Challenges in the approach to a patient with aortic stenosis and cardiac amyloidosis with ATTR mutation associated with negative scintigraphy - A case report.

Introduction: Cardiac amyloidosis (CA) poses significant diagnostic and therapeutic challenges. In this case report, we detail a patient with CA due to a rare transthyretin (CA-TTR) mutation, manifesting with negative myocardial scintigraphy and requiring genetic testing for diagnosis. The patient also had severe aortic stenosis (AS), necessitating discussion with a heart team to determine the optimal treatment strategy. Case report: A 70-year-old male with a family history of sudden death was previously diagnosed with third-degree atrioventricular block and treated with a pacemaker. He presented with worsening exertional dyspnoea, and examination revealed a third heart sound, a systolic murmur indicative of AS and bilateral muscular atrophy in the thenar region. Transthoracic echocardiography indicated severe AS and moderate left ventricular dysfunction, with images suggesting infiltrative disease. Pyrophosphate scintigraphy revealed no abnormal cardiac tracer uptake. Cardiac magnetic resonance imaging (MRI) revealed extensive, heterogeneous, subendocardial late gadolinium enhancement in both the atria and ventricles, which was consistent with CA. Genetic testing identified the Phe84Leu mutation in the TTR gene. Following heart team discussions, the patient underwent successful transcatheter aortic valve implantation (TAVI) and remained asymptomatic in follow-up, being monitored at an outpatient clinic specializing in CA and using tafamidis. Discussion: CA-TTR can be an autosomal dominant disease with variable penetrance involving abnormal amyloid protein deposition in tissues and can often be diagnosed noninvasively via myocardial scintigraphy. However, some TTR mutations do not affect scintigraphy results, necessitating genetic testing when clinical suspicion is high, potentially avoiding endomyocardial biopsy. Moreover, AS occurs in up to 16 % of TTR amyloidosis patients, with the conditions mutually exacerbating each other. Recent consensus suggests that TAVI reduces mortality in patients with severe AS and amyloidosis. Conclusions: Various diagnostic algorithms emphasize the use of myocardial scintigraphy for suspected CA-TTR. Genetic testing is crucial when scintigraphy results are negative, but clinical suspicion remains high, potentially circumventing invasive procedures. Compared with medical management alone, TAVI has been shown to improve quality of life and survival in patients with concurrent severe AS and CA.

Advances in the Diagnosis and Management of Cardiac Amyloidosis: A Literature Review.

Cardiac amyloidosis, increasingly recognized for its significant impact on global heart health and patient survival, demands a thorough review to understand its complexity and the urgency of improved management strategies. As a cause of cardiomyopathy and heart failure, particularly in patients with aortic stenosis and atrial fibrillation, this condition also relates to higher incidences of dementia in the affected populations. The objective of this review was to integrate and discuss the latest advancements in diagnostics and therapeutics for cardiac amyloidosis, emphasizing the implications for patient prognosis. We evaluated the latest literature from major medical databases such as PubMed and Scopus, focusing on research from 2020 to 2024, to gather comprehensive insights into the current landscape of this condition. Insights from our review highlight the complex pathophysiology of cardiac amyloidosis and the diagnostic challenges it presents. We detail the effectiveness of emerging treatments, notably gene silencing therapies like patisiran and vutrisiran, which offer transformative potential by targeting the production of amyloidogenic proteins. Additionally, the stabilization therapy acoramidis shows promise in modifying disease progression and improving clinical outcomes. This review underscores the critical need for updated clinical guidelines and further research to expand access to groundbreaking therapies and enhance disease management. Advocating for continued research and policy support, we emphasize the importance of advancing diagnostic precision and treatment effectiveness, which are vital for improving patient outcomes and addressing this debilitating disease globally.

Cardiac Amyloidosis in Venezuela: A Pending Issue.

Cardiac amyloidosis (CA) is an infiltrative disease characterized by the deposition of misfolded proteins in cardiac interstitial tissue. Interest towards studying this pathology has been growing in the last decade, as new epidemiological insights have revealed that it is not as uncommon as previously believed. Likewise, advances in non-invasive diagnostic approaches and the identification of molecules that modify its long-term progression, even in terms of mortality, have also bolstered interest in CA. Despite this global panorama, in Venezuela, limitations remain regarding the diagnosis of CA, partly associated with a lack of knowledge of the disease. Therefore, additional efforts are necessary for clinical cardiologists to hone their diagnostic skills regarding this disease, as opportune identification is an essential step for its effective management.

Clinical and genetic profiles of patients with hereditary and wild-type transthyretin amyloidosis: the Transthyretin Cardiac Amyloidosis Registry in the state of São Paulo, Brazil (REACT-SP).

BACKGROUND: Transthyretin amyloidosis (ATTR) is a multisystem disease caused by the deposition of fibrillar protein in organs and tissues. ATTR genotypes and phenotypes are highly heterogeneous. We present data on physical signs and symptoms, cardiac and neurological assessments and genetic profile of patients enrolled in the Transthyretin Cardiac Amyloidosis Registry of the State of São Paulo, Brazil. RESULTS: Six hundred-forty-four patients were enrolled, 505 with the variant form (ATTRv) and 139 with wild-type (ATTRwt). Eleven different mutations were detected, the most common being Val50Met (47.5%) and V142Ile (39.2%). Overall, more than half of the patients presented cardiac involvement, and the difference in this proportion between the ATTRv and ATTRwt groups was significant (43.9 vs. 89.9%; p < 0.001). The prevalence of the neurological phenotype also differed between ATTRv and ATTRwt (56.8 vs. 31.7%; p < 0.001). The mixed phenotype was found in 25.6% of the population, without a significant difference between ATTRv and ATTRwt groups. A group of patients remained asymptomatic (10.4%), with a lower proportion of asymptomatic ATTRwt patients. CONCLUSIONS: This study details the clinical and genetic spectrum of patients with ATTR in São Paulo, Brazil. This preliminary analysis highlights the considerable phenotypic heterogeneity of neurological and cardiac manifestations in patients with variant and wild-type ATTR.

Multinational experience with next-generation sequencing: opportunity to identify transthyretin cardiac amyloidosis and Fabry disease.

Background: Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. We tested the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates. Identification of transthyretin cardiac amyloidosis (ATTR-CA) and Fabry disease (FD) is essential because of the availability of disease-specific therapy. Early initiation of these treatments may lead to better clinical outcomes. Methods: In this international, multicenter, cross-sectional pilot study, peripheral dried blood spot samples from patients of cardiology clinics with an unexplained increased left ventricular wall thickness (LVWT) of ≥13 mm in one or more left ventricular myocardial segments (measured by imaging methods) were analyzed at a central laboratory. NGS included the detection of known splice regions and flanking regions of 17 genes using the Illumina NextSeq 500 and NovaSeq 6000 sequencing systems. Results: Samples for NGS screening were collected between May 2019 and October 2020 at cardiology clinics in Colombia, Brazil, Mexico, Turkey, Israel, and Saudi Arabia. Out of 535 samples, 128 (23.9%) samples tested positive for pathogenic/likely pathogenic genetic variants associated with HCM or HCM phenocopies with double pathogenic/likely pathogenic variants detected in four samples. Among the 132 (24.7%) detected variants, 115 (21.5%) variants were associated with HCM and 17 (3.2%) variants with HCM phenocopies. Variants in MYH7 (n=60, 11.2%) and MYBPC3 (n=41, 7.7%) were the most common HCM variants. The HCM phenocopy variants included variants in the TTR (n=7, 1.3%) and GLA (n=2, 0.4%) genes. The mean (standard deviation) ages of patients with HCM or HCM phenocopy variants, including TTR and GLA variants, were 42.8 (17.9), 54.6 (17.0), and 69.0 (1.4) years, respectively. Conclusions: The overall diagnostic yield of 24.7% indicates that the screening strategy effectively identified the most common forms of HCM and HCM phenocopies among geographically dispersed patients. The results underscore the importance of including ATTR-CA (TTR variants) and FD (GLA variants), which are treatable disorders, in the differential diagnosis of patients with increased LVWT of unknown etiology.

Fibrilación auricular en amiloidosis por transtirretina / Atrial fibrillation in transthyretin amyloidosis

Resumen La amiloidosis cardiaca es una enfermedad que se caracteriza por el depósito de material amiloide en la matriz extracelular del miocardio. Las arritmias son parte del amplio espectro de la enfermedad, de las cuales la fibrilación auricular (FA) es la más frecuente de todas. Debido a la heterogeneidad de la amiloidosis cardiaca, su incidencia real es desconocida, con lo que se denota un subdiagnóstico y en muchos casos estando oculta bajo la presentación de una enfermedad cardiaca habitual, lo que conlleva a una progresión silente de la misma y peores desenlaces. Se describe el caso clínico de un paciente con FA refractaria a cardioversión eléctrica y terapia ablativa en el contexto de amiloidosis cardiaca por transtirretina (ATTR) inicialmente inadvertida y descubierta como hallazgo incidental. El propósito de este reporte es revisar la asociación entre FA y ATTR, su epidemiología, fisiopatología, manifestación clínica, diagnóstico y tratamiento con el fin de ofrecer al personal médico herramientas para un diagnóstico oportuno de una enfermedad poco reconocida.

Abstract Cardiac amyloidosis is a disease characterized by the deposition of amyloid material in the extracellular matrix of the myocardium. Arrhythmias are part of the broad spectrum of the disease, with atrial fibrillation (AF) as the most common. Due to the heterogeneity of cardiac amyloidosis, its real incidence is unknown, denoting an underdiagnosis and in many cases being hidden under the presentation of a common heart disease, which leads to silent progression and worse outcomes. We describe the clinical case of a patient with AF refractory to electrical cardioversion and ablation therapy in the context of cardiac transthyretin amyloidosis (ATTR), initially unnoticed and found as an incidental diagnosis. The purpose of this report is to review the association between AF and ATTR, its epidemiology, pathophysiology, signs and symptoms, diagnosis and treatment in order to provide medical staff with tools for a timely diagnosis of a poorly recognized disease.

Prevalence of transthyretin amyloid cardiomyopathy in patients admitted for acute heart failure.

INTRODUCTION: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of AHF that benefits from a specific approach. The aim was to determine the prevalence of ATTR-CM among patients hospitalized for AHF. METHODS: A prospective study was conducted on consecutive patients aged 60 or older admitted for acute AHF without cardiogenic shock. RESULTS: The study included 103 patients, a total of 16 patients (15.5 %) were compatible with ATTR-CM. The ATTR-CM group showed a higher septal wall thickness (18.1 mm vs. 11.8 mm; P = 0.001), lower systolic excursion of the tricuspid annular plane (15 mm vs. 18.3 mm, P = 0.014), and S wave of the right ventricle (8 cm/s vs. 9.2 cm/s P=0.032). CONCLUSION: ATTR-CM is an underdiagnosed condition, there are some variables associated with its diagnosis. The coexistence with other comorbidities causing AHF, highlights the importance of considering screening for this cardiomyopathy in adults hospitalized for AHF.

¿Qué hay de nuevo en el diagnóstico de amiloidosis? / What is new in diagnosis of amyloidosis?

La amiloidosis siempre ha representado un desafío diagnóstico. En el año 2020, el Grupo de Estudio de Amiloidosis (GEA), confeccionó la Guía de Práctica Clínica para el Diagnóstico de Amiloidosis. Nuevas líneas de investigación se han desarrollado posteriormente. Esta revisión narrativa tiene como intención explorar el estado del arte en el diagnóstico de la amiloidosis. En pacientes con amiloidosis se recomienda la tipificación de la proteína mediante espectrometría de masa, técnica de difícil ejecución por requerir de microdisectores láser para la preparación de la muestra. Algunas publicaciones recientes proponen otros métodos para obtener la muestra de amiloide que se va a analizar, permitiendo prescindir de la microdisección. Por otra parte, en pacientes con Amiloidosis ATTR confirmada, la recomendación de secuenciar el gen amiloidogénico se encontraba destinada a los casos sospechosos de ATTR hereditaria (ATTRv,), pero actualmente esta se ha extendido a todos los pacientes sin importar la edad. En lo que respecta a los estudios complementarios orientados al diagnóstico de compromiso cardíaco, se ha propuesto el uso de la inteligencia artificial para su interpretación, permitiendo la detección temprana de la enfermedad y el correcto diagnóstico diferencial. Para el diagnóstico de neuropatía, las últimas publicaciones proponen el uso de la cadena ligera de neurofilamento sérica, que también podría resultar un indicador útil para seguimiento. Finalmente, con referencia a la amiloidosis AL, la comunidad científica se encuentra interesada en definir qué características determinan el carácter amiloidogénico de las cadenas livianas. La N-glicosilación de dichas proteínas impresiona ser uno de los determinantes en cuestión. (AU)

Amyloidosis has always represented a diagnostic challenge. In 2020, the Amyloidosis Study Group (ASG) developed the "Clinical Practice Guideline for the Diagnosis of Amyloidosis". New lines of research have subsequently emerged. This narrative review aims to explore the state of the art in the diagnosis of amyloidosis diagnosis. In patients with amyloidosis, protein typing by mass spectrometry is recommended, a technique hard to perform because it requires laser microdissection for sample preparation. Recent publications propose other methods to obtain the amyloid sample to be analyzed, making it possible to dispense with microdissection. On the other hand, in patients with confirmed TTR amyloidosis (aTTR), the recommendation to sequence the amyloidogenic gene was intended for suspected cases of hereditary aTTR but has now been extended to all patients regardless of age. (AU)

Manejo ambulatorio de pacientes con amiloidosis cardiaca por cadenas livianas / Outpatient management of patients with cardiac light chain amyloidosis

Resumen La amiloidosis primaria o de cadenas livianas (AL) es la forma más común de amiloidosis y se caracteriza por presentar una población clonal de células plasmáticas que producen una cadena ligera monoclonal de tipo lambda o kappa. En algunos sujetos, dicha cadena se deposita en forma de amiloide en los órganos y tejidos, dando lugar a manifestaciones clínicas, como proteinuria o síndrome nefrótico, miocardiopatía restrictiva y hepatomegalia. Aunque se considera una enfermedad rara, datos recientes sugieren que la amiloidosis cardíaca se subestima como una causa de enfermedades o síndromes cardíacos comunes. En la amiloidosis AL, tanto la respuesta hematológica como la de los órganos después del tratamiento son importantes para mejorar el resultado clínico, especialmente, si mejora la función cardíaca que es uno de los aspectos clave en el pronóstico de la amiloidosis AL. Se presenta el caso y la revisión de un paciente de sexo femenino, de 67 años de edad, que en la pesquisa diagnóstica de anemia e insuficiencia cardiaca (IC) se concluye en el diagnóstico de mieloma múltiple y amiloidosis cardiaca (AC) por depósito de cadenas livianas.

Abstract Primary or light chain (AL) amyloidosis is the most common form of amyloidosis and is characterized by a clonal population of plasma cells that produce a monoclonal lambda or kappa-type light chain, which in some subjects this chain is deposited as amyloid in the organs and tissues, giving rise to clinical manifestations such as proteinuria or nephrotic syndrome, restrictive cardiomyopathy and hepatomegaly. Although considered a rare disease, recent data suggest cardiac amyloidosis is underestimated as cause of common heart diseases or syndromes. In AL amyloidosis, both the hematologic and organ response after treatment, are important to improve clinical outcome. Especially if it improves cardiac function is one of the key aspects in the prognosis of AL amyloidosis. We present the case and review of a 67-year-old female patient, who in the investigation diagnoses anemia and heart failure concludes in the diagnosis of multiple myeloma and cardiac amyloidosis due to light chain deposition.

Aportes del ecocardiograma y las técnicas de deformación miocárdica en la amiloidosis cardíaca: bases de la técnica y hallazgos de utilidad diagnóstica / Contributions of echocardiography and myocardial deformation techniques in cardiac amyloidosis: basis of the technique and diagnostically useful findings / Contribuições da ecocardiografia e das técnicas de deformação miocárdica na amiloidose cardíaca: base da técnica e resultados diagnosticamente úteis

La amiloidosis cardíaca es una miocardiopatía restrictiva infiltrativa secundaria al depósito extracelular de amiloide. Las diferentes técnicas de imagen cardíaca permiten la evaluación de forma no invasiva. El ecocardiograma juega un rol central en la evaluación diagnóstica, pronóstica y ayuda a guiar el tratamiento. El objetivo de este artículo de revisión es describir las diferentes herramientas que nos brinda la ecocardiografía, poniendo énfasis en el strain por speckle tracking y describir su rol en el diagnóstico de esta patología.

Cardiac amyloidosis is an infiltrative restrictive cardiomyopathy secondary to extracellular amyloid deposition. Different cardiac imaging techniques allow noninvasive evaluation. Echocardiography plays a central role in diagnostic and prognostic evaluation and helps to guide treatment. The aim of this review is to describe the different tools provided by echocardiography, with emphasis on speckle tracking strain and to describe its role in the diagnosis of this pathology.

A amiloidose cardíaca é uma cardiomiopatia restritiva infiltrativa secundária ao depósito de amiloide extracelular. Diferentes técnicas de imagem cardíaca permitem fazer uma análise não invasiva. A ecocardiografia desempenha um papel central no diagnóstico e na avaliação prognóstica e ajuda a orientar o tratamento. O objetivo deste artigo de revisão é descrever as diferentes ferramentas proporcionadas pela ecocardiografia, com ênfase no strain por speckle tracking, e descrever o seu papel no diagnóstico desta patologia.

El electrocardiograma en la amiloidosis cardíaca: un arma para la sospecha diagnóstica de esta enfermedad / The electrocardiogram in cardiac amyloidosis: a weapon for the diagnosis suspect of this disease / O electrocardiograma na amiloidose cardíaca: uma arma para a suspeita diagnóstica desta doença

La amiloidosis cardíaca (AC) es una enfermedad con mal pronóstico si el tratamiento no se inicia de forma temprana, por lo que una de las asignaturas pendientes en esta enfermedad consiste en realizar un diagnóstico precoz. El electrocardiograma (ECG) es una prueba diagnóstica de bajo costo y amplia disponibilidad que nos permite sospechar esta enfermedad, dado que resulta normal en < 5% de los pacientes. El hallazgo clásico es la presencia de bajos voltajes en relación con la gran hipertrofia que se observa en las pruebas de imagen, así como el conocido patrón de pseudoinfarto. Ambos hallazgos son más frecuentes en el subtipo de amiloidosis por cadenas ligeras, que era el más frecuentemente diagnosticado en el pasado. Sin embargo, con la expansión del diagnóstico no invasivo del subtipo a transtiretina, su identificación ha crecido de forma exponencial y se convirtió en el más diagnosticado con más frecuencia en nuestro medio. Se debe prestar especial atención a todos estos hallazgos electrocardiográficos, con el fin de que esta prueba diagnóstica de sencilla obtención pueda contribuir de forma importante a la sospecha y al diagnóstico precoz de la AC.

Cardiac amyloidosis (CA) is a serious disease with a poor prognosis if treatment is not started early, so one of the pending issues in this condition is to make an early diagnosis. The electrocardiogram (EKG) is an inexpensive and widely available diagnostic test that can offer differential data when suspecting this disease, being normal in < 5% of these patients. The classic EKG finding is the presence of low voltages in relation to the large hypertrophy seen on imaging tests, as well as the well-known pseudoinfarct pattern. Both findings are more frequent in the light chain subtype of CA, which was the most frequently diagnosed in the past. However, with the growth of noninvasive diagnostic tests, the identification of the transtyretin subtype has grown exponentially, becoming the most frequently diagnosed in our setting. Special attention should be paid to all these electrocardiographic findings, so that this simple diagnostic test can make an important contribution to the early suspicion and diagnosis of CA.

A amiloidose cardíaca (AC) é uma doença grave com um mau prognóstico no caso de não se iniciar tratamento de forma precoce, pelo que a necessidade de um pronto diagnóstico é imperiosa. Quando se suspeita desta doença, o eletrocardiograma (ECG) é um teste de diagnóstico pouco dispendioso e disponível em todo o mundo, que pode fornecer dados discriminativos importantes, sendo normal em menos de 5% dos casos. O achado clássico do ECG é a presença de baixas voltagens em relação à grande hipertrofia vista na imagem, bem como o conhecido padrão de pseudoinfarte. Ambos os resultados são mais frequentes no subtipo a cadenas ligeras, o mais frequentemente diagnosticado no passado. No entanto, com o aumento dos testes de diagnóstico não-invasivos, o diagnóstico ddo subtipo a transtirretina, o mais cresceu de forma exponencial, tornando-se o mais frequentemente diagnosticado no nosso meio. Deve ser dada especial atenção a todos estes achados eletrocardiográficos já que esta prova de diagnóstico de fácil obtenção pode contribuir de forma importante para a suspeição de diagnóstico precoce de AC.

Aporte de la centellografía con trazadores tecneciados fosfatados al diagnóstico de amiloidosis cardíaca / Contribution of scintigraphy with technetium phosphated tracers to the diagnosis of cardiac amyloidosis / Contribuição da cintilografia com traçadores fosfatados com tecnécio para o diagnóstico de amiloidose cardíaca

Las amiloidosis son enfermedades causadas por el depósito patológico extracelular de un material proteico fibrilar e insoluble denominado amiloide, que puede estar vinculado a cadenas livianas (AL) o transtirretina (TTR). La amiloidosis cardíaca provoca una cardiomiopatía restrictiva de carácter progresivo caracterizada por falla cardíaca con función sistólica relativamente preservada, que se asocia a elevada mortalidad. Aunque el diagnóstico definitivo tradicionalmente se basa en la biopsia endomiocárdica, los avances en imagenología han mejorado su abordaje y la reciente introducción de terapias especificas permiten augurar cambios significativos en el pronóstico. El tratamiento difiere según el tipo de amiloide involucrado y su resultado depende de la instauración precoz de este, por lo cual resulta esencial un diagnóstico preciso y temprano. El centellograma cardíaco con fosfatos marcados (99mTc-PYP u otros), ampliamente disponible y de relativo bajo costo, se considera en la actualidad como una "biopsia molecular no invasiva" para el diagnóstico de la amiloidosis tipo ATTR, que debe ser usado en conjunto con la investigación de proteínas monoclonales en pacientes con sospecha clínica de la enfermedad.

Amyloidoses are diseases caused by the extracellular deposition of a fibrillar and insoluble protein material called amyloid, which can be linked either to light chains (AL) or transthyretin (TTR). Cardiac amyloidosis causes a progressive restrictive cardiomyopathy characterized by heart failure with relatively preserved systolic function, which is associated with high mortality. Although a definitive diagnosis is traditionally based on endomyocardial biopsy, advances in cardiac imaging have improved its approach, and the recent introduction of specific therapies predicts significant changes in prognosis. Since treatment differs according to the type of amyloid involved and the results depend on a prompt implementation, an accurate and early diagnosis is essential. Cardiac scintigraphy with labeled phosphates (99mTc-PYP or others), widely available and relatively inexpensive, is currently considered a "noninvasive molecular biopsy" for the diagnosis of ATTR type amyloidosis, which should be used in conjunction with investigation of monoclonal proteins in patients with clinical suspicion of the disease.

As amiloidoses são doenças causadas pela deposição patológica extracelular de um material proteico fibrilar e insolúvel, denominado amiloide, que pode estar ligado a cadeias leves (AL) ou transtirretina (TTR). A amiloidose cardíaca causa cardiomiopatia restritiva progressiva caracterizada por insuficiência cardíaca com função sistólica relativamente preservada, que está associada a alta mortalidade. Embora o diagnóstico definitivo seja tradicionalmente baseado na biópsia endomiocárdica, os avanços nos exames de imagem aprimoraram sua abordagem e a recente introdução de terapias específicas pode predizer mudanças significativas no prognóstico. O tratamento varia de acordo com o tipo de amiloide envolvida e seu resultado depende do início precoce, por isso um diagnóstico preciso e precoce é essencial. A cintilografia cardíaca com fosfatos marcados (99mTc-PYP ou outros), amplamente disponível e relativamente econômico, é atualmente considerada uma "biópsia molecular não invasiva" para o diagnóstico de amiloidose do tipo ATTR, que deve ser usada em conjunto com a investigação de proteínas monoclonais em pacientes com suspeita clínica da doença.

Primer uso de tafamidis en amiloidosis cardíaca TTR en Uruguay / First use of tafamidis in cardiac amyloidosis TTR in Uruguay / Primeiro uso de tafamidis em amiloidose cardíaca TTR no Uruguai

La amiloidosis cardíaca es una entidad con creciente reconocimiento, la variedad por transtiretina es la que más se diagnostica en la tercera edad de la vida. Hay reciente disponibilidad de fármacos que mejoran el pronóstico y la calidad de vida de los pacientes. Presentamos un caso de amiloidosis por transtiretina donde se usó por primera vez en nuestro país el fármaco tafamidis aprobado para el tratamiento de esta enfermedad.

Cardiac amyloidosis is an entity on increasing recognition, transthyretin variety is the most diagnosed in the third age. There is a recent availability of drugs that can improve the prognosis and quality of life of these patients. We present a case of transthyretin amyloidosis and the first use of tafamidis in our country.

A amiloidose cardíaca é uma entidade em crescente reconhecimento, a variedade transtiretina é a mais diagnosticada em idosos. Há disponibilidade recente de medicamentos que melhoram o prognóstico e a qualidade de vida dos pacientes. Apresentamos um caso de amiloidosis transteretina onde o medicamento tafamidis aprovado para esta doença foi utilizado pela primeira vez em nosso país.

Cardiomiopatía amiloídea por transtiretina: diagnóstico y manejo en la actualidad / Transthyretin amyloid cardiomyopathy: a review

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.

Amiloidosis cardíaca en un paciente con mieloma múltiple / Cardiac amyloidosis in a patient with multiple myeloma

Resumen La amiloidosis sistémica constituye una enfermedad poco frecuente, donde la infiltración cardíaca es la principal causa de morbimortalidad, sin importar la causa subyacente del depósito amiloide. Se reporta el caso de una paciente femenina de 48 años con síndrome nefrótico, insuficiencia cardíaca e inmunocompromiso, estableciéndose el diagnóstico de amiloidosis primaria con infiltración cardíaca secundaria a mieloma múltiple. Se discute brevemente la enfermedad, la importancia del juicio clínico apoyado en medios diagnósticos y los retos terapéuticos actuales.

Abstract Systemic amyloidosis constitutes a non common disease in which cardiac involvement is the leading cause of morbidity and mortality, regardless of the underlying pathogenesis of amyloid production. We present the case of a 48 years old female with nephrotic syndrome, heart failure and immunocompromise in which Primary Amyloidosis with cardiac involvement secondary to Multiple Myeloma is established as diagnosis. The disease is briefly discussed, as well as the value of clinical judgment supported on diagnostic means and the therapeutic challenges now days.

Miocardiopatía restrictiva poramiloidosis / Restrictive cardiomyopathy caused byamyloidosis

Resumen La miocardiopatía restrictiva es una presentación infrecuente de la amiloidosis y la forma más rara de las miocardiopatías. Hay depósito del amiloide en las paredes del corazón que limita su llenado y contribuye a largo plazo, a la insuficiencia cardiaca. Se presenta un caso, análisis de la fisiopatología, los métodos diagnósticos y su tratamiento.

Abstract Restrictive cardiomyopathy is an uncommon presentation of amyloidosis and the rarest form of cadiomyopathies. There is amyloid deposition on the heart walls that limit its filling and is a long-term contributing factor to heart failure. A case where pathophysiology analysis, diagnostic and treatments methods are analyzed is presented.

Bloqueo auriculoventricular completo como manifestación de amiloidosis cardiaca / Complete atrioventricular block as an evidence of amyloidosis

La amiloidosis cardiaca es una manifestación de un grupo de enfermedades sistémicas que se caracteriza por el mal plegamiento de proteínas que causa un depósito extracelular de la amiloide, conocido como amiloidosis. Es una causa importante de las enfermedades infiltrativas, que pueden ser responsables tanto del compromiso cardiaco como de otros órganos. Es importante el reconocimiento de su etiología primaria o secundaria para dar el tratamiento adecuado según su causa. Describimos un caso de un paciente de 69 años de edad, con amiloidosis que ingresa al servicio de urgencias con un bloqueo auriculoventricular completo.

Cardiac amyloidosis is a manifestation of a systemic diseases group characterized by protein misfolding caused by extracellular deposition of amyloid, known as amyloidosis. It is the main cause of infiltrative diseases that can be responsible of cardiac involvement as to other organs. It is important to recognize its primary or secondary etiology to give the appropriate treatment depending of the cause. We describe a case of a 69 year old patient with cardiac amyloidosis debuting in the emergency room with complete atrioventricular block.

Amiloidosis cardiaca por transtiretina: la gammagrafía mostró el camino / Transthyretin amyloidosis: Scintigraphy showing the way

Fundamento y objetivo: La amiloidosis cardiaca es una enfermedad grave producida por el depósito extracelular a nivel cardiaco de diversas sustancias que se identifican con el análisis de una biopsia endomiocárdica, técnica invasiva, poco accesible y de difícil interpretación. Debido a que las diversas entidades suponen diferente evolución, tratamiento y pronóstico, tiene gran relevancia clínica conocer el subtipo de esta patología. El objetivo es presentar diferentes técnicas diagnósticas no invasivas que nos puedan orientar a sospechar la amiloidosis por transtiretina. Método: Con este caso clínico reflejamos tanto la dificultad para llegar al diagnóstico del subtipo de amiloidosis como la utilidad de las pruebas radiológicas, la gammagrafía y la cardiorresonancia, en el diagnóstico diferencial de amiloidosis cardiaca. Resultados: El intenso depósito cardiaco de forma biventricular en la gammagrafía cardiaca con 99mTc-DPD como el realce tardío biventricular circunferencial en la cardiorresonancia son herramientas muy útiles para orientar hacia el diagnóstico de la amiloidosis por transtiretina.

Background and objetive: Cardiac amyloidosis is a very severe disease caused by extracellular deposition of insoluble fibrils. The gold standard for diagnosing cardiac amyloidosis is an endomyocardial biopsy. This technique is invasive, limited to experienced centers, and thus not widely available. It is required to perform special techniques to precisely determine the amyloid type as the treatment, evolution and prognosis of the disease differs greatly according the type of amyloid present. Method: In this case report we want to present the difficulties for diagnosing the types of amyloid involved in cardiac amyloidosis as well as the usefulness of cardiac MRI for diagnosing cardiac amyloidosis, particularly when performed with the use of the gadolinium as an imaging agent. Results: Biventricular, concentric late gadolinium enhancement on cardiac magnetic resonance and on technetium pyrophosphate scan (99mTc-DPD) showed to be helpful in the diagnosis of senile cardiac amyloidosis transthyrenin variant.

Amiloidosis cardíaca: a propósito de un caso / Case report: cardiac amyloidosis

La amiloidosis corresponde a un conjunto de enfermedades que tienen en común el depósito de amiloide en uno o más órganos. El hallazgo típico del compromiso cardíaco secundario a la amiloidosis es la presencia de insuficiencia cardíaca rápidamente progresiva. La historia natural de esta enfermedad en ausencia de tratamiento es de un rápido compromiso con alta mortalidad. Reportamos el caso de una paciente con esta enfermedad, describiendo su historia, manejo y seguimiento.

Cardiac amyloidosis refers to a set of diseases characterized by amyloid deposit in one or more organs. The typical finding of cardiac involvement secondary to amyloidosis is the presence of rapidly progressive heart failure. The natural story of this disease in the absence of treatment leads to rapid deterioration with a high mortality rate We report the case of a patient with amyloidosis and cardiac invol-vement, describing the clinical history, management and follow up.