ABSTRACT
AIM: To estimate the prevalence of amyloid cardiomyopathy (CM) caused by transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) amyloidosis among patients aged >65 years with interventricular septal (IVS) hypertrophy of ≥14âmm. MATERIAL AND METHODS: From January through August 2023, 60 patients (mean age 7.2±7.3 years, 34 (56.67%) men) were enrolled. Patients meeting the inclusion criteria underwent an echocardiographic study with determining the myocardial longitudinal strain, myocardial scintigraphy with 99mTc-pyrfotech, myocardial single-photon emission computed tomography, measurement of N-terminal fragment of brain natriuretic peptide and troponin I, and the immunochemical study of serum and urine proteins with measurement of free light chains. In the presence of grades 2 and 3 radiopharmaceutical uptake according to scintigraphy, a molecular genetic study was performed for differential diagnosis of wild-type transthyretin amyloidosis (wtATTR) and hereditary/variant (hATTR) ATTR-CM. RESULTS: According to data of myocardial scintigraphy with 99mTc-pyrfotech, grade 3 uptake in the absence of monoclonal secretion was detected in 5 (8.3%) cases and grade 2 radiotracer uptake in the absence of monoclonal secretion was detected in 6 (10%) patients. Myeloma complicated by AL amyloidosis and primary AL amyloidosis were found in 5 (8.3%) patients. CONCLUSION: Among patients aged ≥65 years with IVS hypertrophy ≥14âmm, amyloid CM was detected in 20% of cases (12 patients), including 5 cases (8.3%) of AL amyloidosis and 7 cases (11.7%) of ATTR amyloidosis.
Subject(s)
Amyloid Neuropathies, Familial , Echocardiography , Hypertrophy, Left Ventricular , Humans , Male , Female , Russia/epidemiology , Aged , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/diagnosis , Prevalence , Hypertrophy, Left Ventricular/epidemiology , Echocardiography/methods , Immunoglobulin Light-chain Amyloidosis/epidemiology , Immunoglobulin Light-chain Amyloidosis/complications , Tomography, Emission-Computed, Single-Photon/methods , Cardiomyopathies/epidemiologyABSTRACT
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)
Subject(s)
Humans , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/therapy , Cardiomyopathies/epidemiology , Cardiomyopathies/etiology , Cardiomyopathies/therapy , Heart Failure/complications , Heart Failure/epidemiology , Heart Failure/therapy , Hospitalization , PrealbuminSubject(s)
Amyloid Neuropathies, Familial , Heart Failure , Stroke Volume , Humans , Heart Failure/physiopathology , Heart Failure/epidemiology , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/physiopathology , Amyloid Neuropathies, Familial/complications , Stroke Volume/physiology , Male , Female , Prevalence , Prospective Studies , Aged , Middle Aged , Prealbumin/geneticsABSTRACT
BACKGROUND: Aortic stenosis (AS) is currently the most common valvular disease, with an estimated prevalence of over 4% in octogenarians. OBJECTIVE: To describe the prevalence of moderate-severe aortic stenosis (AS) in patients with wild type transthyretin amyloidosis (ATTRwt). Also, describe the clinical features, echocardiographic characteristics and clinical evolution. METHOD: Retrospective cohort of patients with diagnosis of ATTRwt, belonging to Hospital Italiano de Buenos Aires Institutional Amyloidosis Registry, from 30/11/2007 to 31/05/2021. Patients follow up was carried out through the institution clinical history. The prevalence of moderate-severe AE was estimated and presented as a percentage with its 95% confidence interval (95% CI). The characteristics were compared by groups according to whether or not they had moderate-severe AS. RESULTS: 104 patients with ATTRwt were included. Median follow up was 476 days [interquartile range: 192-749]. Moderate-severe AS prevalence at the ATTRwt time of diagnosis was 10.5% (n = 11; 95% CI: 5-18%). The median age of patients with AS moderate-severe at the time of diagnosis of ATTRwt was 86 years [78-91] and the male sex predominated (82%). Most of the patients had a history of heart failure (n = 8) and atrial fibrillation (n = 8) prior to the diagnosis of ATTRwt. Most of the patients were subclassified as low flow low gradient severe AS group (n = 7). Four patients underwent some intervention on the aortic valve. During follow-up, 5 patients (46%) were hospitalized for decompensated heart failure and 4 (36%) died. CONCLUSIONS: In our cohort, the coexistence of both pathologies had a similar prevalence as reported in the international literature. It was an elderly population with a high percentage of atrial fibrillation and history of heart failure. Most of the patients presented with severe AS with low flow low gradient.
ANTECEDENTES: La estenosis aórtica (EA) es actualmente la enfermedad valvular más frecuente, con una prevalencia estimada de más del 4 % en octogenarios. OBJETIVO: Describir la prevalencia de estenosis aórtica (EA) moderada-grave en pacientes con amiloidosis por transtiretina wild type (ATTRwt). Además, describir las características clínicas, ecocardiográficas y la evolución en este grupo de pacientes. MÉTODO: Estudio de cohorte retrospectiva de pacientes con diagnóstico de ATTRwt, pertenecientes al Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, en el periodo del 30/11/2007 al 31/05/2021. El seguimiento de los pacientes se realizó a través de la historia clínica electrónica de la institución. Se estimó la prevalencia de EA moderada-grave, que se presenta como porcentaje con su intervalo de confianza del 95% (IC 95%). Se compararon las características por grupos según tuvieran o no EA moderada-grave. RESULTADOS: Se incluyeron 104 pacientes con diagnóstico de ATTRwt. La mediana de seguimiento fue de 476 días [rango intercuartílico: 192-749]. La prevalencia de EA moderada-grave al momento del diagnóstico de ATTRwt fue del 10.5% (n = 11; IC95%: 5-18%). La mediana de edad de los pacientes con EA fue de 86 años [78-91] y predominó el sexo masculino (81.8%). La mayoría de los pacientes tenían el antecedente de insuficiencia cardiaca (n = 8) y fibrilación auricular (n = 8). Predominaron los pacientes con EA grave de bajo flujo y bajo gradiente (n = 7). Cuatro pacientes fueron sometidos a alguna intervención en la válvula aórtica. Durante el seguimiento, 5 pacientes (46%) tuvieron internaciones por insuficiencia cardiaca descompensada y 4 (36%) fallecieron. CONCLUSIONES: En nuestra cohorte, la coexistencia de ambas patologías tuvo una prevalencia similar a la reportada en la literatura internacional. Se trató de una población añosa con alto porcentaje de fibrilación auricular y antecedente de insuficiencia cardiaca. La mayoría presentaron EA grave de bajo flujo y bajo gradiente.
Subject(s)
Amyloid Neuropathies, Familial , Aortic Valve Stenosis , Atrial Fibrillation , Heart Failure , Aged, 80 and over , Humans , Male , Aged , Retrospective Studies , Atrial Fibrillation/complications , Prevalence , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/epidemiology , Heart Failure/etiology , Heart Failure/complications , Aortic Valve Stenosis/complications , Aortic Valve Stenosis/epidemiologyABSTRACT
OBJECTIVES: To identify and describe the profile of potential transthyretin cardiac amyloidosis (ATTR-CM) cases in the Brazilian public health system (SUS), using a predictive machine learning (ML) model. METHODS: This was a retrospective descriptive database study that aimed to estimate the frequency of potential ATTR-CM cases in the Brazilian public health system using a supervised ML model, from January 2015 to December 2021. To build the model, a list of ICD-10 codes and procedures potentially related with ATTR-CM was created based on literature review and validated by experts. RESULTS: From 2015 to 2021, the ML model classified 262 hereditary ATTR-CM (hATTR-CM) and 1,581 wild-type ATTR-CM (wtATTR-CM) potential cases. Overall, the median age of hATTR-CM and wtATTR-CM patients was 66.8 and 59.9 years, respectively. The ICD-10 codes most presented as hATTR-CM and wtATTR-CM were related to heart failure and arrythmias. Regarding the therapeutic itinerary, 13% and 5% of hATTR-CM and wtATTR-CM received treatment with tafamidis meglumine, respectively, while 0% and 29% of hATTR-CM and wtATTR-CM were referred to heart transplant. CONCLUSION: Our findings may be useful to support the development of health guidelines and policies to improve diagnosis, treatment, and to cover unmet medical needs of patients with ATTR-CM in Brazil.
Subject(s)
Amyloid Neuropathies, Familial , Amyloidosis , Cardiomyopathies , Humans , Brazil/epidemiology , Prealbumin , Public Health , Retrospective Studies , Machine Learning , Cardiomyopathies/diagnosis , Cardiomyopathies/epidemiology , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/epidemiologyABSTRACT
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.
Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Heart Failure , Immunoglobulin Light-chain Amyloidosis , Humans , Incidence , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/therapy , Prealbumin , Immunoglobulin Light-chain Amyloidosis/complications , Heart Failure/epidemiology , Heart Failure/therapy , Heart Failure/complications , Hospitalization , Cardiomyopathies/epidemiology , Cardiomyopathies/etiology , Cardiomyopathies/therapyABSTRACT
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.
Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Heart Failure , Adult , Humans , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/epidemiology , Cardiomyopathies/diagnosis , Cardiomyopathies/epidemiology , Cardiomyopathies/complications , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Failure/complications , Prealbumin , Prevalence , Prospective StudiesABSTRACT
BACKGROUND: Even if prevalent among patients with severe aortic stenosis (AS), the clinical suspicion for transthyretin cardiac amyloidosis (ATTR-CA) remains difficult in this subset. We report our single center experience on ATTR-CA detection among TAVR candidates to provide insights on the prevalence and clinical features of dual pathology as compared to lone AS. METHODS: Consecutive severe AS patients undergoing transcatheter aortic valve replacement (TAVR) evaluation at a single center were prospectively included. Those with suspected ATTR-CA based on clinical assessment underwent 99m Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy. The RAISE score, a novel screening tool with high sensitivity for ATTR-CA in AS, was retrospectively calculated to rule-out ATTR-CA in the remaining patients. Patients were categorized as follow: "ATTR-CA+": patients with confirmed ATTR-CA at DPD bone scintigraphy; "ATTR-CA-": patients with negative DPD bone scintigraphy or a negative RAISE score; "ATTR-CA indeterminate": patients not undergoing ATTR-CA assessment with a positive RAISE score. The characteristics of ATTR-CA+ and ATTR-CA- patients were compared. RESULTS: Of 107 included patients, ATTR-CA suspicion was posed in 13 patients and confirmed in six. Patients were categorized as follow: 6 (5.6%) ATTR-CA+, 79 (73.8%) ATTR-CA-, 22 (20.6%) ATTR-CA indeterminate. Excluding ATTR-CA indeterminate patients, the prevalence of ATTR-CA was 7.1% (95% CI 2.6-14.7%). As compared to ATTR-CA - patients, ATTR-CA + patients were older, had higher procedural risk and more extensive myocardial and renal damage. They had higher left ventricle mass index and lower ECG voltages, translating into a lower voltage to mass ratio. Moreover, we describe for the first time bifascicular block as an ECG feature highly specific of patients with dual pathology (50.0% vs. 2.7%, P<0.001). Of note, pericardial effusion was rarely found in patients with lone AS (16.7% vs. 1.2%, P=0.027). No difference in procedural outcomes was observed between groups. CONCLUSIONS: Among severe AS patients, ATTR-CA is prevalent and presents with phenotypic features that may aid to differentiate it from lone AS. A clinical approach based on routine search of amyloidosis features might lead to selective DPD bone scintigraphy with a satisfactory positive predictive value.
Subject(s)
Amyloid Neuropathies, Familial , Aortic Valve Stenosis , Cardiomyopathies , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Prealbumin , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/epidemiology , Cardiomyopathies/surgery , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/surgery , Retrospective Studies , Tomography, X-Ray Computed , Aortic Valve Stenosis/epidemiology , Aortic Valve Stenosis/surgeryABSTRACT
BACKGROUND: Precise data about ATTR-CM incidence rates at national level are scarce. Consequently, this study aimed to estimate the annual incidence and survival of transthyretin amyloid cardiomyopathy (ATTR-CM) in France between 2011 and 2019 using real world data. We used the French nationwide exhaustive data (SNDS database) gathering in- and out-patient claims. As there is no specific ICD-10 marker code for ATTR-CM, diagnosis required both amyloidosis (identified by E85. ICD-10 code or a tafamidis meglumine delivery) and a cardiovascular condition (identified by ICD-10 or medical procedure codes related to either heart failure, arrhythmias, conduction disorders or cardiomyopathies), not necessarily reported at the same visit. Patients with probable AL-form of amyloidosis or probable AA-form of amyloidosis were excluded. RESULTS: Between 2011 and 2019, 8,950 patients with incident ATTR-CM were identified. Incidence rates increased from 0.6 / 100,000 person-years in 2011 to 3.6 / 100,000 person-years in 2019 (p < 0.001), reaching 2377 new cases in 2019. Sex ratios (M/F) increased from 1.52 in 2011 to 2.23 in 2019. In 2019, median age at diagnosis was 84.0 years (85.5 for women and 83.5 for men). Median survival after diagnosis was 41.9 months (95% CI [39.6, 44.1]). CONCLUSIONS: This is the first estimate of nationwide ATTR-CM incidence in France using comprehensive real-world databases. We observed an increased incidence over the study period, consistent with an improvement in ATTR-CM diagnosis in recent years.
Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Female , Humans , Male , Amyloid Neuropathies, Familial/epidemiology , Cardiomyopathies/drug therapy , Cardiomyopathies/epidemiology , Cardiomyopathies/diagnosis , Incidence , Outpatients , Prealbumin , Aged , FranceABSTRACT
AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM), a progressive and fatal cardiomyopathy, is frequently misdiagnosed or entails diagnostic delays, hindering patients from timely treatment. This study aimed to generate a systematic framework based on data from electronic health records (EHRs) to assess patients with ATTR-CM in a real-world population of heart failure (HF) patients. Predictive factors or combinations of predictive factors related to ATTR-CM in a European population were also assessed. METHODS AND RESULTS: Retrospective unstructured and semi-structured data from EHRs of patients from OLV Hospital Aalst, Belgium (2012-20), were processed using natural language processing (NLP) to generate an Observational Medical Outcomes Partnership Common Data Model database. NLP model performance was assessed on a random subset of EHRs by comparing algorithm outputs to a physician-generated standard (using precision, recall, and their harmonic mean, or F1-score). Of the 3127 HF patients, 103 potentially had ATTR-CM (age 78 ± 9 years; male 55%; ejection fraction of 48% ± 16). The mean diagnostic delay between HF and ATTR-CM diagnosis was 1.8 years. Besides HF and cardiomyopathy-related phenotypes, the strongest cardiac predictor was atrial fibrillation (AF; 72% in ATTR-CM vs. 60% in non-ATTR-CM, P = 0.02), whereas the strongest non-cardiac predictor was carpal tunnel syndrome (21% in ATTR-CM vs. 3% in non-ATTR-CM, P < 0.001). The strongest combination predictor was AF, joint disorders, and HF with preserved ejection fraction (29% in ATTR-CM vs. 18% in non-ATTR-CM: odds ratio = 2.03, 95% confidence interval = 1.28-3.22). CONCLUSIONS: Not only well-known variables associated with ATTR-CM but also unique combinations of cardiac and non-cardiac phenotypes are able to predict ATTR-CM in a real-world HF population, aiding in early identification of ATTR-CM patients.
Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Heart Failure , Aged , Aged, 80 and over , Humans , Male , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/complications , Cardiomyopathies/diagnosis , Cardiomyopathies/epidemiology , Cardiomyopathies/complications , Delayed Diagnosis , Electronic Health Records , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Failure/complications , Prealbumin/genetics , Retrospective Studies , FemaleABSTRACT
PURPOSE: Transthyretin cardiac amyloidosis (ATTR-CA) is thought to be prevalent in patients with severe aortic stenosis (AS) who are referred for transcatheter aortic valve replacement (TAVR). However, prior studies were published when TAVR was only offered to elderly, inoperable, and high-risk patients. The aim of this study was to reevaluate the prevalence of ATTR-CA in a contemporary TAVR population and identify high-risk features to guide referral for technetium-99 pyrophosphate scan (99mTc-PyP scan) screening. METHODS: Patients seen in a multidisciplinary TAVR clinic for severe AS 70 years and older were referred for a 99mTc-PyP scan to evaluate for ATTR-CA. The primary outcome was the percent with a positive scan. The discriminatory ability of high-risk features was assessed to develop a more judicious screening system. RESULTS: Over the study period, 380 patients underwent screening, and 20 patients (5.3%) had a positive scan, with 17 patients having confirmed ATTR-CA, 1 patient deferring confirmatory testing (combined 4.7%), 1 having light chain amyloidosis, and 1 negative on biopsy. Compared to other patient and echocardiographic measures, elevated NT-pro BNP (> 1000 ng/L) was the best discriminator on who should be referred for 99mTc-PyP scan screening, with a sensitivity of 90% and a negative predictive value of 99%. CONCLUSION: The prevalence of ATTR-CA may be lower in a contemporary TAVR population due to its expanded indication for low-risk patients. NT-pro BNP is a simple test that can improve screening yield and more judiciously guide screening for ATTR-CA in this at-risk population. Comparison of the original versus the proposed algorithm.
Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Transcatheter Aortic Valve Replacement , Humans , Aged , Amyloid Neuropathies, Familial/diagnostic imaging , Amyloid Neuropathies, Familial/epidemiology , Cardiomyopathies/diagnostic imaging , Prevalence , Radionuclide Imaging , PrealbuminABSTRACT
Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF) among patients ≥60 years of age. Although the V122I (valine to isoleucine substitution at position 122 of the transthyretin protein) variant associated with hereditary ATTR-CM is present in 3.4% of self-identified Black individuals in the United States (or 1.5 million people), the phenotypic penetrance is not known. Methods and Results The SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) study is a currently accruing prospective multisite study designed to determine the prevalence of ATTR-CM using technetium-99m-pyrophosphate imaging in older (≥60 years of age) self-identified Black and Hispanic individuals with HF. Calculations of the penetrance and prevalence of the V122I allele, along with analyses of functional, biochemical, and echocardiographic parameters, were performed for the first 278 Black participants in SCAN-MP. The prevalence of ATTR-CM was 6.8% (95% CI, 4.2-10.5; n=19 cases), of whom 63% were ATTR wild-type. The prevalence of V122I was 6.5% (n=18 carriers), of whom 7 had ATTR-CM, yielding a phenotypic penetrance of 39% (95% CI, 17-64). V122I carriers with ATTR-CM evidenced more advanced HF than carriers without ATTR-CM. Prealbumin concentration was lowest among V122I carriers with ATTR-CM (12.9 mg/dL) versus carriers without ATTR-CM (21.0 mg/dL) and HF controls (25.0 mg/dL, P<0.0001). Conclusions Among older Black individuals with HF and increased left ventricular wall thickness, of those with ATTR-CM, 63% had wild-type, and of those with V122I, the phenotypic penetrance of ATTR-CM was 39% (95% CI, 17-64), suggesting that genotype alone is insufficient for diagnosis. Prealbumin concentration may be useful to identify V122I carriers with ATTR-CM. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03812172.
Subject(s)
Amyloid Neuropathies, Familial , Amyloidosis , Cardiomyopathies , Heart Failure , Aged , Humans , Amyloid Neuropathies, Familial/diagnostic imaging , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/genetics , Amyloidosis/metabolism , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/epidemiology , Cardiomyopathies/genetics , Health Disparate Minority and Vulnerable Populations , Heart Failure/diagnostic imaging , Heart Failure/epidemiology , Penetrance , Prealbumin/genetics , Prealbumin/metabolism , Prospective StudiesABSTRACT
To determine the prevalence of myocardial uptake (MU) and to identify predictors of MU in patients undergoing scintigraphy. Retrospective single-center series of technetium-99 m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scans performed from March 2017 to March 2020. All patients undergoing scintigraphy were included, except those with preexisting amyloidosis. The features of MU, patients' characteristics and comorbidities were documented. Multivariate analysis was used to find items predicting MU. A total of 3,629 99mTc-DPD scans (total 11,444) were performed in patients aged > 70. The overall prevalence of MU was 2.7% (82/3,629); 1.2% in 2017-2018, to 2% in 2018-2019, and to 3.7% in 2019-2020. The prevalence of MU in patients without suspected cardiomyopathy was 1.2%; 1.1% in 2017-2018, 1.5% in 2018-2019 and 1% in 2019-2020. There is an increase in the number of requests due to suspected cardiomyopathy from 0.2% in 2017-2018 to 1.4% in 2018-2019 and to 4.8% in 2019-2020. Age, male sex, hypertension, heart failure, atrial fibrillation, atrioventricular block, aortic stenosis, and carpal tunnel syndrome were found to be predictors of MU. In patients without heart failure, only age, atrial fibrillation, and carpal tunnel syndrome were predicted MU. The prevalence of MU in scintigraphic studies surged over time due to the incremental referrals under the indication of cardiomyopathy workup. Atrial fibrillation and carpal tunnel syndrome were predictors for MU in patients without heart failure. Identifying patients with MU and no heart failure for extended screening for ATTR can lead to an earlier diagnosis and application of novel treatments.
Subject(s)
Amyloid Neuropathies, Familial , Atrial Fibrillation , Cardiomyopathies , Carpal Tunnel Syndrome , Heart Failure , Humans , Male , Retrospective Studies , Prevalence , Predictive Value of Tests , Amyloid Neuropathies, Familial/diagnostic imaging , Amyloid Neuropathies, Familial/epidemiology , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/epidemiology , Radionuclide ImagingABSTRACT
OBJECTIVE: Hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy, a rare autosomal-dominant disease, has gained attention in recent years owing to treatment improvements. However, epidemiological real-world mega database of nationwide natural history and survival rates, especially with the specific mutation of Ala97Ser, are limited. METHODS: Taiwan National Health Insurance Research Database contains data from over 23 million individuals; Among them, 175 ATTRv amyloidosis patients validated by rare disease registry were enrolled. Multivariable Cox proportional hazard analyses were applied to investigate the association between baseline characteristics and all-cause mortality. FINDINGS: From 2008 to 2020, the annual incidence and prevalence rates of specific mutations (Ala97Ser) leading to ATTRv amyloidosis with polyneuropathy were 0.04-1.14 and 0.04-4.79 per million in Taiwan, respectively. In Taiwan, these patients exhibited male predominance with a mean age at validation of 62.75 years. At the 5th year after validation, patients exhibited a survival rate of approximately 50%, with higher mortality in male patients (hazard ratio [HR]: 2.22, 95% confidence interval [CI]: 1.15-4.31) and patients older at validation (HR: 1.10, 95% CI: 1.06-1.15). The two most common departments in outpatient were neurology and family medicine, and neurology and cardiology in inpatient. The three most common causes of death registered were unspecified amyloidosis (30.6%), organ-limited amyloidosis (20.9%), and neuropathic heredofamilial amyloidosis (9.7%). INTERPRETATION: The annual prevalence rate of specific mutation (Ala97Ser)-dominant ATTRv amyloidosis with polyneuropathy in Taiwan is comparable to the mid- to high-prevalence country level of the research by Schmidt et al. The extraordinarily high mortality, especially among patients older at validation, may reflect the inadequate awareness and the necessity of early intervention with novel disease-modifying regimens.
Subject(s)
Amyloid Neuropathies, Familial , Amyloidosis, Familial , Polyneuropathies , Humans , Male , Middle Aged , Female , Survival Rate , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/genetics , Polyneuropathies/epidemiology , Polyneuropathies/genetics , MutationABSTRACT
Objectives. Hereditary transthyretin amyloidosis caused by the (ATTRv) p. Val142Ile variant is a common cause of cardiac amyloidosis among Western African countries and Afro-Americans populations. However, in recent years, Caucasian patients have been identified in greater numbers, raising the question of whether this variant has been undeappreciated in this population. We now have new cases of cardiac amyloidosis caused by the p.Val142Ile from a center in northern Portugal. In addition, we reviewed and discussed the published data concerning p.Val142Ile in Caucasians. Design. Patients diagnosed with cardiac amyloidosis underwent genetic testing using TTR gene sequencing and their relatives were recommended for genetic counsellingand testing if a pathogenic TTR variant was found. In our center, we reviewed the clinical data of patients who had the p.Val142Ile variant. A review of published cases of p.Val142Ile in Caucasians was also performed, to which our data was compared. Results. We found three ATTRv patients with the p.Val142Ile variant (one homozygotic), all Caucasian males with a median age at diagnosis of 69 years old. All of them had heart failure and arrhythmias. During the follow-up period, two patients died. There were 47 unrelated unrelated Caucasian cases of ATTRv p.Val142Ile variant reported worldwide until May 2022. Conclusions. Our findings add to the mounting evidence that the global prevalence of p.Val142Ile is likely understated. This highlights the importance of the systematic screening of the TTR gene in amyloidosis and phenocopies, as well as larger epidemiologic studies to determine the true ATTRv p.Val142Ile prevalence in non-African communities.
Subject(s)
Amyloid Neuropathies, Familial , Heart Failure , Male , Humans , Aged , Portugal/epidemiology , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/geneticsABSTRACT
The limited available data regarding the prevalence of transthyretin amyloidosis, both for wild-type (ATTRwt) and hereditary form (ATTRv), is inferred from highly selected patients and subsequent extrapolations that limit the comprehension of the clinical disease impact. The Tuscan healthcare system in 2006 developed a web-based rare disease registry, to monitor and profile patients affected by rare diseases. Clinicians belonging to regional validated healthcare data centres can register patients at the diagnosis, with a rigorous approach and distinguishing the types of amyloidosis, i.e., ATTRwt versus ATTRv. Thanks to this data collection method, available from July 2006 and extended with electronic therapy plans related to a diagnosis since May 2017, we analysed prevalence and incidence of ATTR and its subtypes. On November 30th 2022, ATTRwt prevalence in Tuscany is 90.3 per 1,000,000 persons and ATTRv prevalence is 9.5 per 1,000,000 persons, whereas the annual incidence ranges from 14.4 to 26.7 per 1,000,000 persons and from 0.8 to 2.7 per 1,000,000 persons, respectively. The male gender is predominant in both forms. All except one patient showed evidence of cardiomyopathy. This epidemiological data requires attention, not only to increase the effort for the clinical management and earlier diagnosis, but also to underline the need for the disease-specific treatments.
Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Humans , Male , Prealbumin , Prevalence , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/genetics , Cardiomyopathies/diagnosisABSTRACT
BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients are often older and may be at risk for obstructive epicardial coronary artery disease (oeCAD). While ATTR-CM may cause small vessel coronary disease, the prevalence and clinical significance of oeCAD is not well described. METHODS AND RESULTS: The prevalence and incidence of oeCAD and its association with all-cause mortality and hospitalization among 133 ATTR-CM patients with ≥ 1-year follow-up was evaluated. The mean age was 78 ± 9 years, 119 (89%) were male, 116 (87%) had wild-type and 17 (13%) had hereditary subtypes. Seventy-two (54%) patients underwent oeCAD investigations, with 30 (42%) receiving a positive diagnosis. Among patients with a positive oeCAD diagnosis, 23 (77%) were diagnosed prior to ATTR-CM diagnosis, 6 (20%) at the time of ATTR-CM diagnosis, and 1 (3%) after ATTR-CM diagnosis. Baseline characteristics between patients with and without oeCAD were similar. Among patients with oeCAD, only 2 (7%) required additional investigations, intervention or hospitalization after ATTR-CM diagnosis. After a median follow-up of 27 months there were 37 (28%) deaths in the study population, including 5 patients with oeCAD (17%). Fifty-six (42%) patients in the study population required hospitalization, including 10 patients with oeCAD (33%). There was no significant difference in the rates of death or hospitalization among ATTR-CM patients with and without oeCAD, and oeCAD was not significantly associated with either outcome by univariable regression analysis. CONCLUSIONS: While oeCAD is prevalent in ATTR-CM patients, this diagnosis is frequently known at time of ATTR-CM diagnosis and characteristics are similar to patients without oeCAD.
Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Coronary Artery Disease , Humans , Male , Aged , Aged, 80 and over , Female , Prevalence , Coronary Artery Disease/complications , Incidence , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/therapy , Cardiomyopathies/diagnosis , Cardiomyopathies/epidemiology , Cardiomyopathies/therapyABSTRACT
AIM: Epidemiology of wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) remains poorly defined. A better characterization of pathways leading to ATTRwt-CA diagnosis is of key importance, and potentially informative of disease course and prognosis. The aim of this study was to describe the characteristics of contemporary pathways leading to ATTRwt-CA diagnosis, and their potential association with survival. METHODS AND RESULTS: This was a retrospective study of patients diagnosed with ATTRwt-CA at 17 Italian referral centres for CA. Patients were categorized into different 'pathways' according to the medical reason that triggered the diagnosis of ATTRwt-CA (hypertrophic cardiomyopathy [HCM] pathway, heart failure [HF] pathway, incidental imaging or incidental clinical pathway). Prognosis was investigated with all-cause mortality as endpoint. Overall, 1281 ATTRwt-CA patients were included in the study. The diagnostic pathway leading to ATTRwt-CA diagnosis was HCM in 7% of patients, HF in 51%, incidental imaging in 23%, incidental clinical in 19%. Patients in the HF pathway, as compared to the others, were older and had a greater prevalence of New York Heart Association (NYHA) class III-IV and chronic kidney disease. Survival was significantly worse in the HF versus other pathways, but similar among the three others. In multivariate model, older age at diagnosis, NYHA class III-IV and some comorbidities but not the HF pathway were independently associated with worse survival. CONCLUSIONS: Half of contemporary ATTRwt-CA diagnoses occur in a HF setting. These patients had worse clinical profile and outcome than those diagnosed either due to suspected HCM or incidentally, although prognosis remained primarily related to age, NYHA functional class and comorbidities rather than the diagnostic pathway itself.