall">Exact data on the overall prevalence of each type of amyloidosis are unknown. The most common is ATTRwt, which currently accounts for 13–20% of patients with heart failure (HF) and ventricular hypertrophy.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A multicentre Spanish registry including HF patients seen in internal medicine departments detected 20.1% amyloidosis in patients over 65 years of age with HF (84.6% ATTR; 2.2% AL, and 13.2% of undetermined cause). 5.2% were hereditary ATTR (ATTRv), although many of them did not undergo genetic testing.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The incidence of the disease is increasing exponentially due to advances in diagnosis, with registry data reporting an increase of between 200% and 300% in the last decade. It appears to be a more common disease in males, and the incidence of ATTRwt increases with age, with a mean age of diagnosis around 75 years, but cases have been reported in patients as young as 40, and many of the symptoms are known to precede diagnosis by years.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> With improved knowledge of the disease and the establishment of reference centres, this time interval has shortened, but was still 2.3 years for ATTRwt in the 2018–2021 period of the Transthyretin Amyloidosis Outcomes Survey (THAOS) registry.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Diagnosis</span><p id="par0030" class="elsevierStylePara elsevierViewall">Non-invasive testing should be initiated, but biopsy remains the gold standard for the diagnosis of the disease, especially in cases of high clinical suspicion with uncertain imaging results.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Diagnostic suspicion</span><p id="par0035" class="elsevierStylePara elsevierViewall">Amyloid deposition increases myocardial thickness and therefore this ventricular pseudohypertrophy is its guiding sign (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). HF is the primary syndrome associated with ATTRwt amyloidosis and in many cases is the trigger for its diagnosis. It usually results in higher natriuretic peptide and troponin levels than in other patients with preserved HF.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Conduction disturbances and supraventricular tachycardias are also common, and up to 16% of patients referred for transcatheter aortic valve implantation (TAVI) have the disease.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The need to reduce antihypertensive medication in a previously hypertensive patient or intolerance to the introduction of beta-blockers are also warning signs.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Peripheral neuropathy is much less common than in ATTRv but has been detected in up to 10% of cases. In addition, autonomic dysfunction, especially in the form of orthostatic hypotension and to a lesser extent with its other symptoms (diarrhoea, constipation, erectile dysfunction, etc.), has been reported in only 6–12% of patients with ATTRwt.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Orthopaedic manifestations are also relevant in the diagnosis and prognosis of ATTRwt. They are estimated to be present in up to 80% of ATTRwt patients and precede cardiac symptoms by 5–15 years, so they may help in early diagnosis, thus changing the natural course of the disease. Carpal tunnel syndrome is present in 20–60% of ATTRwt patients, and 30–50% of lumbar canal stenosis surgeries show transthyretin amyloid (TTR) in the specimens. Likewise, shoulder, knee or hip surgeries are common and more prevalent in patients with ATTRwt (46% in ATTRwt vs. 23% in ATTRv). In this sense, biopsies at the time of surgery would allow for an early diagnosis of the disease.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The most accessible non-invasive complementary examinations for suspected ATTRwt are electrocardiography and echocardiography.</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Electrocardiographic findings</span><p id="par0055" class="elsevierStylePara elsevierViewall">Myocardial infiltration by amyloid fibrils results in pseudohypertrophy with electrocardiogram discrepancy, showing low QRS voltages despite elevated myocardial thickness (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Therefore, the assessment of the ratio of QRS voltage to myocardial thickness is one of the first warning signs that should raise the suspicion of infiltrative cardiomyopathy. However, it is noteworthy that patients with ATTR cardiac disease (ATTR-CA) do not show as pronounced a reduction in voltage as patients with AL amyloidosis. Another typical ECG pattern is pseudoinfarction, which shows pathological Q waves in precordial leads, but is found in only 30–50% of ATTRwt.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In addition, up to 55% of patients with ATTRwt have atrial fibrillation (AF), and in 40% of cases, conduction disturbances are observed.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Echocardiographic findings</span><p id="par0060" class="elsevierStylePara elsevierViewall">Hypertrophy is usually concentric and biventricular, although in up to 20% of cases it may be asymmetric, and a granular/sparkling appearance of the myocardium is a common but non-specific sign.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Ejection fraction is preserved until late stages and does not adequately reflect systolic function in ATTR-CA.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Deterioration of longitudinal contractility usually precedes deterioration of radial function. Therefore, longitudinal strain measured by echocardiography with speckle tracking allows a more accurate estimation of longitudinal function and allows differentiation of amyloid cardiomyopathy from other pathologies with hypertrophy. Regional strain analysis of the left ventricle shows that the basal segments are more affected than the apical segments. This characteristic bull's eye pattern has a sensitivity of 92% and a specificity of 82% in discriminating amyloid cardiomyopathy, and deterioration of the overall longitudinal strain is associated with worse prognosis.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The coexistence of ventricular hypertrophy with atrial dilatation, significant diastolic dysfunction, atrial septal thickening, aortic stenosis (AS) or pericardial effusion should precipitate a high degree of suspicion.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Cardiac magnetic resonance imaging</span><p id="par0070" class="elsevierStylePara elsevierViewall">Cardiac magnetic resonance (CMR) imaging has revolutionised the non-invasive diagnosis of cardiomyopathies and, in addition to being more accurate than echocardiography in terms of cardiac function and structure, provides unique tissue characterisation through the administration of gadolinium. Gadolinium cannot pass through the myocardial cell and accumulates in the cellular space that is expanded by the amyloid deposition. Visualisation of this gadolinium deposition is performed using the late enhancement technique and T1-weighted contrast imaging to estimate the extracellular volume.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In a normal heart, the myocytes are close together and the extracellular volume is around 22–28%. As amyloid accumulates, this extracellular volume increases and late subendocardial and later transmural gadolinium retention occurs. Interpretation of late gadolinium retention images is not easy in the context of diffuse myocardial amyloid deposition and requires either a skilled operator to null the myocardium or the use of PSIR (phase sensitive inversion recovery) sequences. However, its widespread use is limited due to its low availability.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Diagnostic algorithm</span><p id="par0080" class="elsevierStylePara elsevierViewall">Once a high degree of clinical suspicion is reached, the diagnostic algorithm proposed by the scientific societies is initiated by performing a pyrophosphate cardiac scan and assessing the presence of monoclonal component in 24 h blood and urine, as well as the analysis of free light chains<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Nuclear medicine: cardiac scintigraphy</span><p id="par0085" class="elsevierStylePara elsevierViewall">Technetium-labelled bisphosphonate scintigraphy has proven to be an effective tool for detecting cardiac TTR amyloid deposits and has established itself as a highly specific technique for the diagnosis of ATTR-CA.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This paradigm shift provides a safer and less invasive alternative for diagnostic confirmation and the initiation of early targeted treatment.</p><p id="par0090" class="elsevierStylePara elsevierViewall">The degree of myocardial uptake is graded using a semi-quantitative visual score known as the Perugini score (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). However, the technique is not free of false positives and false negatives, which is why it is often used in conjunction with single photon emission computed tomography (SPECT).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The specificity of the technique for ATTR-CA is 86%, with false positives at the expense of cardiac uptake in patients with AL amyloidosis, which is why a complete haematological study should be performed. The combination of a score of 2 or 3 on scintigraphy with absence of monoclonal component increases the specificity of the test, with a positive predictive value for ATTR-CA close to 100%.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Haematological study</span><p id="par0095" class="elsevierStylePara elsevierViewall">In all patients with suspected amyloid cardiomyopathy, a haematological study with serum free light chain (FLC) analysis as well as 24 h immunofixation in blood and urine should be performed in addition to cardiac scintigraphy. The combination of these studies has a sensitivity of 99% for the identification of clonal dyscrasia in AL amyloidosis. In patients with chronic kidney disease or monoclonal gammopathy of uncertain significance, it is possible to find low levels of monoclonal protein or an abnormal FLC index (also known as kappa/lambda ratio). The normal range of the FLC index is 0.26 to 1.65; however, patients with chronic kidney disease may have FLC indices between 0.37 and 3.1 without this being a pathological result.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Interpretation of results</span><p id="par0100" class="elsevierStylePara elsevierViewall">Based on the results of the bisphosphonate scintigraphy and the result of the haematological study, the diagnostic algorithm can continue (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>), which should be interpreted as follows<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0105" class="elsevierStylePara elsevierViewall">In <span class="elsevierStyleItalic">absence of uptake on scintigraphy and absence of clonal dyscrasia</span> the likelihood of amyloid cardiomyopathy should be considered very low. An endomyocardial biopsy should only be performed in those cases where there is a very high suspicion of disease based on other complementary examinations or family history, as it could be a case of ATTRv.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0110" class="elsevierStylePara elsevierViewall">Given <span class="elsevierStyleItalic">negative scintigraphy and presence of clonal dyscrasia</span> the suspicion of AL amyloidosis is high and the study should be completed with a cardiac or extracardiac biopsy to demonstrate amyloid deposition.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0115" class="elsevierStylePara elsevierViewall">In the <span class="elsevierStyleItalic">presence of mild uptake (Perugini 1) and in the absence of clonal dyscrasia,</span> the diagnosis of ATTR amyloidosis cannot be confirmed and should be completed by cardiac or extracardiac biopsy.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0120" class="elsevierStylePara elsevierViewall">In the presence of <span class="elsevierStyleItalic">clonal dyscrasia with any type of uptake on scintigraphy (Perugini 1-3)</span> the aetiological diagnosis cannot be established with certainty. It could be amyloid cardiomyopathy due to TTR, AL or the coexistence of both pathologies. Endomyocardial biopsy will reveal the amyloid subtype that causes the heart disease.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">•</span><p id="par0125" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">presence of moderate or severe uptake (Perugini 2 or 3) without clonal dyscrasia</span> confirms the diagnosis of ATTR amyloidosis without the need for biopsy. The study should be completed with genetic testing to rule out ATTRv and the diagnosis of ATTRwt can then be confirmed.</p></li></ul></p></span></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Treating the clinical effects of cardiomyopathy</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Heart failure</span><p id="par0130" class="elsevierStylePara elsevierViewall">The evidence for the treatment of HF in ATTR-CA is still limited and clinical trials are needed to better establish drugs with prognostic benefit. The most recent retrospective studies give evidence of a potential mortality benefit from the use of aldosterone inhibitors. However, no differences have been detected in relation to treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and tolerance problems due to significant hypotension have been reported.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The use of beta-blockers is controversial because of their poor tolerability in the context of cardiomyopathy with a restrictive profile. In an American cohort of 309 patients diagnosed with de novo amyloidosis, discontinuation of previously prescribed beta-blocker therapy correlated with increased survival at follow-up.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In contrast, a recent retrospective analysis of a European cohort of more than 2,000 patients found a reduced risk of mortality in the subgroup of patients with depressed left ventricular ejection fraction treated with low-dose beta-blockers.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Clinical trials of sodium-glucose cotransporter type 2 (iSGLT2) inhibitors to date have excluded patients diagnosed with amyloid cardiomyopathy. A small retrospective study of patients with stable heart disease on tafamidis treatment described good tolerance to the initiation of iSGLT2; however, no information is available on its efficacy in this setting.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Loop diuretics are one of the mainstays of treatment in ATTR-CA, but, as with beta-blockers, the restrictive nature of the heart disease makes their use difficult given the need to achieve a balance between adequate decongestion and maintenance of optimal preload. The use of intravenous diuretics in hypervolemic states has been demonstrated to be safe<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Aortic stenosis</span><p id="par0150" class="elsevierStylePara elsevierViewall">The association between the presence of AS and ATTR-CA is common, representing up to 15% of all AS patients. Up to 30% of cases have a low flow-low gradient pattern (defined by a valve area ≤ 1.0 cm<span class="elsevierStyleSup">2</span>, an average gradient < 40 mmHg and a systolic volume index < 35 ml/m<span class="elsevierStyleSup">2</span>), and of these, up to 50% have preserved systolic function, known as paradoxical low flow-low gradient pattern. In addition, patients with severe AS in the context of ATTR-CA often have calcium levels that are disproportionately low in relation to the severity of the valvular heart disease, making it even more difficult to correctly grade the severity.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Due to the average age of presentation, TAVI is more common in ATTRwt than surgical valve replacement. TAVI implantation in patients with ATTR-CA has been shown to improve their prognosis with the same complication rate as in unaffected patients. Therefore, the presence of ATTR-CA per se should not be a reason to refuse treatment in the absence of other significant comorbidities.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Tachyarrhythmias</span><p id="par0160" class="elsevierStylePara elsevierViewall">AF is common in patients with ATTRwt due to restrictive cardiomyopathy and amyloid deposition at the atrial level. Its treatment is hampered by the intolerance of both high and low frequencies, as well as the aforementioned intolerance to beta-blockers; however, in the context of AF with rapid ventricular response, its use at low doses can be considered.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">The thromboembolic risk of ATTR-CA is very high due to significant atrial mechanical dysfunction, and in the presence of AF or flutter, initiation of anticoagulation is indicated regardless of the CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>VASC result. Thus, if a rhythm control strategy is chosen, the presence of thrombus should be ruled out prior to cardioversion even in patients with chronic anticoagulation.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Also due to low atrial contractility, the rhythm control strategy may be futile in the later stages of the disease, as the contribution of atrial contraction to stroke volume may be minimal even in sinus rhythm. In cases of very severe atrial dilatation coexisting with other parameters of dysfunction, such as decreased atrial strain, initiation of anticoagulation may be considered even in the absence of supraventricular arrhythmias.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Amiodarone is the antiarrhythmic agent with the best safety profile in ATTR-CA, both for rhythm and rate control.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Ventricular arrhythmias are more common in AL amyloidosis than in ATTR. The presence of non-sustained ventricular tachycardias has been associated with a higher proportion of defibrillator shocks at follow-up. However, the historically poor prognosis of this disease has discouraged the study of indications for defibrillator implantation in primary prevention and clinical guidelines recommend individualised assessment of each case.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Bradyarrhythmias</span><p id="par0180" class="elsevierStylePara elsevierViewall">Amyloid deposition can progressively affect conduction tissue with potential risk of advanced atrioventricular block, and up to 10% of patients eventually require pacemaker implantation at follow-up.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Bradycardia is especially poorly tolerated in patients with ATTRwt due to the low stroke volume of the heart disease, which can lead to dependence on cardiac pacing at increasingly higher rates to maintain an adequate cardiac output. In such a case, right ventricular pacing may lead to a deterioration of the left ventricular ejection fraction (LVEF) and functional class, especially when the pacing rate is higher than 40%, and a biventricular pacing device should therefore be considered when a high pacing rate is anticipated.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">The clinician’s challenge is to predict which patients will require pacemaker implantation. Porcari et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> described an increased risk of pacemaker implantation in patients with first degree AVB, QRS greater than 120 ms and a history of AF, with a negative predictive value of 92% in the absence of all three factors.</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Disease-modifying treatments</span><p id="par0195" class="elsevierStylePara elsevierViewall">The treatment of ATTR focuses on different points of the amyloid fibre formation cascade: synthesis of TTR at the hepatic level (therapeutic strategies to suppress synthesis), degradation of the tetrameric structure of TTR into dimers and monomers (stabilising molecules), and drugs responsible for the removal and degradation of amyloid fibrils. Most treatments were initially developed in patients with ATTRv neuropathy, but many have been shown to be useful in ATTR-CA as well (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Stabilising drugs</span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Diflunisal</span><p id="par0200" class="elsevierStylePara elsevierViewall">Diflunisal is a non-steroidal anti-inflammatory drug with the ability to stabilise the TTR molecule by binding to the T<span class="elsevierStyleInf">4</span> domain of TTR, reducing its breakdown into monomers and, consequently, the formation of fibrils. In the absence of clinical trials or prospective studies, its usefulness in ATTR-CA has been studied only in retrospective cohorts in which increased survival and stability in echocardiographic parameters were observed. However, its use has been limited by the adverse effects associated with the use of a non-steroidal anti-inflammatory drug.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Tafamidis</span><p id="par0205" class="elsevierStylePara elsevierViewall">Tafamidis is a small molecule that acts as a TTR stabiliser with a mechanism of action similar to diflunisal without the disadvantages associated with the anti-inflammatory effect. The ATTR-ACT study demonstrated reduced progression of heart disease with reduced all-cause mortality and cardiovascular hospitalisations in patients with ATTR-CA (75% <span class="elsevierStyleItalic">wild-type</span>). Tafamidis also slows the decline in patients’ functional capacity and quality of life.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> The extension phase of the clinical trial established the 80 mg dose as the most effective dose for treating heart disease associated with ATTR amyloidosis, demonstrating a greater survival benefit compared to the 20 mg<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> dose. Following these results, the European Medicines Agency approved the use of tafamidis free acid 61 mg (equivalent to 80 mg tafamidis meglumine) in the context of ATTR-CA, the only disease-modifying drug currently marketed for use in ATTR-CA.</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Acoramidis</span><p id="par0210" class="elsevierStylePara elsevierViewall">ATTRv patients carrying the T139M mutation are known to have increased protein stability with less dissociation of the tetrameric structure and therefore do not develop significant disease despite carrying a pathogenic variant in TTR. The AG10 molecule mimics the structure generated by the T119M mutation and consequently decreases fibril formation. The recently published clinical trial results show a decrease in all-cause mortality, heart failure admissions, as well as improved 6 minute walk test (6MWT) and quality of life questionnaire scores, compared to placebo.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Gene-silencing drugs</span><p id="par0215" class="elsevierStylePara elsevierViewall">Gene silencing drugs block messenger RNA transcription of the TTR gene by different mechanisms, resulting in a drastic reduction of hepatic TTR production.</p><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Patisiran</span><p id="par0220" class="elsevierStylePara elsevierViewall">Patisiran is a drug only approved for the treatment of polyneuropathy in ATTRv. However, results are available from the heart disease cohort of the APOLLO trial,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> developed in patients with ATTRv and neuropathy, which showed a decrease in myocardial thickness and levels of the N-terminal portion of brain natriuretic peptide (NT-proBNP), as well as from the APOLLO-B trial, which was developed in ATTR-CA with 89% of ATTRwt, in which an improvement in terms of functional capacity and quality of life was observed compared to placebo.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Inotersen</span><p id="par0225" class="elsevierStylePara elsevierViewall">The other drug currently approved for the treatment of neuropathy in ATTRv is inotersen, for which no robust results are currently available in ATTR-CA. A single-centre observational study of a small number of patients with heart disease showed improvement in functional capacity, in the absence of controlled clinical trials.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> The potential association of this drug with glomerulonephritis and severe thrombocytopenia has led to the development of novel second-generation molecules, such as eplontersen, which are designed to reduce the rate of adverse events and are currently in Phase III clinical trials for the treatment of ATTR-CA.</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Vutrisiran</span><p id="par0230" class="elsevierStylePara elsevierViewall">Vutrisiran is the third gene silencing drug for which preliminary evidence is also available in ATTR-CA. Exploratory analyses of the HELIOS-A trial in patients with ATTRv and polyneuropathy showed a trend towards improvement in both NT-proBNP levels and echocardiographic parameters.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> The HELIOS-B trial, currently under development, aims to investigate the efficacy of the drug in patients with both inherited and wild-type ATTR-CA <span class="elsevierStyleItalic">wild-type</span> (NCT04153149).</p></span></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Gene therapy</span><p id="par0235" class="elsevierStylePara elsevierViewall">Results are available from phase 1 trials with the drug NTLA-2001, a gene-editing molecule based on clustered regularly interspaced short palindromic repeats (CRISPR) that inactivates the TTR gene and consequently decreases its production by more than 90%.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Safety having been demonstrated, the results of the phase 3 trial (NCT04601051) are not yet available.</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Immunotherapy</span><p id="par0240" class="elsevierStylePara elsevierViewall">Encouraging results have recently been obtained on the possibility of removing TTR amyloid deposition from the heart using recombinant antibodies. Specifically, a recent phase 1 trial of recombinant NI006 antibody showed a decrease in tracer uptake on scintigraphy, as well as a trend towards reduced levels of NT-proBNP and troponins as surrogate markers of heart disease regression.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Monitoring and prognosis</span><p id="par0245" class="elsevierStylePara elsevierViewall">Monitoring of treatment and disease progression is based on three pillars: clinical and functional capacity variables; laboratory biomarkers; and imaging tests together with electrocardiograms. As clinicians, ensure that an assessment of these three parameters is carried out at a recommended frequency of 6 to 12 months<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).</p><p id="par0250" class="elsevierStylePara elsevierViewall">Both deterioration in functional class and the presence of HF admissions or decompensation are warnings of disease progression. However, regular monitoring using quality of life scales and objective functional assessment tests such as the 6MWT is also recommended.</p><p id="par0255" class="elsevierStylePara elsevierViewall">Circulating biomarkers are tools for diagnosis and risk stratification of patients. Multiple studies have shown an inverse relationship between increased NT-proBNP and troponins and reduced glomerular filtration rate and survival. Specifically, a 30% increase in NT-proBNP with a cut-off point of 300 pg/ml and a 30% increase in high-sensitivity troponins are suggestive of disease progression.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Imaging changes provide guidance on the stage of the disease, with changes in global longitudinal strain or filling pressures in early stages, and systolic dysfunction and atrial dilatation in later stages.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Recent studies suggest that CMR may allow monitoring of heart disease regression after the initiation of disease-modifying treatments.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> The mechanism by which cardiac uptake is observed on bisphosphonate scintigraphy is unknown and its validity in monitoring response to treatment has not yet been well studied.</p><p id="par0265" class="elsevierStylePara elsevierViewall">Organising the care of patients with ATTR-CA through a multidisciplinary and protocol-based approach, covering the entire care process from diagnostic suspicion to treatment monitoring, will improve early diagnosis and access to treatment, leading to an improvement in quality of life and survival.</p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conclusion</span><p id="par0270" class="elsevierStylePara elsevierViewall">ATTRwt is a common disease with high morbidity and mortality. Today, its diagnosis is widely available and its complications are well known. Advances in treatment are making it possible to improve both life expectancy and quality of life for patients. For this purpose, early diagnosis of the disease and wide accessibility of new treatments must be ensured.</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Ethical considerations</span><p id="par0275" class="elsevierStylePara elsevierViewall">No analysis of patient data or interventions was involved in the preparation of this article. Images of complementary examinations shown are anonymised and patients have signed an informed consent for the use of these images.</p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Funding</span><p id="par0280" class="elsevierStylePara elsevierViewall">None.</p></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conflict of interest</span><p id="par0285" class="elsevierStylePara elsevierViewall">L. Herrador has no conflict of interest; S. Yun has received financial compensation for educational activities from Pfizer in the last 5 years; J. González-Costello has received financial compensation for educational activities or scientific consulting from Pfizer, Alnylam, AstraZeneca, Novartis, and Boehringer-Ingelheim in the last 5 years.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Epidemiology" ] 2 => array:3 [ "identificador" => "sec0015" "titulo" => "Diagnosis" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0020" "titulo" => "Diagnostic suspicion" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Electrocardiographic findings" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Echocardiographic findings" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Cardiac magnetic resonance imaging" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Diagnostic algorithm" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Nuclear medicine: cardiac scintigraphy" ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "Haematological study" ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Interpretation of results" ] ] ] ] ] 3 => array:3 [ "identificador" => "sec0060" "titulo" => "Treating the clinical effects of cardiomyopathy" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Heart failure" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Aortic stenosis" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "Tachyarrhythmias" ] 3 => array:2 [ "identificador" => "sec0080" "titulo" => "Bradyarrhythmias" ] ] ] 4 => array:3 [ "identificador" => "sec0085" "titulo" => "Disease-modifying treatments" "secciones" => array:4 [ 0 => array:3 [ "identificador" => "sec0090" "titulo" => "Stabilising drugs" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0095" "titulo" => "Diflunisal" ] 1 => array:2 [ "identificador" => "sec0100" "titulo" => "Tafamidis" ] 2 => array:2 [ "identificador" => "sec0105" "titulo" => "Acoramidis" ] ] ] 1 => array:3 [ "identificador" => "sec0110" "titulo" => "Gene-silencing drugs" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0115" "titulo" => "Patisiran" ] 1 => array:2 [ "identificador" => "sec0120" "titulo" => "Inotersen" ] 2 => array:2 [ "identificador" => "sec0125" "titulo" => "Vutrisiran" ] ] ] 2 => array:2 [ "identificador" => "sec0130" "titulo" => "Gene therapy" ] 3 => array:2 [ "identificador" => "sec0135" "titulo" => "Immunotherapy" ] ] ] 5 => array:2 [ "identificador" => "sec0140" "titulo" => "Monitoring and prognosis" ] 6 => array:2 [ "identificador" => "sec0145" "titulo" => "Conclusion" ] 7 => array:2 [ "identificador" => "sec0150" "titulo" => "Ethical considerations" ] 8 => array:2 [ "identificador" => "sec0155" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0160" "titulo" => "Conflict of interest" ] 10 => array:2 [ "identificador" => "xack768280" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-09-16" "fechaAceptado" => "2024-03-07" "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2044 "Ancho" => 2167 "Tamanyo" => 259423 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Warning signs for suspected diagnosis of non-hereditary or <span class="elsevierStyleItalic">wild-type</span> (ATTRwt) ATTR amyloidosis.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">ECG: electrocardiogram; TTE: transthoracic echocardiogram; HT: hypertension; CMR: cardiac magnetic resonance imaging; ECV: extracellular volume.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2160 "Ancho" => 3333 "Tamanyo" => 694740 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Complementary examinations of a patient with ATTRwt. 1) Typical electrocardiogram with disproportionately decreased voltages for the hypertrophy seen on imaging, pseudoinfarction pattern with Q wave in V1–V2 and atrial fibrillation. 2) Transthoracic echocardiogram with hypertrophy of the wall of both ventricles, granular appearance of the interventricular septum (a phenomenon known as <span class="elsevierStyleItalic">sparkling</span>) and atrial dilatation. 3)  Regional Left Ventricular Strain with bull's eye pattern (preservation of apical segment contractility and increased basal segment involvement). 4) Pyrophosphate scintigraphy showing a Perugini score of  3. 5) MRI with late gadolinium enhancement sequence in the long axis showing extensive fibrosis of the left atrium and subendocardial fibrosis at septal level. 6) Cardiac magnetic resonance cine imaging showing hypertrophy of both ventricles and atrial dilatation.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2069 "Ancho" => 3333 "Tamanyo" => 629296 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Semi-quantitative visual score of pyrophosphate scintigraphy (Perugini score) and diagnostic algorithm for amyloid cardiomyopathy based on the score.</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">AL: light chain amyloidosis; ATTR: transthyretin amyloidosis; ATTRv: hereditary transthyretin amyloidosis; EMB: endomyocardial biopsy.</p>" ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1570 "Ancho" => 2580 "Tamanyo" => 479439 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Key points on new evidence in the management of complications of cardiac transthyretin amyloidosis (ATTR-CA).</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">AS: aortic stenosis; AF: atrial fibrillation; SLGT2i: sodium-glucose cotransporter-2 inhibitors; MRAs: mineralocorticoid receptor antagonists (aldosterone inhibitors); TAVI: transcatheter aortic valve implantation.</p>" ] ] 4 => array:8 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 2620 "Ancho" => 1833 "Tamanyo" => 309794 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">ATTR wild-type disease modifying treatments and signs of ATTR progression taking into account clinical variables, imaging, electrocardiography and biomarkers.</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">AVB: atrioventricular block; BBB: bundle branch block; LVEF: left ventricular ejection fraction; HF: heart failure; NYHA: <span class="elsevierStyleItalic">New York Heart Association</span>; TnI: high-sensitivity troponin; 6-MWT: 6 minute walk test.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Garcia-Pavia" 1 => "C. Rapezzi" 2 => "Y. Adler" 3 => "M. Arad" 4 => "C. Basso" 5 => "A. Brucato" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehab072" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2021" "volumen" => "42" "paginaInicial" => "1554" "paginaFinal" => "1568" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33825853" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estimating the prevalence of cardiac amyloidosis in old patients with heart failure—barriers and opportunities for improvement: the PREVAMIC study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Ruiz-Hueso" 1 => "P. Salamanca-Bautista" 2 => "M.A. Quesada-Simón" 3 => "S. Yun" 4 => "A. Conde-Martel" 5 => "J.L. Morales-Rull" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/jcm12062273" "Revista" => array:6 [ "tituloSerie" => "J Clin Med" "fecha" => "2023" "volumen" => "12" "paginaInicial" => "2273" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36983274" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0165587615000324" "estado" => "S300" "issn" => "01655876" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Patients with transthyretin amyloidosis enrolled in THAOS between 2018 and 2021 continue to experience substantial diagnostic delay" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "THAOS investigators" "etal" => true "autores" => array:5 [ 0 => "T. Coelho" 1 => "A. Dispenzieri" 2 => "M. Grogan" 3 => "I. Conceição" 4 => "M Waddington-Cruz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/13506129.2023.2229484" "Revista" => array:7 [ "tituloSerie" => "Amyloid" "fecha" => "2023" "volumen" => "30" "paginaInicial" => "445" "paginaFinal" => "448" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37459334" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0165587613006125" "estado" => "S300" "issn" => "01655876" ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nonbiopsy diagnosis of cardiac transthyretin amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.D. Gillmore" 1 => "M.S. Maurer" 2 => "R.H. Falk" 3 => "G. Merlini" 4 => "T. Damy" 5 => "A. Dispenzieri" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Circulation" "fecha" => "2016" "volumen" => "133" "paginaInicial" => "2404" "paginaFinal" => "2412" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence and outcome of dual aortic stenosis and cardiac amyloid pathology in patients referred for transcatheter aortic valve implantation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.R. Scully" 1 => "K.P. Patel" 2 => "T.A. Treibel" 3 => "G.D. Thornton" 4 => "R.K. Hughes" 5 => "S. Chadalavada" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehaa170" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2020" "volumen" => "41" "paginaInicial" => "2759" "paginaFinal" => "2767" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32267922" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "F.L. Ruberg" 1 => "M. Grogan" 2 => "M. Hanna" 3 => "J.W. Kelly" 4 => "MS Maurer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2019.04.003" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2019" "volumen" => "73" "paginaInicial" => "2872" "paginaFinal" => "2891" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31171094" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical characteristics of wild-type transthyretin cardiac amyloidosis: disproving myths" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. González-López" 1 => "C. Gagliardi" 2 => "F. Dominguez" 3 => "C.C. Quarta" 4 => "F.J. De Haro-Del Moral" 5 => "A. Milandri" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Eur Heart J" "fecha" => "2017" "volumen" => "38" "paginaInicial" => "1895" "paginaFinal" => "1904" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hand surgeons and amyloidosis specialists warning: transthyretin-associated amyloidosis with bifid median nerve as a cause of bilateral carpal tunnel syndrome. A case report and literature review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Triguero" 1 => "J. González-Costello" 2 => "S. López-Marne" 3 => "A. Llop" 4 => "M. Pané" 5 => "S. Yun" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00590-021-03004-1" "Revista" => array:6 [ "tituloSerie" => "Eur J Orthop Surg Traumatol" "fecha" => "2022" "volumen" => "32" "paginaInicial" => "575" "paginaFinal" => "581" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34050818" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac structural and functional consequences of amyloid deposition by cardiac magnetic resonance and echocardiography and their prognostic roles" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.S. Knight" 1 => "G. Zumbo" 2 => "W. Barcella" 3 => "J.A. Steeden" 4 => "V. Muthurangu" 5 => "A. Martinez-Naharro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcmg.2018.02.016" "Revista" => array:6 [ "tituloSerie" => "JACC Cardiovasc Imaging" "fecha" => "2019" "volumen" => "12" "paginaInicial" => "823" "paginaFinal" => "833" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29680336" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lack of association between neurohormonal blockade and survival in transthyretin cardiac amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.K. Cheng" 1 => "A. Vasbinder" 2 => "W.C. Levy" 3 => "P. Goyal" 4 => "J.M. Griffin" 5 => "D.J. Leedy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/JAHA.121.022859" "Revista" => array:3 [ "tituloSerie" => "J Am Heart Assoc" "fecha" => "2021" "volumen" => "10" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Conventional heart failure therapy in cardiac ATTR amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Ioannou" 1 => "P. Massa" 2 => "R.K. Patel" 3 => "Y. Razvi" 4 => "A. Porcari" 5 => "M.U. Rauf" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehad347" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2023" "volumen" => "44" "paginaInicial" => "2893" "paginaFinal" => "2907" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37216684" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "SGLT2 inhibitor therapy for transthyretin amyloid cardiomyopathy: early tolerance and clinical response to dapagliflozin" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Dobner" 1 => "B. Bernhard" 2 => "B. Asatryan" 3 => "S. Windecker" 4 => "S. Stortecky" 5 => "T. Pilgrim" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "ESC Hear Fail" "fecha" => "2023" "volumen" => "10" "paginaInicial" => "397" "paginaFinal" => "404" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ATTR amyloidosis: current and emerging management strategies: JACC: CardioOncology State-of-the-Art Review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.M. Griffin" 1 => "J.L. Rosenthal" 2 => "J.L. Grodin" 3 => "M.S. Maurer" 4 => "M. Grogan" 5 => "RK Cheng" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaccao.2021.06.006" "Revista" => array:6 [ "tituloSerie" => "JACC CardioOncology" "fecha" => "2021" "volumen" => "3" "paginaInicial" => "488" "paginaFinal" => "505" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34729521" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac amyloidosis: evolving diagnosis and management: a scientific statement from the American Heart Association" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.M. Kittleson" 1 => "M.S. Maurer" 2 => "AV Ambardekar" 3 => "R.P. Bullock-Palmer" 4 => "P.P. Chang" 5 => "H.J. Eisen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIR.0000000000000792" "Revista" => array:5 [ "tituloSerie" => "Circulation" "fecha" => "2020" "volumen" => "142" "paginaInicial" => "e7" "paginaFinal" => "e22" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Direct current cardioversion of atrial arrhythmias in adults with cardiac amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.A. El-Am" 1 => "A. Dispenzieri" 2 => "R.M. Melduni" 3 => "N.M. Ammash" 4 => "R.D. White" 5 => "D.O. Hodge" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2018.10.079" "Revista" => array:7 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2019" "volumen" => "73" "paginaInicial" => "589" "paginaFinal" => "597" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30732713" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0012369220318535" "estado" => "S300" "issn" => "00123692" ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Implantable cardioverter-defibrillator placement in patients with cardiac amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.C. Varr" 1 => "S. Zarafshar" 2 => "T. Coakley" 3 => "M. Liedtke" 4 => "R.A. Lafayette" 5 => "S. Arai" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Hear Rhythm" "fecha" => "2014" "volumen" => "11" "paginaInicial" => "158" "paginaFinal" => "162" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac devices in patients with transthyretin amyloidosis: impact on functional class, left ventricular function, mitral regurgitation, and mortality" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Donnellan" 1 => "O.M. Wazni" 2 => "W.I. Saliba" 3 => "B. Baranowski" 4 => "M. Hanna" 5 => "M. Martyn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jce.14180" "Revista" => array:6 [ "tituloSerie" => "J Cardiovasc Electrophysiol" "fecha" => "2019" "volumen" => "30" "paginaInicial" => "2427" "paginaFinal" => "2432" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31515942" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence and risk factors for pacemaker implantation in light-chain and transthyretin cardiac amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Porcari" 1 => "M. Rossi" 2 => "F. Cappelli" 3 => "M. Canepa" 4 => "B. Musumeci" 5 => "A. Cipriani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ejhf.2533" "Revista" => array:6 [ "tituloSerie" => "Eur J Heart Fail" "fecha" => "2022" "volumen" => "24" "paginaInicial" => "1227" "paginaFinal" => "1236" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35509181" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Stabilization of Cardiac Function With Diflunisal in Transthyretin (ATTR) cardiac amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Lohrmann" 1 => "A. Pipilas" 2 => "R. Mussinelli" 3 => "D.M. Gopal" 4 => "J.L. Berk" 5 => "L.H. Connors" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cardfail.2019.11.024" "Revista" => array:6 [ "tituloSerie" => "J Card Fail" "fecha" => "2020" "volumen" => "26" "paginaInicial" => "753" "paginaFinal" => "759" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31805416" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.S. Maurer" 1 => "J.H. Schwartz" 2 => "B. Gundapaneni" 3 => "P.M. Elliott" 4 => "G. Merlini" 5 => "M. Waddington-Cruz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1805689" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2018" "volumen" => "379" "paginaInicial" => "1007" "paginaFinal" => "1016" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30145929" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0012369217330738" "estado" => "S300" "issn" => "00123692" ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Damy" 1 => "P. Garcia-Pavia" 2 => "M. Hanna" 3 => "D.P. Judge" 4 => "G. Merlini" 5 => "B. Gundapaneni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ejhf.2027" "Revista" => array:6 [ "tituloSerie" => "Eur J Heart Fail" "fecha" => "2021" "volumen" => "23" "paginaInicial" => "277" "paginaFinal" => "285" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33070419" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.D. Gillmore" 1 => "D.P. Judge" 2 => "F. Cappelli" 3 => "M. Fontana" 4 => "P. Garcia-Pavia" 5 => "S. Gibbs" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa2305434" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2024" "volumen" => "390" "paginaInicial" => "132" "paginaFinal" => "142" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/38197816" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Letter by González-Costello et al. Regarding Article, “effects of Patisiran, an RNA interference therapeutic, on cardiac parameters in patients with hereditary transthyretin-mediated amyloidosis: analysis of the APOLLO study”" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. González-Costello" 1 => "C. Casasnovas" 2 => "C. Díez-López" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.119.039645" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2019" "volumen" => "140" "paginaInicial" => "e90" "paginaFinal" => "e91" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31283374" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Patisiran treatment in patients with transthyretin cardiac amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.S. Maurer" 1 => "P. Kale" 2 => "M. Fontana" 3 => "J.L. Berk" 4 => "M. Grogan" 5 => "F. Gustafsson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa2300757" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2023" "volumen" => "389" "paginaInicial" => "1553" "paginaFinal" => "1565" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37888916" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0104001413001978" "estado" => "S300" "issn" => "01040014" ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inotersen therapy of transthyretin amyloid cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "N.R. Dasgupta" 1 => "S.M. Rissing" 2 => "J. Smith" 3 => "J. Jung" 4 => "M.D. Benson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/13506129.2019.1685487" "Revista" => array:6 [ "tituloSerie" => "Amyloid" "fecha" => "2020" "volumen" => "27" "paginaInicial" => "52" "paginaFinal" => "58" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31713445" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Helios-a: Results from the phase 3 study of vutrisiran in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Gonzalez-Duarte" 1 => "D. Adams" 2 => "I. Tournev" 3 => "M. Taylor" 4 => "T. Coelho" 5 => "V. Plante-Bordeneuve" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2022" "volumen" => "79" "numero" => "9" "paginaInicial" => "302" ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CRISPR-cas9 in vivo gene editing for transthyretin amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.D. Gillmore" 1 => "E. Gane" 2 => "J. Taubel" 3 => "J. Kao" 4 => "M. Fontana" 5 => "M.L. Maitland" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa2107454" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2021" "volumen" => "385" "paginaInicial" => "493" "paginaFinal" => "502" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34215024" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phase 1 trial of antibody ni006 for depletion of cardiac transthyretin amyloid" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P Garcia-Pavia" 1 => "F aus dem Siepen" 2 => "E Donal" 3 => "O Lairez" 4 => "P van der Meer" 5 => "AV Kristen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2023" "volumen" => "389" "paginaInicial" => "239" "paginaFinal" => "250" "itemHostRev" => array:3 [ "pii" => "S1526590017305199" "estado" => "S300" "issn" => "15265900" ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expert consensus on the monitoring of transthyretin amyloid cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Garcia-Pavia" 1 => "F. Bengel" 2 => "D. Brito" 3 => "T. Damy" 4 => "F. Duca" 5 => "S. Dorbala" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ejhf.2198" "Revista" => array:6 [ "tituloSerie" => "Eur J Heart Fail" "fecha" => "2021" "volumen" => "23" "paginaInicial" => "895" "paginaFinal" => "905" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33915002" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reduction in CMR derived extracellular volume with patisiran indicates cardiac amyloid regression" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Fontana" 1 => "A. Martinez-Naharro" 2 => "L. Chacko" 3 => "D. Rowczenio" 4 => "J.A. Gilbertson" 5 => "C.J. Whelan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcmg.2020.07.043" "Revista" => array:6 [ "tituloSerie" => "JACC Cardiovasc Imaging" "fecha" => "2021" "volumen" => "14" "paginaInicial" => "189" "paginaFinal" => "199" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33129740" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack768280" "titulo" => "Acknowledgements" "texto" => "<p id="par0290" class="elsevierStylePara elsevierViewall">We are grateful to the CERCA/Generalitat de Catalunya programme for the institutional support.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000016300000003/v1_202408230644/S2387020624003152/v1_202408230644/en/main.assets" "Apartado" => array:4 [ "identificador" => "97285" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Special Section: Transthyretin amyloidosis" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000016300000003/v1_202408230644/S2387020624003152/v1_202408230644/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624003152?idApp=UINPBA00004N" ]