RESUMO

BACKGROUND: Transthyretin amyloidosis (ATTR) is a progressive, fatal disease caused by toxic misfolded transthyretin (TTR) amyloid deposits. Patisiran, an RNA interference therapeutic, inhibits synthesis of wild-type and variant TTR and is approved for the treatment of hereditary ATTR with polyneuropathy. OBJECTIVE: Describe efficacy and safety of patisiran in patients from Brazil with ATTR cardiomyopathy (ATTR-CM) via a post hoc subgroup analysis of the global APOLLO-B study (NCT03997383). METHODS: Patients 18­85 years of age with ATTR-CM and heart failure were randomized 1:1 to patisiran 0.3 mg/kg or placebo every 3 weeks for 12 months. Primary endpoint was change from baseline (CFB) in functional capacity (6-minute walk test) at Month 12 for patisiran vs placebo. Secondary endpoints included CFB to Month 12 in health status and quality of life (Kansas City Cardiomyopathy QuestionnaireOverall Summary [KCCQ-OS]). Exploratory endpoints included CFB in cardiac biomarkers and Perugini grade by Tc-99m scintigraphy, the latter assessed in a subset of patients in an imaging study within APOLLO-B. RESULTS: Of 360 patients in APOLLO-B, 42 were from Brazil (patisiran, n=20; placebo, n=22): median (range) age at screening, 73 (51, 85) years; male, 81%; wild-type ATTR, 54.8%. No patients were receiving tafamidis at baseline. Patisiran showed benefit vs placebo in 6-minute walk test (median [95% CI] CFB [meters]: −2.02 [−58.5, 42.9] vs −30.1 [−72.2, 3.5]; HodgesLehmann estimate of median difference [95% CI]: 31.4 [−16.6, 79.4]; Figure 1A) and in KCCQ-OS (least squares mean [SEM] CFB: 9.4 [3.8] vs 2.6 [3.7]; least squares mean difference [SEM]: 6.8 [5.3]; Figure 1B). Death was reported in 0 patisiran patients vs 3 (13.6%) placebo. The ratio of adjusted geometric mean fold-change (patisiran:placebo [95% CI]) was 0.77 (0.57, 1.03) for NT-proBNP and 0.87 (0.68, 1.12) for troponin I. In the imaging subset (n=35), 11/18 (61.1%) patisiran patients improved Perugini grade vs 0/10 placebo at Month 12 (Figure 2). Few patisiran patients experienced serious (8 [40%]) or severe (4 [20%]) adverse events; none were drug related. CONCLUSION: In Brazilian patients with ATTR-CM, potential benefit was observed with patisiran on functional capacity, health status and quality of life, cardiac biomarkers, and Perugini grade, consistent with data from the global APOLLO-B population. The results are descriptive; the study was not powered to detect treatment effects specific to this subgroup.

Assuntos

RESUMO

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

Assuntos

RESUMO

INTRODUÇÃO: A amiloidose transtiretina (ATTR) é uma doença multissistêmica causada pela deposição de proteína fibrilar em órgãos e tecidos. Os genótipos e fenótipos da ATTR são altamente heterogêneos. MÉTODOS: Apresentamos dados sobre sinais e sintomas físicos, avaliações cardíacas e neurológicas, e genética em pacientes incluídos no Registro de Amiloidose Cardíaca Transtiretina no Estado de São Paulo (REACT-SP), Brasil. RESULTADOS: Foram incluídos 644 pacientes, sendo 505 com a forma variante (ATTRv) e 139 com a forma selvagem (ATTRwt). Dezesseis mutações diferentes foram detectadas, sendo as mais comuns Val50Met (48,3%) e V142Ile (40,8%). No geral, mais da metade dos pacientes apresentou envolvimento cardíaco, e a diferença nessa proporção entre os grupos ATTRv e ATTRwt foi significativa (43,9 vs. 89,9%; p<0,001). O fenótipo neurológico também diferiu entre ATTRv e ATTRwt (56,8 vs. 31,7%; p<0,001). O fenótipo misto foi encontrado em 25,6% da população, sem diferença significativa entre as formas de amiloidose. Um grupo de pacientes permaneceu assintomático (10,4%), com uma proporção menor de pacientes assintomáticos no grupo ATTRwt. CONCLUSÕES: Este estudo detalha o espectro clínico e genético de pacientes com ATTR em São Paulo, Brasil. Esta análise preliminar destaca a considerável heterogeneidade fenotípica das manifestações neurológicas e cardíacas em pacientes com ATTR variante e ATTR do tipo selvagem.

Assuntos

RESUMO

PURPOSE OF REVIEW: More than a century since its discovery, the pathogenesis of Chagas heart disease (CHD) remains incompletely understood. The role of derangements in the autonomic control of the heart in triggering malignant arrhythmia before the appearance of contractile ventricular impairment was reviewed. RECENT FINDINGS: Although previous investigations had demonstrated the anatomical and functional consequences of parasympathetic dysautonomia upon the heart rate control, only recently, coronary microvascular disturbances and sympathetic denervation at the ventricular level have been reported in patients and experimental models of CHD, exploring with nuclear medicine methods their impact on the progression of myocardial dysfunction and cardiac arrhythmias. More important than parasympathetic impaired sinus node regulation, recent evidence indicates that myocardial sympathetic denervation associated with coronary microvascular derangements is causally related to myocardial injury and arrhythmia in CHD. Additionally, 123I-MIBG imaging is a promising tool for risk stratification of progression of ventricular dysfunction and sudden death.

Assuntos

RESUMO

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.

Assuntos

RESUMO

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.

Assuntos

RESUMO

Objective: To generate data on the costs associated with the diagnosis and treatment of obstructive ypertrophic cardiomyopathy (HCM) from the perspective of the private health system in Brazil. Methods: A modified Delphi panel including seven different specialists (three clinical cardiologists with experience in obstructive HCM, two hemodynamicists with experience in septal ablation and two cardiac surgeons with expertise in myectomy), from two Brazilian states (São Paulo and Pernambuco), was conducted between August and November 2022. Two rounds of questions about the use of healthcare resources according to the functional class (NYHA I-IV) and a panel in a virtual platform were conducted to obtain the final consensus. Micro-costing defined costs and unit values were determined based on official price lists. Results: The total diagnosis cost per patient was estimated at BRL 11,486.81. The obstructive HCM management costs analysis showed average annual costs per patient of BRL 17,026.74, BRL 19,401.46, BRL 73,310.07, and BRL 94,885.75 for the functional classes NYHA I, NYHA II, NYHA III, and NYHA IV, respectively. The average costs per patient related to procedures in a year were BRL 12,698.53, BRL 13,462.30, BRL 58,841.67, and BRL 75,595.90 for the functional classes NYHA I, II, III, and IV, respectively. Conclusions: The annual costs of HCM management increased according to the functional class, highlighting the need for safe and effective strategies to improve patient's NYHA functional class while promoting a decrease in the need for invasive therapies.

Objetivo: Gerar dados acerca dos custos associados ao diagnóstico e tratamento da cardiomiopatia hipertrófica (CMH) obstrutiva, sob a perspectiva do sistema de saúde privado no Brasil. Métodos: Um painel Delphi modificado incluindo sete especialistas (três cardiologistas clínicos com experiência em CMH obstrutiva, dois hemodinamicistas com experiência em ablação de septo e dois cirurgiões cardíacos com experiência em miectomia) de dois estados brasileiros (São Paulo e Pernambuco) foi conduzido entre agosto e novembro de 2022. Foram realizadas duas rodadas de perguntas acerca da utilização de recursos de acordo com a classe funcional (NYHA I-IV) e uma reunião virtual para obtenção do consenso final. Os custos foram definidos por meio de microcusteio, e os valores unitários foram definidos com base em listas de preço oficiais. Resultados: O custo total do diagnóstico por paciente foi estimado em R$ 11.486,81. A análise de custos de manejo da CMH obstrutiva mostrou custos médios anuais por paciente de R$ 17.026,74, R$ 19.401,46, R$ 73.310,07 e R$ 94.885,75 para as classes funcionais NYHA I, NYHA II, NYHA III e NYHA IV, respectivamente. Os custos médios por paciente relacionados a procedimentos em um ano foram de R$ 12.698,53, R$ 13.462,30, R$ 58.841,67 e R$ 75.595,90 para as classes NYHA I, II, III e IV, respectivamente. Conclusões: Os custos anuais com o manejo da CMH aumentam de acordo com a classe funcional, destacando a necessidade de estratégias seguras e eficazes capazes de melhorar a classe funcional NYHA do paciente, ao mesmo tempo que promove diminuição da necessidade de terapias invasivas.

Assuntos

RESUMO

INTRODUCTION: Amyloidosis is a group of protein misfolding disorders leading to organ damage due to insoluble amyloid fibril deposits • The two primary types of cardiac amyloidosis are light-chain amyloid (AL) and transthyretin (TTR) cardiac amyloidosis • TTR amyloidosis can be hereditary (hATTR) or age-related (wtATTR). It is an often-overlooked cause of heart failure in older adults • Recent studies reveal its prevalence in various patient groups: up to 13% in HFpEF, 16% in aortic stenosis patients undergoing valve replacement, 7-8% in carpal tunnel release surgery, and 17% in some other contexts • ATTR-CM is significant in the context of cardiovascular diseases, a leading global cause of death. OBJECTIVE: This study aimed 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. MATERIALS AND 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 (Figure 1) using a supervised machine learning (Figure 2) model, with data extracted from DATASUS outpatient and inpatient datasets 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 (Figure 3). RESULTS: From 2015 to 2021, the ML model classified 262 hATTR-CM (213 reference hATTR-CIM and 49 hATTR-CM-like) and 1,581 wtATTR-CM (203 reference wtATTR-CM and 1,378 wtATTR-CM-like). 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, with similar procedures performed (Figure 4). Regarding healthcare utilization, hATTR-CM and hATTR-CM-like had similar profiles on proportion of patients with outpatient visits (hATTR-CM 98.0% vs. 92.0% hATTR-CM-like) and different profile related to proportion of hospitalized patients (hATTR-CM 94.4% vs. 32.7% hATTR-CM-like) (Figure 5) • In wtATTR-CM groups, although both proportions on outpatient visits and hospitalizations were similar, the length of stay (LOS) on hospitalizations was different in wtATTR-CM-like (wtATTR-CM median LOS 5.0 (IQR:2.0 - 10.0] vs. median LOS 7.0 [IQR:3.0 - 14.0]). CONCLUSIONS: Our findings may be useful to support decreasing the uncertainties on ATTR-CM population size in Health Technology Assessment appraisals and in the development of healthcare guidelines and policies to address patients' unmet needs and to improve early diagnosis and access to treatment for patients with ATTR-CM in Brazil This study puts a spotlight on the ATTR-CM underdiagnosis in Brazil using a machine learning approach, which can be used as an important tool to support diagnosis improvement.

Assuntos