Clinical suspicion, diagnosis and management of cardiac amyloidosis: update document and executive summary.

In recent years, the interest in cardiac amyloidosis has grown exponentially. However, there is a need to improve our understanding of amyloidosis in order to optimise early detection systems. Therefore, it is crucial to incorporate solutions to improve the suspicion, diagnosis and follow-up of cardiac amyloidosis. In this sense, we designed a tool following the different phases to reach the diagnosis of cardiac amyloidosis, as well as an optimal follow-up: a) clinical suspicion, where the importance of the "red flags" to suspect it and activate the diagnostic process is highlighted; 2) diagnosis, where the diagnostic algorithm is mainly outlined; and 3) follow-up of confirmed patients. This is a practical resource that will be of great use to all professionals caring for patients with suspected or confirmed cardiac amyloidosis, to improve its early detection, as well as to optimise its accurate diagnosis and optimal follow-up.

Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL) / Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis

Introducción y objetivos: La amiloidosis cardiaca (AC) es una patología asociada a un elevado número de ingresos hospitalarios. Dada la escasa información disponible al respecto, planteamos un análisis de la incidencia y las causas de hospitalización en esta enfermedad.Material y métodosSe evaluaron 143 pacientes (128 por transtiretina [AC-ATTR] y 15 por cadenas ligeras [AC-AL]) incluidos en el Registro de Amiloidosis Cardiaca de Galicia (AMIGAL), recogiendo todas sus hospitalizaciones.ResultadosDurante un seguimiento mediano de 959 días se produjeron 179 hospitalizaciones no programadas (tasa de incidencia [TI] 512,6 ingresos hospitalarios por 1.000 pacientes-año), siendo las más habituales las de causa cardiovascular (n=109, TI 312,2). El motivo individual de ingreso hospitalario más frecuente fue la insuficiencia cardiaca (IC) (n=87, TI 249,2).La AC-AL se asoció con una TI de hospitalizaciones no programadas más elevada que la AC-ATTR (TI 781 vs. 483,2; HR 1,62; p=0,029) a expensas de las de causa no cardiovascular (TI 376 vs. 181,2; HR 2,07; p=0,027). La supervivencia libre de hospitalización no programada al año y a los tres años en la AC-AL fue menor que en la AC-ATTR (46,7 y 20,0% vs. 73,4 y 35,2%, respectivamente; p=0,021). (AU)

Introduction and objetives: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease.Material and methodsOne hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations.ResultsDuring a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2).AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). (AU)

Diferencias clínicas entre la amiloidosis cardiaca por transtirretina y la cardiopatía hipertensiva / Clinical differences between transthyretin cardiac amyloidosis and hypertensive heart disease

Introducción: Un porcentaje importante de pacientes finalmente diagnosticados de amiloidosis cardIaca por transtirretina (ATTR) fueron previamente diagnosticados de cardiopatía hipertensiva (CHTA), ya que ambas enfermedades suelen cursar con insuficiencia cardíaca (IC) con fracción de eyección preservada (ICFEp) e hipertrofia ventricular. Nuestros objetivos fueron evaluar las diferencias clínicas, electrocardiográficas y ecocardiográficas, y analizar si existe un pronóstico diferencial entre ambas entidades nosológicas. Material y métodos: Se incluyeron retrospectivamente todos los pacientes con CHTA a los que se solicitó una gammagrafía cardíaca con 99mTc-Difosfonatos (GDPD) y estudio de cadenas ligeras en sangre y orina para despistaje de ATTR en nuestro centro, en el periodo 2016-2021. Para el análisis, se excluyeron aquellos diagnosticados de otros tipos de amiloidosis. Resultados: Se analizaron un total de 72 pacientes: 33 fueron diagnosticados de ATTR y 39 de CHTA, finalmente. Los pacientes con ATTR presentaron mayores niveles de troponina I ultrasensible (TnI-US) y propéptido natriurético cerebral N-terminal (NT-ProBNP); en electrocardiograma (ECG) presentaron más frecuentemente patrón de seudoinfarto y alteraciones de la conducción; en ecocardiograma transtorácico (ETT) presentaron mayor grado de hipertrofia ventricular, disfunción ventricular izquierda y parámetros de peor función diastólica, con presiones de llenado más elevadas. En el seguimiento a 4 años, el grupo de ATTR mostró mayor necesidad de marcapasos (MCP), sin evidenciarse evidencias en cuanto a mortalidad, desarrollo de fibrilación auricular o más ingresos por IC. Conclusiones: En nuestra serie, los pacientes con ATTR presentaron diferencias clínicas, electrocardiográficas y ecocardiográficas respecto a aquellos con CHTA, con mayor riesgo necesidad de MCP en el seguimiento.(AU)

Introduction: A significant percentage of patients eventually diagnosed with cardiac transthyretin amyloidosis (TTRA) was previously diagnosed with hypertensive heart disease (HHD), since both conditions usually present with heart failure (HF) with preserved ejection fraction (HFpEF) and ventricular hypertrophy. Our objectives were to evaluate the clinical, electrocardiographic and echocardiographic differences, and to analyse whether there exists a differential prognosis between these two nosological entities. Materials and methods: We retrospectively included all patients with HHD for whom a cardiac scintigraphy with 99mTc-diphosphonate (GDPD) and a free light chains test in blood and urine were ordered for ATTR screening in our centre, in the period between 2016 and 2021. Those diagnosed with other types of amyloidosis were excluded from the analysis. Results: A total of 72 patients were analyzed: 33 were finally diagnosed with TTRA and 39 with CHTA. Patients with TTRA had higher levels of ultrasensitive troponin I (TnI-US) and N-terminal brain natriuretic propeptide (NT-ProBNP); in electrocardiography (ECG) they presented a pseudo-infarction pattern more frequently as well as conduction disturbances; in echocardiography (TTE) they presented a higher degree of ventricular hypertrophy, left ventricular dysfunction and worse diastolic function parameters, with elevated filling pressures. In the 4-year follow-up, the ATTR group showed greater need for pacemaker (PCM), with no evidence regarding mortality, development of atrial fibrillation (AF), or more admissions for heart failure (HF). Conclusions: In our series, patients with TTRA showed clinical, electrocardiographic and echocardiographic differences compared to patients with HHD, with increased risk of need for PCM.(AU)

[Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis]. / Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL).

INTRODUCTION AND OBJETIVES: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease. MATERIAL AND METHODS: One hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations. RESULTS: During a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2). AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). CONCLUSIONS: CA was associated with high incidence of hospitalizations, being heart failure the most frequent individual cause; unscheduled admission-free survival in AL-CA was lower than in ATTR-CA due mostly to non-cardiovascular admissions.

«Banderas rojas» de amiloidosis cardiaca en pacientes con estenosis de canal lumbar e hipertrofia de ligamento amarillo / Red flags of cardiac amyloidosis in patients with spinal stenosis and yellow ligament hypertrophy

Introducción Carecemos de estudios que evalúen la presencia de amiloidosis cardiaca (AC) en pacientes con estenosis de canal lumbar (ECL). La identificación de banderas rojas (BR) asociadas a la enfermedad podría identificar casos de AC. Nuestro objetivo principal fue determinar la prevalencia de BR de AC. Métodos Estudio transversal de casos consecutivos que presentaban ECL e hipertrofia del ligamento amarillo (HLA). Se realizó una valoración que incluía electrocardiograma, ecocardiograma y análisis de sangre y orina. Se definió como sospecha de AC la presencia de hipertrofia ventricular y alguna BR. Resultados Se evaluaron 103 pacientes con ECL y HLA. La prevalencia de BR de AC fue elevada: insuficiencia cardiaca, 18,4%; estenosis aórtica, 1,9%; síndrome del túnel carpiano, 7,8%; rotura tendinosa bicipital, 1,9%; hipotensión arterial, 17,4%; clínica de neuropatía, 51,5%; patrón de pseudoinfarto, 3,9%; bajos voltajes, 15,5%; trastorno de la conducción, 15,5%; disminución del strain longitudinal, 25,3%; preservación apical del strain, 3,9%. El 57,3% de los pacientes presentaron sospecha de AC. Conclusión La prevalencia de BR de AC en pacientes con ECL es alta. Un elevado número de pacientes presentaron criterios de sospecha de AC. (AU)

Introduction Studies addressing the prevalence of cardiac amyloidosis (CA) among patients with spinal stenosis (SS) are lacking. The identification of the red flags (RF) of CA could lead to early detection of cases of CA. The primary objective of this study was to address the prevalence of RF of CA among patients with SS. Methods Transversal study including consecutive cases with SS and yellow ligament hypertrophy (YLH). A clinical assessment that included electrocardiogram, echocardiogram and urine and blood test was performed. A clinical suspicion of CA was defined by the presence of left ventricular hypertrophy plus any RF. Results One hundred and three patients with SS and YLH were assessed. The prevalence of RF was high: heart failure: 18.4%; aortic stenosis: 1.9%; carpal tunnel syndrome: 7.8%; bicipital tendon rupture: 1.9%; arterial hypotension: 17.4%; polyneuropathy symptoms: 51.5%; pseudoinfarction pattern: 3.9%; low voltages: 15.5%; conduction abnormalities: 15.5%; decreased longitudinal strain: 25.3%; apical sparing pattern: 3.9%. The 57.3% of the cohort met the CA suspicion criteria. Conclusion The prevalence of RF of CA is high among patients with SS and YLH. A high proportion of patients met the CA suspicion criteria. (AU)

«Banderas rojas» de amiloidosis cardiaca en pacientes con estenosis de canal lumbar e hipertrofia de ligamento amarillo / Red flags of cardiac amyloidosis in patients with spinal stenosis and yellow ligament hypertrophy

Introducción Carecemos de estudios que evalúen la presencia de amiloidosis cardiaca (AC) en pacientes con estenosis de canal lumbar (ECL). La identificación de banderas rojas (BR) asociadas a la enfermedad podría identificar casos de AC. Nuestro objetivo principal fue determinar la prevalencia de BR de AC. Métodos Estudio transversal de casos consecutivos que presentaban ECL e hipertrofia del ligamento amarillo (HLA). Se realizó una valoración que incluía electrocardiograma, ecocardiograma y análisis de sangre y orina. Se definió como sospecha de AC la presencia de hipertrofia ventricular y alguna BR. Resultados Se evaluaron 103 pacientes con ECL y HLA. La prevalencia de BR de AC fue elevada: insuficiencia cardiaca, 18,4%; estenosis aórtica, 1,9%; síndrome del túnel carpiano, 7,8%; rotura tendinosa bicipital, 1,9%; hipotensión arterial, 17,4%; clínica de neuropatía, 51,5%; patrón de pseudoinfarto, 3,9%; bajos voltajes, 15,5%; trastorno de la conducción, 15,5%; disminución del strain longitudinal, 25,3%; preservación apical del strain, 3,9%. El 57,3% de los pacientes presentaron sospecha de AC. Conclusión La prevalencia de BR de AC en pacientes con ECL es alta. Un elevado número de pacientes presentaron criterios de sospecha de AC. (AU)

Introduction Studies addressing the prevalence of cardiac amyloidosis (CA) among patients with spinal stenosis (SS) are lacking. The identification of the red flags (RF) of CA could lead to early detection of cases of CA. The primary objective of this study was to address the prevalence of RF of CA among patients with SS. Methods Transversal study including consecutive cases with SS and yellow ligament hypertrophy (YLH). A clinical assessment that included electrocardiogram, echocardiogram and urine and blood test was performed. A clinical suspicion of CA was defined by the presence of left ventricular hypertrophy plus any RF. Results One hundred and three patients with SS and YLH were assessed. The prevalence of RF was high: heart failure: 18.4%; aortic stenosis: 1.9%; carpal tunnel syndrome: 7.8%; bicipital tendon rupture: 1.9%; arterial hypotension: 17.4%; polyneuropathy symptoms: 51.5%; pseudoinfarction pattern: 3.9%; low voltages: 15.5%; conduction abnormalities: 15.5%; decreased longitudinal strain: 25.3%; apical sparing pattern: 3.9%. The 57.3% of the cohort met the CA suspicion criteria. Conclusion The prevalence of RF of CA is high among patients with SS and YLH. A high proportion of patients met the CA suspicion criteria. (AU)

Prognostic value of the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio in cardiac amyloidosis.

INTRODUCTION AND OBJECTIVES: The tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/SPAP) ratio is a noninvasive surrogate of right ventricular to pulmonary circulation that has prognostic implications in patients with heart failure (HF) or pulmonary hypertension. Our purpose was to evaluate the prognostic value of the TAPSE/SPAP ratio in patients with cardiac amyloidosis. METHODS: We used the database of the AMIGAL study, a prospective, observational registry of patients with cardiac amyloidosis recruited in 7 hospitals of the Autonomous Community of Galicia, Spain, from January 1, 2018 to October 31, 2022. We selected patients whose baseline TAPSE/SPAP ratio was calculated with transthoracic echocardiography. Long-term survival and survival free of HF hospitalization were assessed by means of 5 different multivariable Cox regression models. Median follow-up was 680 days. RESULTS: We studied 233 patients with cardiac amyloidosis, among whom 209 (89.7%) had transthyretin type. The baseline TAPSE/SPAP ratio correlated significantly with clinical outcomes. Depending on the multivariable model considered, the adjusted hazard ratios estimated per 0.1mm/mmHg increase of baseline TAPSE/SPAP ratio ranged from 0.76 to 0.84 for all-cause mortality. Similarly, the ratios for all-cause mortality of HF hospitalization ranged from 0.79 to 0.84. The addition of the baseline TAPSE/SPAP ratio to the predictive model of the United Kingdom National Amyloidosis Centre resulted in an increase in Harrell's c-statistic from 0.662 to 0.705 for all-cause mortality and from 0.668 to 0.707 for all-cause mortality or HF hospitalization. CONCLUSIONS: Reduced TAPSE/SPAP ratio is an independent adverse prognostic marker in patients with cardiac amyloidosis.

Clinical differences between transthyretin cardiac amyloidosis and hypertensive heart disease. / Diferencias clínicas entre la amiloidosis cardiaca por transtirretina y la cardiopatía hipertensiva.

INTRODUCTION: A significant percentage of patients eventually diagnosed with cardiac transthyretin amyloidosis (TTRA) was previously diagnosed with hypertensive heart disease (HHD), since both conditions usually present with heart failure (HF) with preserved ejection fraction (HFpEF) and ventricular hypertrophy. Our objectives were to evaluate the clinical, electrocardiographic and echocardiographic differences, and to analyse whether there exists a differential prognosis between these two nosological entities. MATERIALS AND METHODS: We retrospectively included all patients with HHD for whom a cardiac scintigraphy with 99mTc-diphosphonate (GDPD) and a free light chains test in blood and urine were ordered for ATTR screening in our centre, in the period between 2016 and 2021. Those diagnosed with other types of amyloidosis were excluded from the analysis. RESULTS: A total of 72 patients were analyzed: 33 were finally diagnosed with TTRA and 39 with CHTA. Patients with TTRA had higher levels of ultrasensitive troponin I (TnI-US) and N-terminal brain natriuretic propeptide (NT-ProBNP); in electrocardiography (ECG) they presented a pseudo-infarction pattern more frequently as well as conduction disturbances; in echocardiography (TTE) they presented a higher degree of ventricular hypertrophy, left ventricular dysfunction and worse diastolic function parameters, with elevated filling pressures. In the 4-year follow-up, the ATTR group showed greater need for pacemaker (PCM), with no evidence regarding mortality, development of atrial fibrillation (AF), or more admissions for heart failure (HF). CONCLUSIONS: In our series, patients with TTRA showed clinical, electrocardiographic and echocardiographic differences compared to patients with HHD, with increased risk of need for PCM.

[Red flags of cardiac amyloidosis in patients with spinal stenosis and yellow ligament hypertrophy]. / «Banderas rojas¼ de amiloidosis cardiaca en pacientes con estenosis de canal lumbar e hipertrofia de ligamento amarillo.

INTRODUCTION: Studies addressing the prevalence of cardiac amyloidosis (CA) among patients with spinal stenosis (SS) are lacking. The identification of the red flags (RF) of CA could lead to early detection of cases of CA. The primary objective of this study was to address the prevalence of RF of CA among patients with SS. METHODS: Transversal study including consecutive cases with SS and yellow ligament hypertrophy (YLH). A clinical assessment that included electrocardiogram, echocardiogram and urine and blood test was performed. A clinical suspicion of CA was defined by the presence of left ventricular hypertrophy plus any RF. RESULTS: One hundred and three patients with SS and YLH were assessed. The prevalence of RF was high: heart failure: 18.4%; aortic stenosis: 1.9%; carpal tunnel syndrome: 7.8%; bicipital tendon rupture: 1.9%; arterial hypotension: 17.4%; polyneuropathy symptoms: 51.5%; pseudoinfarction pattern: 3.9%; low voltages: 15.5%; conduction abnormalities: 15.5%; decreased longitudinal strain: 25.3%; apical sparing pattern: 3.9%. The 57.3% of the cohort met the CA suspicion criteria. CONCLUSION: The prevalence of RF of CA is high among patients with SS and YLH. A high proportion of patients met the CA suspicion criteria.

Monitoring cardiac amyloidosis with multimodality imaging.

Cardiac amyloidosis (CA) refers to an infiltrative process involving amyloid fibril deposition in the myocardium causing restrictive cardiomyopathy. While various types can affect the heart, the predominant forms are immunoglobulin light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis. This review article explores the expanding field of imaging techniques used to diagnose AL-CA and ATTR-CA, highlighting their usefulness in prognostication and disease surveillance. Echocardiography is often the initial imaging modality to suspect CA and, since the incorporation of nonbiopsy criteria using bone scintigraphy, diagnosing ATTR-CA has become more attainable following exclusion of plasma cell dyscrasia. Cardiac magnetic resonance is progressively emerging as a vital tool for imaging CA, and is used in diagnosis, prognostication, and disease surveillance. The use of cardiac magnetic resonance in AL-CA is discussed, as it has been shown to accurately evaluate organ response to chemotherapy. As novel drug treatments emerge in the realm of ATTR-CA, the use of cardiovascular imaging surveillance to monitor disease progression is discussed, as it is gaining prominence as a critical consideration. The ongoing phase III trials investigating treatments for patients with ATTR-CA, will undoubtedly enhance our understanding of cardiac imaging surveillance.

Impact of SARS-CoV-2 infection in patients with cardiac amyloidosis: Results of a multicentre registry / Impacto de la infección por SARS-CoV-2 en pacientes con amiloidosis cardiaca: resultados de un registro multicéntrico

Background Descriptions on impact of SARS-CoV-2 infection in patients with cardiac amyloidosis (CA) are lacking. Our aim was to describe the prognosis of those patients. Methods Retrospective observational study of unvaccinated patients with CA who developed SARS-CoV-2 infection enrolled in eleven centres (March 2020 to May 2021). Descriptive analysis of basal characteristics, hospitalization, mortality, and severe clinical course was performed. Comparisons to a population-based control group were made. Results Forty-one patients were identified. Most patients had wild-type transthyretin CA (61%) and were on NYHA Class II–III (80.5%). CA patients were commonly hospitalized (73.2%) and those were more symptomatic than outpatients (p=0.035). The 24.4% of CA patients died as consequence of SARS-CoV-2 infection. Patients with CA had an increased risk of hospitalization [OR 6.23 (3.05–12.74), p<0.001] and mortality [OR 2.18 (1.01–4.68), p=0.047] when compared to control population after adjustment by age and sex. After a medium follow-time of 311 days, 41.5% of the CA cohort died. Conclusions SARS-CoV-2 infection is associated with high mortality and hospitalization rates in patients with CA, which exceed that expected by their sex and advanced age (AU)

Antecedentes El impacto de la infección por SARS-CoV-2 en pacientes con amiloidosis cardíaca (AC) es desconocido. El principal objetivo de este estudio es describir el pronóstico de estos pacientes. Métodos Estudio observacional retrospectivo de pacientes con AC no vacunados que desarrollaron infección por SARS-CoV-2 identificados en 11 centros (marzo 2020/mayo 2021). Se realiza un análisis descriptivo de características basales, hospitalización, mortalidad y curso clínico grave, y se comparan los resultados con una cohorte poblacional. Resultados Cuarenta y un pacientes fueron identificados. La mayoría eran AC por transtirretina wild-type (61%) y estaban en clase NYHA II-III (80,5%). La mayoría de los pacientes fueron hospitalizados (73,2%), los cuales tenían peor clase funcional que los ambulatorios (p=0,035). El 24,4% de los pacientes fallecieron como consecuencia de la infección. Los pacientes con AC tenían un mayor riesgo de hospitalización (OR: 6,23; 3.05-12.74; p<0,001) y fallecimiento (OR: 2,18; 1,01-4,68; p=0,047) que la cohorte poblacional tras ajuste por sexo y edad. Tras un seguimiento medio de 311 días, el 41,5% de los pacientes fallecieron. Conclusiones La infección por SARS-CoV-2 presenta alto riesgo de mortalidad y hospitalización en pacientes con AC, mayor que la esperada por su sexo y edad (AU)

¿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)

Relevancia del estudio genético de la amiloidosis cardíaca por transtiretina en el anciano / Importance of genetic study in elderly patients with transthyretin cardiac amyloidosis

Antecedentes y objetivo La amiloidosis cardiaca por transtiretina (AC-ATTR) es una enfermedad prevalente con la edad. Se recomienda realizar sistemáticamente un estudio genético incluso en los pacientes más añosos. Nuestro objetivo ha sido realizar un análisis de la prevalencia de amiloidosis por transtiretina hereditaria (ATTRv) en ancianos (≥75años) con AC-ATTR y sus implicaciones. Pacientes y método Estudio observacional retrospectivo de la cohorte de pacientes ancianos con AC-ATTR diagnosticados de acuerdo con el protocolo internacional. Analizamos los resultados de la secuenciación del gen TTR, las características diferenciales y sus implicaciones clínicas. Resultados Entre 2016 y 2022 se diagnosticaron 130 pacientes ancianos (89% cohorte) con AC-ATTR (85% varones). En 8 pacientes de los 123 con estudio genético se identificó una variante patogénica en TTR (6,5%), iniciándose tratamiento específico en 4 sujetos (50%). El estudio familiar identificó otro caso y 6 portadores asintomáticos. No hubo diferencias significativas entre características basales ni en los eventos clínicos. Conclusiones La prevalencia de ATTRv en ancianos con AC-ATTR fue del 6,5%, sin observarse características diferenciales que permitan guiar una indicación selectiva del análisis genético (AU)

Background and objective Cardiac transthyretin amyloidosis (CA-ATTR) is a prevalent disease with age. Genetic study is recommended, even in eldest patients. We aim to analyze the prevalence of hereditary transthyretin amyloidosis (ATTRv) in elderly patients (≥75years) with CA-ATTR and its implications. Patients and methodology Retrospective observational study of the cohort of elderly patients with CA-ATTR diagnosed according to the international recommended protocol. We analyze the results of sequencing TTR gene, the differential characteristics and their clinical implications. Results Between 2016 and 2022, 130 elderly patients (89% cohort) were diagnosed with CA-ATTR (85% male). In 8 of the 123 patients with a genetic study, a pathogenic variant in TTR was identified (6.5%), initiating specific treatment in 4 subjects (50%). The family study identified another case and 6 asymptomatic carriers. There were no significant differences between baseline characteristics or in clinical events. Conclusions The prevalence of ATTRv in elderly patients with CA-ATTR was 6.5% without observing differential characteristics that allow guiding a selective indication of genetic analysis (AU)

Impact of SARS-CoV-2 infection in patients with cardiac amyloidosis: Results of a multicentre registry.

BACKGROUND: Descriptions on impact of SARS-CoV-2 infection in patients with cardiac amyloidosis (CA) are lacking. Our aim was to describe the prognosis of those patients. METHODS: Retrospective observational study of unvaccinated patients with CA who developed SARS-CoV-2 infection enrolled in eleven centres (March 2020 to May 2021). Descriptive analysis of basal characteristics, hospitalization, mortality, and severe clinical course was performed. Comparisons to a population-based control group were made. RESULTS: Forty-one patients were identified. Most patients had wild-type transthyretin CA (61%) and were on NYHA Class II-III (80.5%). CA patients were commonly hospitalized (73.2%) and those were more symptomatic than outpatients (p=0.035). The 24.4% of CA patients died as consequence of SARS-CoV-2 infection. Patients with CA had an increased risk of hospitalization [OR 6.23 (3.05-12.74), p<0.001] and mortality [OR 2.18 (1.01-4.68), p=0.047] when compared to control population after adjustment by age and sex. After a medium follow-time of 311 days, 41.5% of the CA cohort died. CONCLUSIONS: SARS-CoV-2 infection is associated with high mortality and hospitalization rates in patients with CA, which exceed that expected by their sex and advanced age.

Importance of genetic study in elderly patients with transthyretin cardiac amyloidosis. / Relevancia del estudio genético de la amiloidosis cardíaca por transtiretina en el anciano.

BACKGROUND AND OBJECTIVE: Cardiac transthyretin amyloidosis (CA-ATTR) is a prevalent disease with age. Genetic study is recommended, even in eldest patients. We aim to analyze the prevalence of hereditary transthyretin amyloidosis (ATTRv) in elderly patients (≥75years) with CA-ATTR and its implications. PATIENTS AND METHODOLOGY: Retrospective observational study of the cohort of elderly patients with CA-ATTR diagnosed according to the international recommended protocol. We analyze the results of sequencing TTR gene, the differential characteristics and their clinical implications. RESULTS: Between 2016 and 2022, 130 elderly patients (89% cohort) were diagnosed with CA-ATTR (85% male). In 8 of the 123 patients with a genetic study, a pathogenic variant in TTR was identified (6.5%), initiating specific treatment in 4 subjects (50%). The family study identified another case and 6 asymptomatic carriers. There were no significant differences between baseline characteristics or in clinical events. CONCLUSIONS: The prevalence of ATTRv in elderly patients with CA-ATTR was 6.5% without observing differential characteristics that allow guiding a selective indication of genetic analysis.

Amiloidosis cardiaca y cierre de aurícula izquierda. Estudio CAMYLAAC / Cardiac amyloidosis and left atrial appendage closure. The CAMYLAAC study

Introducción y objetivos: La amiloidosis cardiaca por transtirretina (ACTTR) se asocia con fibrilación auricular y un riesgo trombótico y hemorrágico aumentados. Nuestro objetivo fue evaluar los resultados del cierre percutáneo de orejuela izquierda (COI) comparado con pacientes sin diagnóstico conocido de ACTTR. Métodos: Comparación de la evolución a largo plazo de pacientes con diagnóstico de ACTTR frente a pacientes sin ese diagnóstico sometidos a COI entre 2009 y 2021. Resultados: Se incluyó a 1.159 pacientes de los que 40 (3,5%) fueron diagnosticados de ACTTR; fueron más ancianos, con más comorbilidades, mayores puntuaciones HAS-BLED y CHA2DS2-VASc y menor función ventricular izquierda. Se consiguió el COI exitoso en 1.137 pacientes (98,1%) sin diferencias entre los grupos. No hubo diferencias intrahospitalarias ni al seguimiento en ictus isquémico (5 frente a 2,5%, p=0,283), ictus hemorrágico (2,5 frente a 0,8%, p=0,284), ni sangrado mayor o menor. La mortalidad a 2 años no presentaba diferencias entre los pacientes con ACTTR y los que no presentaban este diagnóstico (20 frente a 13,6%, 0,248); sin embargo, a los 5 años los pacientes ACTTR presentaron mayor mortalidad (40 frente a 19,2%, p <0,001) pero no relacionada con complicaciones hemorrágicas o ictus isquémico. Conclusiones: El COI podría reducir complicaciones hemorrágicas y accidentes cerebrovasculares sin incrementar las complicaciones precoces en pacientes con ACTTR. Aunque la supervivencia a largo plazo en pacientes con ACTTR es muy reducida, a dos años fue comparable a la del grupo sin diagnóstico de ACTTR lo que sugiere que el COI no es fútil en pacientes con ACTTR. (AU)

Introduction and objectives: Transthyretin cardiac amyloidosis (ATTR-CA) patients often have atrial fibrillation and increased bleeding/thrombogenic risks. We aimed to evaluate outcomes of left atrial appendage closure (LAAC) compared with patients without a known diagnosis of CA. Methods: Comparison at long-term of patients diagnosed with ATTR-CA who underwent LAAC between 2009 and 2020 and those without a known diagnosis of CA. Results: We studied a total of 1159 patients. Forty patients (3.5%) were diagnosed with ATTR-CA; these patients were older and had more comorbidities, higher HAS-BLED and CHA2DS2-VASc scores, and lower left ventricular function. Successful LAAC was achieved in 1137 patients (98.1%) with no differences between groups. Regarding in-hospital and follow-up complications, there were no differences between the groups in ischemic stroke (5% vs 2.5% in those without a known diagnosis of CA; P=.283), hemorrhagic stroke (2.5% and 0.8% in the control group; P=.284), major or minor bleeding. At the 2-year follow-up, there were no significant differences in mortality (ATTR-CA: 20% vs those without known CA: 13.6%, 0.248); however, the at 5-year follow-up, ATTR-CA patients had higher mortality (40% vs 19.2%; P <.001) but this difference was unrelated to hemorrhagic complications or ischemic stroke. Conclusions: LAAC could reduce the risk of bleeding complications and ischemic cerebrovascular events without increasing the rate of early or mid-term complications. Although long-term survival was impaired in ATTR-CA patients, it was comparable to that of patients without a known diagnosis of CA at the 2-year follow-up, suggesting that LAAC for patients with ATTR-CA might not be futile. (AU)

Descripción de un método de cuantificación diferente para la carga de amiloide (DPDload) y validación de SPECT/TC en amiloidosis cardíaca / Description of a different quantification method for amyloid burden (burdenDPD) and validation of SPECT/CT in cardiac amyloidosis

Introducción Los radiotrazadores con afinidad ósea como el [99mTc]Tc-DPD han demostrado una alta sensibilidad y especificidad en el diagnóstico no invasivo de la amiloidosis cardíaca (AC) por transtirretina (ATTR-AC). Este estudio tiene como objetivo validar el uso de la SPECT/TC y evaluar la utilidad de la cuantificación de la captación (cargaDPD) en el tejido miocárdico como información potencial sobre la carga amiloide. Métodos Se trata de un análisis retrospectivo de 46 pacientes con sospecha de AC, en el que 23 casos con ATTR-AC fueron sometidos a dos métodos de cuantificación para estimar la carga amiloide (cargaDPD) a través de imágenes planares y de una SPECT/TC. Resultados La SPECT/TC aportó un valor añadido significativo en el diagnóstico del paciente con AC (p<0,05). La estimación de la carga amiloide comprobó que la pared del VI más afectada es el tabique interventricular en la mayoría de los casos, y la existencia de una relación significativa entre la captación de Perugini y la carga de DPD. Conclusiones Validamos la necesidad de la SPECT/TC como complemento de la imagen planar en el diagnóstico de la AC-TTR. Por su parte, el cálculo de la carga amiloide continúa siendo un área de investigación compleja y requiere de más estudios, con un mayor número de pacientes, que permitan validar un método estandarizado de cuantificación de la carga de amiloide, tanto para el diagnóstico como para el seguimiento del tratamiento (AU)

Background Bone tracers such as [99mTc]Tc-DPD have shown high sensitivity and specificity in the non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-AC). This study aims to validate SPECT/CT and assess the usefulness of uptake quantification (burdenDPD) in the myocardial tissue as potential information on the amyloid burden. Methods In a retrospective analysis of 46 patients with suspected CA, 23 cases with ATTR-AC had two quantification methods conducted to estimate amyloid burden (burdenDPD) through planar scintigraphic scans and a SPECT/CT. Results SPECT/CT significantly provided an added value in the patient's diagnosis with CA (P<.05). The estimation of the amyloid burden substantiated that the most affected wall of the LV is the interventricular septum in most cases and the existence of a significant relationship between the Perugini score uptake and the burdenDPD. Conclusions We validate the need for SPECT/CT to complement planar imaging in diagnosing ATTR-AC. For its part, quantifying the amyloid load continues to be a complex area of research. It requires further studies with a larger number of patients to validate a standardized method of amyloid load quantification, both for diagnosis and treatment monitoring (AU)

Description of a different quantification method for amyloid burden (DPDload) and validation of SPECT/CT in cardiac amyloidosis.

BACKGROUND: Bone tracers such as 99mTc-DPD have shown high sensitivity and specificity in the non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). This study aims to validate SPECT/CT and assess the usefulness of uptake quantification (DPDload) in the myocardial tissue as potential information on the amyloid burden. METHODS: In a retrospective analysis of 46 patients with suspected CA, 23 cases with ATTR-CA had two quantification methods conducted to estimate amyloid burden (DPDload) through planar scintigraphic scans and a SPECT/CT. RESULTS: SPECT/CT significantly provided an added value in the patient's diagnosis with CA (P<.05). The estimation of the amyloid burden substantiated that the most affected wall of the LV is the interventricular septum in most cases and the existence of a significant relationship between the Perugini score uptake and the DPDload. CONCLUSIONS: We validate the need for SPECT/CT to complement planar imaging in diagnosing ATTR-CA. For its part, quantifying the amyloid load continues to be a complex area of research. It requires further studies with a larger number of patients to validate a standardized method of amyloid load quantification, both for diagnosis and treatment monitoring.

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.

Prevalence of transthyretin cardiac amyloidosis in elderly patients diagnosed with heart failure / Prevalencia de amiloidosis cardiaca por transtirretina en pacientes de edad avanzada con diagnóstico de insuficiencia cardiaca

Objective: There is increased interest in studying ATTR-CA, a pathology that primarily affects patients of geriatric age and is frequently underdiagnosed. We aim to establish the prevalence of ATTR-CA in a cohort of patients with a history of HFpEF and to describe its characteristics. Methods: We conducted a prospective observational study. Patients ≥75 years, clinical history of HFpEF, atrial dilation ≥34ml/m2 and left ventricular wall thickening >13mm, were included. Demographic and analytical parameters were collected, and a comprehensive geriatric assessment was performed, along with a transthoracic echocardiogram and cardiac scintigraphy. Finally, telephone follow-up was carried out at 6 and 12 months. Results: 50 patients were recruited, mean age 86±6 years, 54% women. Age and functional class (I–II vs. III–IV) were factors associated with presenting with ATTR-CA. Patients with positive scintigraphy had a median time to admission of 5.2 months (confidence interval [CI] 95% 0–10.9), while in those with negative scintigraphy, it was 12.2 months (95% CI 11.7–12.8); log-rank: p=0.064. Patients with positive scintigraphy had a median time to the combined endpoint (death and readmission) of 1.9 months (95% CI 0–6.1), and patients with negative scintigraphy of 11.9 months (95% CI 11.7–12); log-rank: p=0.027. Conclusions: ATTR-CA appears to be a prevalent etiology in elderly patients within the spectrum of HFpEF. Patients with a diagnosis of ATTR-CA had a shorter time to admission for HF and the combined event of death and admission than patients with a negative result on scintigraphy. (AU)

Objetivo: Existe un interés creciente por el estudio de AC-TTR, siendo esta una patología que afecta fundamentalmente a pacientes de edad avanzada y que es frecuentemente infradiagnosticada. Nuestro objetivo fue establecer la prevalencia de AC-TTR en una cohorte de pacientes con historia de ICFEp y describir sus características. Métodos: Estudio observacional prospectivo. Se incluyeron pacientes ≥75 años, con historia clínica de ICFEp, dilatación auricular ≥34ml/m2 y engrosamiento de la pared del ventrículo izquierdo >13mm. Se recogieron datos analíticos y demográficos, así como de la valoración geriátrica integral y se realizó un ecocardiograma transtorácico y una gammagrafía cardiaca. Finalmente se realizó seguimiento telefónico a los 6 y 12 meses. Resultados: Se incluyó a 50 pacientes, edad media 86±6 años, 54% mujeres. La edad y la clase funcional NYHA (I-II vs. III-IV) se asociaron con mayor riesgo de presentar AC-TTR. Los pacientes con gammagrafía positiva tuvieron una mediana de tiempo al ingreso de 5,2 meses (intervalo de confianza [IC] 95% 0-10,9), frente a aquellos con gammagrafía negativa que fue de 12,2 meses (IC 95% 11,7-12,8); log-rank: p=0,064. Los pacientes con gammagrafía positiva presentaron una mediana de tiempo al evento combinado (muerte y reingreso) de 1,9 meses (IC 95% 0-6,1), mientras que en aquellos con resultado negativo fue de 11,9 meses (IC 95% 11,7-12); log-rank: p=0.027. Conclusiones: La AC-TTR supone una etiología prevalente de insuficiencia cardiaca, dentro del espectro de la ICFEp, en pacientes de edad avanzada. Los individuos con diagnóstico de AC-TTR presentaron un menor tiempo al ingreso por insuficiencia cardiaca y al evento combinado de muerte y reingreso frente a aquellos pacientes con resultado negativo en la gammagrafía. (AU)