ABSTRACT
RESUMEN: La cardiomiopatía amiloide por transtiretina (CATTR) es una enfermedad caracterizada por depósito extracelular de fibrillas amiloides en el miocardio, a partir de transtiretina mal plegada, generando una miocardiopatía restrictiva. Esta proteína mal plegada puede tener origen hereditario o adquirido, siendo más frecuente en adultos mayores. La CA-TTR ha surgido como una causa subdiagnosticada de insuficiencia cardíaca con fracción de eyección preservada (IC FEp). El pilar fundamental para su diagnóstico es la alta sospecha clínica, basada en diversas banderas de alerta ya que la sintomatología que provoca suele ser inespecífica. Como veremos en esta revisión, el diagnóstico puede sustentarse con la cintigrafía ósea, reservando para situaciones particulares la toma de biopsia. Con el advenimiento de nuevas terapias que impactan en la sobrevida de esta enfermedad, el tiempo para realizar el diagnóstico certero y la diferenciación de otras causas de amiloidosis cardíaca como la de cadenas livianas, se ha tornado crucial.
ABSTRACT: Transthyretin amyloid cardiomyopathy (AT-TR-CM) is a disease characterized by extracellular deposition of amyloid fibrils in the myocardium, from misfolded transthyretin, generating a restrictive cardiomyopathy. This misfolded protein may be inherited or acquired, and is more prevalent in elderly patients. ATTR-CM has emerged as an underdiagnosed cause of heart failure with preserved ejection fraction (HF-PEF). The fundamental pillarfor its diagnosis is high clinical suspicion since the symptoms are usually nonspecific. The diagnosis can be made from bone scintigraphy, reserving myocardial biopsy for particular situations. With the advent of new therapies that affect the survival of these patients, a timely diagnosis has become crucial.
Subject(s)
Humans , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/therapy , Cardiomyopathies/diagnosis , Cardiomyopathies/therapy , Prealbumin , Diagnosis, Differential , Heart Failure/diagnosis , Heart Failure/etiology , Heart Failure/therapyABSTRACT
ABSTRACT Transthyretin familial amyloid polyneuropathy is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy, which if untreated, leads to death in approximately 10 years. In Brazil, liver transplant and tafamidis are the only disease-modifying treatments available. This review consists of a consensus for the diagnosis, management and treatment for transthyretin familial amyloid polyneuropathy from the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology. The first and last authors produced a draft summarizing the main views on the subject and emailed the text to 10 other specialists. Relevant literature on this subject was reviewed by each participant and used for the individual review of the whole text. Each participant was expected to review the text and send a feedback review by e-mail. Thereafter, the 12 panelists got together at the city of Fortaleza, discussed the controversial points, and reached a consensus for the final text.
RESUMO Polineuropatia amiloidótica familiar é uma polineuropatia sensitivo-motora e autonômica de herança autossômica dominante, que caso não seja tratada leva a morte em aproximadamente 10 anos. O transplante de fígado e o tafamidis são os únicos tratamentos disponíveis no Brasil. Essa revisão consiste em um consenso do Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia. O primeiro e último autores produziram um texto resumindo os principais aspectos sobre o tema e enviaram para os outros 10 especialistas por email. A literatura relevante sobre o assunto foi revisada por cada participante e utilizada para revisão individual do texto. Foi esperado que cada participante revisasse o texto e enviasse suas sugestões por e-mail. Finalmente, os 12 panelistas se encontraram na cidade de Fortaleza para discutir os pontos controversos e chegar a um consenso sobre texto final.
Subject(s)
Humans , Animals , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/therapy , Oligonucleotides/therapeutic use , Benzoxazoles/therapeutic use , Brazil , Randomized Controlled Trials as Topic , Amyloid Neuropathies, Familial/pathology , Amyloid Neuropathies, Familial/drug therapy , RNA, Small Interfering/therapeutic use , Diagnosis, Differential , Cardiomyopathies/complicationsABSTRACT
La polineuropatía amiloidótica familiar asociada a transtiretina (PAF-TTR) es una enfermedad hereditaria con distribución geográfica variable. El objetivo de este trabajo fue presentar nuestra experiencia con pacientes con PAF-TTR. Se evaluaron retrospectivamente 9 casos pertenecientes a diferentes familias. Los criterios diagnósticos utilizados se basaron en la combinación de un cuadro clínico compatible, hallazgos histopatológicos y confirmación genética. Cinco casos mostraron la presentación clásica y 4 la variante de inicio tardío. La mutación p.Val30Met en el gen TTR fue hallada en 6 casos y p.Ala36Pro, p.Thr60Ala y p.Tyr114Cys en los 3 los restantes, respectivamente. La edad media de inicio fue 35 años (rango 26-60). El tiempo medio al diagnóstico fue de 4.2 ± 1.5 años. Siete pacientes recibieron diagnóstico erróneo inicial, 3 de la variante clásica y 4 de la tardía. Nuestra serie de pacientes mostró marcada heterogeneidad en la presentación clínica del grupo de PAF-TTR de inicio tardío, en una región no endémica de Sudamérica.
Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is a hereditary disease with variable geographical distribution. The aim of this study was to present our experience with TTR-FAP patients. We retrospectively analyzed nine cases belonging to different families. Diagnostic criteria were based on the combination of compatible clinical picture, histopathological findings and genetic confirmation. Five cases showed the classic presentation and other 4 the late onset variant. The p.Val30Met mutation in the TTR gene was found in 6 cases and p.Ala36Pro, p.Thr60Ala and p.Tyr114Cys in the remaining 3, respectively. The median age of symptom onset was 35 years (26-60 range). Mean time to diagnosis was 4.2 ± 1.5 years. Our patient series showed the heterogeneity in clinical presentation of TTR-FAP in a non-endemic region of South America.