Cardiac magnetic resonance-feature tracking technique can assess cardiac function and prognosis in patients with myocardial amyloidosis / 南方医科大学学报

OBJECTIVE@#To quantitatively assess cardiac functions in patients with cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance-feature tracking (CMR-FT) technique and evaluate the prognostic value of CMR-FT in patients with CA.@*METHODS@#We retrospectively collected the data from 31 CA patients with systemic amyloidosis confirmed by Congo red staining and serum immunohistochemistry after extracardiac tissue biopsy undergoing CMR at our hospital from March, 2013 to June, 2021.Thirty-one age and gender matched patients with asymmetric left ventricular wall hypertrophy and 31 healthy individuals without organic or functional heart disease served as the controls.Radial, circumferential and longitudinal strains and strain rates of the left ventricle at the global level and in each myocardial segment (basal, middle and apical) were obtained with CMR-FT technique and compared among the 3 groups.The predictive value of myocardial strains and strain rates for all-cause mortality in CA patients was analyzed using a stepwise COX regression model.@*RESULTS@#The left ventricular volume, myocardial mass, ejection fraction and cardiac output differed significantly among the groups (P < 0.05).Except for apical longitudinal strain, the global and segmental strains were all significantly lower in CA group than in HCM group (P < 0.05).The global and segmental strains were all significantly lower in CA group than in the healthy individuals (P < 0.05).The basal strain rates in the 3 directions were significantly lower in CA group than in the healthy individuals (P < 0.05), but the difference in apical strain rates was not statistically significant between the two groups.Multivariate stepwise COX analysis showed that troponin T (HR=1.05, 95%CI: 1.01-1.10, P=0.017) and middle peak diastolic circumferential strain rate (HR=6.87, 95%CI: 1.52-31.06, P=0.012) were strong predictors of death in CA patients.@*CONCLUSION@#Strain and strain rate parameters derived from CMR-FT based on cine sequences are new noninvasive imaging markers for assessing cardiac impairment in CA and cardiac function changes in HCM, and provide independent predictive information for all-cause mortality in CA patients.

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.

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.

Estudio de la amiloidosis cardíaca por cardiorresonancia / Cardiac amyloidosis study by cardioresonance / Estudo da amiloidose cardíaca por cardiorressonância

Dada su epidemiología, la amiloidosis cardíaca se ha vuelto un desafío diagnóstico del siglo XXI. La resonancia cardíaca se ha transformado en una herramienta diagnóstica y pronóstica fundamental en la práctica clínica diaria. En este artículo de revisión resumimos el conocimiento, primero abordando la técnica en sí, desde protocolos generales a específicos para su diagnóstico. Posteriormente, y tomando estas herramientas, sistematizamos la utilidad diagnóstica, pronóstica y terapéutica, con base en la practicidad y evidencia científica más recientes, otorgando la posibilidad de utilizar y abordar desde un correcto diagnóstico por imagen diferentes aspectos de esta enfermedad prevalente.

Given its epidemiology, cardiac amyloidosis has become a diagnostic challenge of the twenty-first century. Cardiac resonance has become a fundamental diagnostic and prognostic tool in daily clinical practice. In this review article we summarize the knowledge, first addressing the technique itself, from general to specific protocols for its diagnosis. Subsequently, and taking this tool we systematize the diagnostic, prognostic, and therapeutic utility, based on the most recent practicality and scientific evidence, granting the possibility of using and addressing from a correct diagnostic imaging different aspect of this prevalent disease.

Dada a sua epidemiologia, a amiloidose cardíaca tornou-se um desafio do século XXI. A ressonância cardíaca tornou-se uma ferramenta diagnóstica e prognóstico fundamental na prática clínica diária. Neste artigo de revisão resumimos primeiro o conhecimento abordando a própria técnica, desde protocolos gerais até específicos para seu diagnóstico. Posteriormente, e tomando essa ferramenta sistematizamos a utilidade diagnóstica, prognóstica e terapêutica, com base na praticidade e evidência científica mais recentes, concedendo a possibilidade de utilização e abordagem de uma imagem diagnóstica correta de diferentes aspectos desta doença prevalente.

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.

Perfil Clínico, Laboratorial e de Métodos de Imagem na Amiloidose Sistêmica em um Centro de Referência Cardiológico Brasileiro / Clinical, Laboratory, and Imaging Profile in Patients with Systemic Amyloidosis in a Brazilian Cardiology Referral Center

Resumo Fundamento Amiloidose sistêmica é uma doença com manifestações clínicas diversas. O diagnóstico envolve suspeita clínica, aliada a métodos complementares. Objetivo Descrever o perfil clínico, laboratorial, eletrocardiográfico e de imagem no acometimento cardíaco da amiloidose sistêmica. Métodos Estudo de uma amostra de conveniência, analisando dados clínicos, laboratoriais, eletrocardiográficos, ecocardiográficos, medicina nuclear e ressonância magnética. Considerou-se significância estatística quando p < 0,05. Resultados Avaliaram-se 105 pacientes (com mediana de idade de 66 anos), sendo 62 homens, dos quais 83 indivíduos apresentavam amiloidose por transtirretina (ATTR) e 22 amiloidose por cadeia leve (AL). Na ATTR, 68,7% eram de caráter hereditário (ATTRh) e 31,3% do tipo selvagem (ATTRw). As mutações mais prevalentes foram Val142Ile (45,6%) e Val50Met (40,3%). O tempo de início dos sintomas ao diagnóstico foi 0,54 e 2,15 anos nas formas AL e ATTR (p < 0,001), respectivamente. O acometimento cardíaco foi observado em 77,9% dos ATTR e 90,9% dos AL. Observaram-se alterações de condução atrioventricular em 20% e intraventricular em 27,6% dos pacientes, sendo 33,7 % na ATTR e 4,5% das AL (p = 0,006). A forma ATTRw apresentou mais arritmias atriais que os ATTRh (61,5% x 22,8%; p = 0,001). Ao ecocardiograma a mediana da espessura do septo na ATTRw x ATTRh x AL foi de 15 mm x 12 mm x 11 mm (p = 0,193). Observou-se BNP elevado em 89,5% dos indivíduos (mediana 249 ng/mL, IQR 597,7) e elevação da troponina em 43,2%. Conclusão Foi possível caracterizar, em nosso meio, o acometimento cardíaco na amiloidose sistêmica, em seus diferentes subtipos, através da história clínica e dos métodos diagnósticos descritos.

Abstract Background Systemic amyloidosis is a disease with heterogeneous clinical manifestations. Diagnosis depends on clinical suspicion combined with specific complementary methods. Objective To describe the clinical, laboratory, electrocardiographic, and imaging profile in patients with systemic amyloidosis with cardiac involvement. Methods This study was conducted with a convenience sample, analyzing clinical, laboratory, electrocardiographic, echocardiographic, nuclear medicine, and magnetic resonance data. Statistical significance was set at p < 0.05. Results A total of 105 patients were evaluated (median age of 66 years), 62 of whom were male. Of all patients, 83 had transthyretin (ATTR) amyloidosis, and 22 had light chain (AL) amyloidosis. With respect to ATTR cases, 68.7% were the hereditary form (ATTRh), and 31.3% were wild type (ATTRw). The most prevalent mutations were Val142Ile (45.6%) and Val50Met (40.3%). Time from onset of symptoms to diagnosis was 0.54 and 2.15 years, in the AL and ATTR forms, respectively (p < 0.001). Cardiac involvement was observed in 77.9% of patients with ATTR and in 90.9% of those with AL. Alterations were observed in atrioventricular and intraventricular conduction in 20% and 27.6% of patients, respectively, with 33.7% in ATTR and 4.5% in AL (p = 0.006). In the ATTRw form, there were more atrial arrhythmias than in ATTRh (61.5% versus 22.8%; p = 0.001). On echocardiogram, median septum thickness in ATTRw, ATTRh, and AL was 15 mm, 12 mm, and 11 mm, respectively (p = 0.193). Elevated BNP was observed in 89.5% of patients (median 249, ICR 597.7), and elevated troponin was observed in 43.2%. Conclusion In this setting, it was possible to characterize cardiac involvement in systemic amyloidosis in its different subtypes by means of clinical history and the diagnostic methods described.

Value of (11)C-PiB PET/MRI in the evaluation of organ involvement in primary systemic light chain amyloidosis / 中华血液学杂志

Objective: To analyze the value of (11)C-PiB PET/MRI for evaluating organ involvement in patients with primary light chain amyloidosis (pAL) . Methods: The clinical data of 20 patients with pAL and 3 healthy volunteers from January 2019 to October 2021 were retrospectively analyzed. The correlation between the organ involvement evaluated by clinical standards and PET/MRI was compared. The relationship between cardiac-related biological indicators, disease stage, and the maximum standardized uptake value (SUVmax) were analyzed. The relationship between 24-hour urinary protein quantification and kidney SUVmax was analyzed. Results: ①In 20 patients (18 newly diagnosed patients and 2 non-newly diagnosed patients) ,(11)C-PiB positive uptake was observed in the heart (15 patients, 75%) , lung (8 patients, 40%) , bone marrow (10 patients, 50%) , muscle (10 patients, 50%) , tongue muscle (7 patients, 35%) , thyroid (6 patients, 30%) , salivary gland (4 patients, 20%) , spleen (2 patients, 10%) , and stomach wall (1 patient, 5%) . ②Organ involvement on (11)C-PiB PET/MRI showed good correlations with the clinical evaluation criteria for the heart and bone marrow. The positive rate of PET/MRI evaluation in the lung, spleen, gland, muscle, and tongue muscle was significantly higher than the clinical criteria. However, (11)C-PiB PET/MRI has limitations in the evaluation of the nervous system and fat tissue. ③To analyze the relationship between cardiac-related biological indexes and the SUVmax of the heart in 13 newly diagnosed patients. Patients with left ventricular ejection fraction (LVEF) <50% and interventricular septal thickness (ISV) ≥1.2 cm showed a higher SUVmax than patients with LVEF ≥50% and ISV<1.2 cm (P<0.05) .There are significant differences in the SUVmax of the heart between the Mayo2004 stage and the Mayo2012 stage. The later the disease stage, the higher the SUVmax (P<0.05) . The SUVmax of the heart was positively correlated with cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (P<0.01) .There was no significant correlation between renal SUVmax and 24-hour urine protein (P>0.05) . Conclusion: Whole body (11)C-PiB PET/MRI, as a visualization system of amyloid protein, is used to qualitatively evaluate organ involvement, which can improve the level of early non-invasive diagnosis. Whole body (11)C-PiB PET/MRI can be used to perform quantitative evaluation of organ levels, especially the heart, which is expected to evaluate organ function and predict disease prognosis more accurately.

Amiloidosis cardiaca secundaria a macroglobulinemia de Waldenström / Cardiac amyloidosis secondary to Waldenström macroglobulinemia

Introducción: La macroglobulinemia de Waldenström constituye una neoplasia hematológica del grupo de las gammapatías monoclonales, que incluye síntomas sistémicos y relacionados al incremento de la paraproteína M. Objetivo: Describir un caso de amiloidosis cardiaca asociada a macroglobulinemia. Caso clínico: Paciente masculino que fue admitido por astenia, disfonía, y durante su evolución desarrolló disnea progresiva, insuficiencia cardiaca y efusión pleural. Adicionalmente, la ecocardiografía mostró patrón granular miocárdico, y la biopsia pleural resultó positiva para la tinción rojo congo. Posteriormente, recibió tratamiento con bortezomib, dexametasona y rituximab con evolución favorable. Conclusiones: En esta enfermedad el diagnóstico temprano es una ventaja importante para la supervivencia. Es por esa razón, que su manejo es paliativo de las manifestaciones cardiacas. El presente caso pone en manifiesto un reto diagnóstico, en el cual se deben tomar en cuenta las etiologías menos frecuentes de insuficiencia cardiaca(AU)

Introduction: Waldenström's macroglobulinemia is a hematological neoplasm belonging to the group of monoclonal gammopathies, which includes systemic symptoms and those related to an increase in M paraprotein. Objective: To describe a case of cardiac amyloidosis associated with macroglobulinemia. Clinical case: Male patient who was admitted for asthenia, dysphonia, and who, during his evolution, developed progressive dyspnea, heart failure and pleural effusion. Additionally, echocardiography showed myocardial granular pattern, while pleural biopsy was positive for Congo red staining. Subsequently, he received treatment with bortezomib, dexamethasone and rituximab, with favorable evolution. Conclusions: In this disease, early diagnosis is an important advantage for survival. Therefore, its management is palliative of cardiac manifestations. The present case shows a diagnostic challenge, in which the less frequent etiologies of heart failure must be taken into account(AU)

Amiloidosis cardiaca: estudio de caso y revisión bibliográfica / Cardiac amyloidosis: Case study and bibliographic review

Resumen La amiloidosis es una enfermedad multisistémica, originada por un plegamiento proteico anormal el cual a su vez genera su depósito y acumulación en diferentes tejidos. A nivel cardiovascular, el amiloide se deposita en el tejido miocárdico generando las manifestaciones típicas de la enfermedad. Presenta hallazgos electrocardiográficos y ecocardiográficos distintivos que proporcionan una ayuda invaluable en el diagnóstico de la amiloidosis cardiaca. En el presente artículo se expone un caso de un paciente portador de amiloidosis AL, quien exhibe síntomas de falla cardiaca y en el cual se documenta posteriormente severo compromiso cardiovascular. Además, se presenta una revisión de las manifestaciones cardiovasculares y el diagnóstico de dicha patología.

Abstract Amyloidosis is a multisystemic disease, originated by an abnormal protein folding which in turn generates its deposit and accumulation in different tissues. At a cardiovascular level, amyloid is deposited in the myocardial tissue and thus generating the typical manifestations of the disease. It presents distinctive electrocardiographic and echocardiographic findings that provide invaluable help in the diagnosis of cardiac amyloidosis. In this article, a case of a patient with AL amyloidosis is presented. Said patient developed symptoms of heart failure, which later progressed into severe cardiovascular compromise. Furthermore, a review of the cardiovascular manifestations and the diagnosis of said pathology is presented.

Centellografía con fosfonatos para el diagnóstico de la amiloidosis cardíaca por transtirretina / Bone seeking tracers' scintigraphy for the diagnosis of transthyretin cardiac amyloidosis

La amiloidosis cardíaca del subtipo transtirretina (ATTR) es una cardiopatía restrictiva que causa insuficiencia cardíaca en un número considerable de pacientes. Su identificación temprana permitiría brindar tratamientos específicos. Sin embargo, el diagnóstico de ATTR es complejo y requiere métodos invasivos. Los fosfonatos marcados con 99mTecnecio han demostrado ser útiles para el diagnóstico, aunque en Argentina la experiencia es escasa. Nuestro objetivo fue evaluar la utilidad de este método para diagnosticar de forma no invasiva la ATTR. Se estudiaron 46 pacientes entre septiembre de 2016 y enero de 2018 por sospecha de amiloidosis cardíaca. Se evaluó el grado de captación cardíaca con relación al tejido óseo, a la hora, mediante dos métodos: semi-cuantitativo y cuantitativo. El diagnóstico definitivo de amiloidosis y el subtipo específico fue asignado por el centro de miocardiopatías de nuestra institución siguiendo recomendaciones internacionales. Una captación ≥ grado II presentó un valor predictivo positivo del 96% y negativo del 100% para el diagnóstico de amiloidosis cardíaca ATTR. El valor de corte de 1.38 en la relación corazón/pulmón presentó una sensibilidad del 96% y una especificidad del 100% para discriminar entre pacientes con ATTR de aquellos con amiloidosis por cadenas livianas u otras afecciones (área bajo la curva relación corazón/pulmón = 0.95 p < 0.001). La centellografía con fosfonatos marcados demostró ser un método no invasivo útil para diagnosticar ATTR. Dado que además de ser no invasiva, es una herramienta de bajo costo y ampliamente disponible en nuestro medio, su aplicación puede redundar en un beneficio clínico para muchos pacientes.

Transthyretin cardiac amyloidosis (ATTR) is a restrictive cardiomyopathy that leads to heart failure in considerable number of patients. Early diagnosis allows specific treatment options. However, ATTR diagnosis is complex and requires invasive procedures. The utility of 99mTc-phosphate tracers for non-invasive diagnosis is well-known but the experience in Argentina is insufficient. The aim of this work was to assess the utility of 99mTc-phosphate tracers for the diagnosis of ATTR. A total of 46 scintigraphies for detection of cardiac amyloidosis performed between September 2016 and January 2018 were analyzed. Cardiac retention after one hour was assessed in relation to bone uptake using two methods: A semi-quantitative visual score (grade 0 = absent, I = low II = moderate-III = high) and a quantitative method (heart/lung ratio). The final diagnosis and the amyloidosis subtype were carried out by our institution cardiomyopathy team according to international guidelines. The positive and negative predictive values for Grade ≥ II were 96% and 100% respectively for diagnosis of ATTR. Using 1.38 as cut-off value for heart/lung ratio the sensitivity and the specificity were 96% and 100%, respectively for differentiating transthyretin cardiac amyloidosis from light-chain cardiac amyloidosis and other cardiopathies. Scintigraphy with 99mTc-phosphate tracers enable noninvasive diagnosis and subtype classification of cardiac amyloidosis. The use of this non-invasive, inexpensive and widely available tool will result in better patient management.

Light chain cardiac amyloidosis - a rare cause of heart failure in a young adult

SUMMARY Cardiac amyloidosis is an infiltrative cardiomyopathy, resulting from amyloid deposition within the myocardium. In primary systemic (AL-type) amyloidosis, the amyloid protein is composed of light chains resulting from plasma-cell dyscrasia, and cardiac involvement occurs in up to 50% of the patients We present a case of a 43-year-old man, with complaints of periodical swollen tongue and xerostomia, bleeding gums and haematuria for two months. His blood results showed normocytic anaemia, thrombocytopenia and a high spontaneous INR, therefore he was referred to the Internal Medicine clinic. In the first visit, he showed signs and symptoms of overt congestive heart failure and was referred to the emergency department. The electrocardiogram showed sinus tachycardia and low voltage criteria. Echocardiography showed biventricular hypertrophy with preserved ejection fraction, restrictive physiology with elevated filling pressures, thickened interatrial septum and atrioventricular valves, small pericardial effusion and relative "apical sparing" on 2D longitudinal strain. Cardiac MRI showed diffuse subendocardial late enhancement. Serum protein electrophoresis was inconclusive, however urine analysis revealed nephrotic range proteinuria, positive Bence Jones protein and an immunofixation test with a monoclonal lambda protein band. Abdominal fat biopsy was negative for Congo red stain, nevertheless a bone marrow biopsy was performed, revealing lambda protein monoclonal plasmocytosis, confirming the diagnosis of primary systemic amyloidosis. This case represents a rare cause of heart failure in a young adult. Low-voltage QRS complexes and typical echocardiography features should raise the suspicion for cardiac amyloidosis. Prognosis is dictated by the level of cardiac involvement; therefore, early diagnosis and treatment are crucial.

RESUMO A amiloidose cardíaca corresponde a uma miocardiopatia infiltrativa, resultante do depósito da proteína amiloide no miocárdio. Na amiloidose sistêmica primária (tipo AL), a proteína amiloide é composta por cadeias leves que resultam de discrasia dos plasmócitos, havendo envolvimento cardíaco em até 50% dos doentes. Apresentamos o caso de um homem de 43 anos, com queixas de edema periódico da língua e xerostomia, hemorragia gengival e hematúria há dois meses. Analiticamente havia a destacar anemia normocítica, trombocitopenia e um INR alto espontâneo, pelo que foi referenciado à consulta de Medicina Interna. Na primeira consulta, apresentou-se com sinais de insuficiência cardíaca congestiva franca, pelo que foi referenciado ao Serviço de Urgência. O eletrocardiograma demonstrou taquicardia sinusal e critérios de baixa voltagem. O ecocardiograma revelou hipertrofia biventricular com fração de ejeção preservada, fisiologia restritiva com elevação das pressões de enchimento, espessamento do septo interauricular e das válvulas auriculoventriculares, derrame pericárdico ligeiro e padrão de apical sparing no strain longitudinal 2D. Realizou ainda ressonância magnética cardíaca, que mostrou realce tardio subendocárdico difuso. A eletroforese das proteínas foi inconclusiva, contudo a análise da urina revelou proteinúria no espectro nefrótico, presença de proteína de Bence Jones e um teste de imunofixação com uma banda monoclonal de cadeias lambda. A biópsia da gordura abdominal foi negativa. Não obstante, foi realizada uma biópsia da medula óssea, verificando-se plasmocitose monoclonal lambda, o que confirmou o diagnóstico de amiloidose primária sistêmica. Este caso representa uma causa rara de insuficiência cardíaca no jovem adulto. A baixa voltagem no eletrocardiograma e os achados ecocardiográficos típicos devem fazer suspeitar de amiloidose cardíaca. O prognóstico é ditado pelo nível de envolvimento cardíaco, motivo pelo qual o diagnóstico e o tratamento precoces são essenciais.

Right Atrial Deformation Analysis in Cardiac Amyloidosis - Results from the Three-Dimensional Speckle-Tracking Echocardiographic MAGYAR-Path Study / Análise da Deformação Atrial Direita na Amiloidose Cardíaca - Resultados de Ecocardiografia Tridimensional de Speckle-Tracking do Estudo MAGYAR-Path

Abstract Background: Light-chain (AL) cardiac amyloidosis (CA) is characterized by fibril deposits, which are composed of monoclonal immunoglobulin light chains. The right ventricle is mostly involved in AL-CA and impairment of its function is a predictor of worse prognosis. Objectives: To characterize the volumetric and functional properties of the right atrium (RA) in AL-CA by three-dimensional speckle-tracking echocardiography (3DSTE). Methods: A total of 16 patients (mean age: 64.5 ± 10.1 years, 11 males) with AL-CA were examined. Their results were compared to that of 15 age- and gender-matched healthy controls (mean age: 58.9 ± 6.9 years, 8 males). All cases have undergone complete two-dimensional Doppler and 3DSTE. A two-tailed p value of less than 0.05 was considered statistically significant. Results: Significant differences could be demonstrated in RA volumes respecting cardiac cycle. Total (19.2 ± 9.3% vs. 27.9 ± 10.7%, p = 0.02) and active atrial emptying fractions (12.1 ± 8.1 vs. 18.6 ± 9.8%, p = 0.05) were significantly decreased in AL-CA patients. Peak global (16.7 ± 10.3% vs. 31.2 ± 19.4%, p = 0.01) and mean segmental (24.3 ± 11.1% vs. 38.6 ± 17.6%, p =0.01) RA area strains, together with some circumferential, longitudinal and segmental area strain parameters, proved to be reduced in patients with AL-CA. Global longitudinal (4.0 ± 5.2% vs. 8.2 ± 5.5%, p = 0.02) and area (7.8 ± 8.1% vs. 15.9 ± 10.3%, p = 0.03) strains at atrial contraction and some circumferential and area strain parameters at atrial contraction were reduced in AL-CA patients. Conclusion: Significantly increased RA volumes and deteriorated RA functions could be demonstrated in AL-CA.

Resumo Fundamento: A amiloidose cardíaca (AC) de cadeias leves (AL) é caracterizada por depósitos fibrilares, que são compostos por cadeias leves de imunoglobulina monoclonal. O ventrículo direito é mais afetado pela AC-AL, e o comprometimento da sua função é preditor de um prognóstico pior. Objetivos: Caracterizar as propriedades volumétricas e funcionais do átrio direito (AD) na AC-AL por ecocardiografia tridimensional de speckle-tracking (3DSTE). Métodos: Um total de 16 pacientes (idade média: 64,5 ± 10,1 anos, 11 homens) com AC-AL foram examinados. Seus resultados foram comparados aos de 15 controles saudáveis pareados por idade e gênero (média de idade: 58,9 ± 6,9 anos, 8 homens). Todos os casos foram submetidos a Doppler bidimensional completo e 3DSTE. Um valor p bicaudal inferior a 0,05 foi considerado estatisticamente significativo. Resultados: Diferenças significativas foram demonstradas em volumes do AD com respeito ao ciclo cardíaco. O total (19,2 ± 9,3% vs. 27,9 ± 10,7%, p = 0,02) e as frações ativas de esvaziamento atrial (12,1 ± 8,1 vs. 18,6 ± 9,8%, p = 0,05) foram significativamente menores nos pacientes com AC-AL. Picos de strain no AD em áreas globais (16,7 ± 10,3% vs. 31,2 ± 19,4%, p = 0,01) e segmentares médias (24,3 ± 11,1% vs. 38,6 ± 17,6%, p = 0,01), juntamente com alguns parâmetros de strain por áreas circunferenciais, longitudinais e segmentares, mostraram-se menores em pacientes com AC-AL. Strains globais longitudinais (4,0 ± 5,2% vs. 8,2 ± 5,5%, p = 0,02) e por área (7,8 ± 8,1 vs. 15,9 ± 10,3%, p = 0,03) na contração atrial e alguns parâmetros de circunferência e de strain por área na contração atrial foram menores em pacientes com AC-AL. Conclusão: Foi possível demonstrar o aumento significativo dos volumes do AD e a deterioração de suas funções na AC-AL.

Isolated primary amyloidosis of the inferior rectus muscle mimicking Graves’ orbitopathy / Amiloidose primária isolada do músculo reto inferior simulando orbitopatia de Graves

ABSTRACT The diagnosis of Graves’ orbitopathy is usually straightforward. However, orbital diseases that mimick some clinical signs of Graves’ orbitopathy may cause diagnostic confusion, particularly when associated to some form of thyroid dysfunction. This report describes the rare occurrence of localized inferior rectus muscle amyloidosis in a patient with autoimmune hypothyroidism, who was misdiagnosed as Graves’ orbitopathy. A 48-year-old man complained of painless progressive proptosis on the left side and intermittent vertical diplopia for 6 months. The diagnosis of Graves’ orbitopathy was entertained after magnetic resonance imaging revealing a markedly enlarged, tendon-sparing inferior rectus enlargement on the left side, and an autoimmune hypothyroidism was disclosed on systemic medical workup. After no clinical improvement with treatment, the patient was referred to an ophthalmologist and further investigation was performed. The presence of calcification in the inferior rectus muscle on computed tomography, associated with the clinical findings led to a diagnostic biopsy, which revealed amyloid deposition. This report emphasizes that a careful evaluation of atypical forms of Graves’ orbitopathy may be crucial and should include, yet with rare occurrence, amyloidosis in its differential diagnosis.

RESUMO O diagnóstico de orbitopatia de Graves usualmente é fácil de ser estabelecido. No entanto, doenças da órbita que simulam alguns sinais clínicos da orbitopatia de Graves podem levar à confusão diagnóstica, particularmente quando associada à alguma forma de disfunção tireoidiana. Relatamos a ocorrência rara de amiloidose localizada no músculo reto inferior em paciente com hipotireoidismo autoimune, que recebeu inicialmente o diagnóstico errôneo de orbitopatia de Graves. Paciente masculino, 48 anos, com queixa de proptose progressiva e indolor do lado esquerdo e diplopia vertical intermitente há 6 meses. O diagnóstico de orbitopatia de Graves foi considerado após a realização de ressonância magnética, que revelou aumento importante do músculo reto inferior esquerdo, sem acometimento do tendão, e uma propedêutica sistêmica detectou hipotireoidismo autoimune. Como não houve melhora com o tratamento clínico, o paciente foi encaminhado a um oftalmologista, que realizou nova investigação. A presença de calcificação no músculo reto inferior na tomografia computadorizada, associada aos achados clínicos, levou a uma biópsia da lesão, que demonstrou a deposição de material amiloide. Este relato enfatiza como uma avaliação minuciosa das formas atípicas de orbitopatia de Graves é essencial e deve incluir a ocorrência, embora rara, de amiloidose no diagnóstico diferencial da orbitopatia de Graves.

Resonancia magnética en el diagnóstico de amiloidosis cardíaca / Magnetic resonance imaging in the diagnosis of cardiac amyloidosis

La resonancia magnética cardíaca (RMC) es un método no invasivo que provee información acerca de la anatomía, función y caracterización tisular del miocardio, llegando a ser de gran utilidad en el diagnóstico y diferenciación de trastornos infiltrativos como la amiloidosis. La amiloidosis cardíaca (AC) es una miocardiopatía restrictiva resultado del depósito de amiloide en el corazón, que determina una semiología característica en la RM que permite establecer el diagnóstico en la mayoría de los casos. Los hallazgos por RMC incluyen hipertrofia miocárdica del ventrículo izquierdo (HVI) con realce tardío positivo en el ventrículo izquierdo (VI) y el resto de las cámaras cardíacas, asociado a alteración en la cinética del gadolinio con anulación del pool sanguíneo y hallazgos adicionales, como derrame pleural o pericárdico o ambos, que apoyan el diagnóstico1-3. Presentamos el caso de una paciente con diagnóstico de amiloidosis sometida a RMC en donde se demuestran los hallazgos característicos de esta patología. (AU)

Cardiac magnetic resonance imaging (MRI) is a noninvasive method of image that provides information about the anatomy, function and tissue characterization, becoming very useful in the diagnosis and differentiation of infiltrative disorders such as amyloidosis. Cardiac amyloidosis (CA) is a restrictive cardiomyopathy result of amyloid deposition in the heart. MRI findings include myocardial hypertrophy with positive late gadolinium enhancement (LGE) in the left ventricle (LV) associated with the altered kinetics of gadolinium and additional findings as pleural and pericardial effusion that support the diagnosis. We report the case of a patient diagnosed with amyloidosis showing the characteristic MR findings in this pathology. (AU)

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.