Acute Myocardial Infarction and Percutaneous Coronary Intervention: What does the Epidemiological Data of the Last Years Indicate?

Abstract Background: ST-segment elevation acute myocardial infarction (STEMI) is a pathological process that involves cardiac muscle tissue death. Intravenous thrombolysis with fibrinolytics or primary percutaneous coronary intervention (PCI), an invasive technique, can be performed for tissue revascularization. PCI has been preferred as compared to non-invasive methods, although few studies have described its use in Brazil. Objectives: The aim of the present study was to analyze data on the use of primary PCI and investigate the relevance of hospitalizations for the treatment of STEMI in the country. Methods: A descriptive, cross-sectional analysis of data from the Brazilian Unified Health system (SUS) Department of Informatics (DATASUS) from 2010 to 2019 was conducted. Results: Hospitalizations for STEMI represented 0.6% of all hospital admissions in Brazil in the analyzed period, 0.9% of hospital costs, and 2.1% of deaths. The number of hospitalizations due to STEMI was 659,811, and 82,793 for PCIs. Length of hospital stay was 36.0% shorter and mortality rate was 53.3% lower in PCI. The mean cost of PCI was 3.5-fold higher than for treatment of STEMI. Conclusions: Data on hospitalizations for STEMI treatment in Brazil revealed high hospitalization and mortality rates, elevated costs, and long hospital stay. Although primary PCI is a more expensive and less used technique than other methods, it can reduce the length of hospital stay and mortality in the treatment of STEMI.

Influence of Factors Affecting Quality of Life on in-Hospital Cardiovascular Events of Patients with Acute Myocardial Infarction with and without ST-segment Elevation

Abstract Background Acute myocardial infarction (AMI), with and without ST-segment elevation (STEMI and NSTEMI, respectively), is the principal cause of cardiovascular morbidity and mortality in Brazil and around the world. Modifiable risk factors (RF) and quality of life (QOL) may correlate with the type of AMI. Objective To evaluate the influence of QOL and RF on the type of AMI and in-hospital cardiovascular events in STEMI and NSTEMI patients. Methods This was an observational, cross-sectional study. Patients with AMI attending four referral hospitals (three private and one public) for cardiovascular disease treatment were assessed for QOL using the Brazilian version of the 36-item short form survey. A p < 0.05 was considered statistically significant. Results We evaluated 480 volunteers; 51% were treated in one of the private hospitals. In total, 55.6% presented with STEMI, and 44.4% with NSTEMI. Patients from the public hospital were 8.56 times more likely to have STEMI compared to those from the private hospitals. There was a higher prevalence of smokers in STEMI (p < 0.028) patients. QOL was not associated with the type of AMI. A negative patient perception of the physical health and pain domains was observed. Although a significant difference between the physical and the mental health domains was not observed, individual domains were correlated with some in-hospital outcomes. Conclusion There was a higher prevalence of smokers among individuals with STEMI. Domains of QOL showed a statistically significant relationship with the occurrence of in-hospital cardiovascular events, with no difference between the types of AMI.

Tempos de atendimento e desfechos no infarto agudo do miocárdio com supradesnivelamento ST / Time of care and outcomes in ST-segment elevation myocardial infarction

Objetivo: Comparar os tempos de tratamento dor-porta e porta-balão em indivíduos com infarto agudo do miocárdio com supradesnivelamento ST com os desfechos cardiovasculares em 30 dias. Métodos: Trata-se de uma coorte histórica, realizada por meio da pesquisa de prontuários eletrônicos e dos bancos de dados já existentes dos serviços de hemodinâmica de todos os indivíduos atendidos com diagnóstico de infarto agudo do miocárdio com supradesnivelamento ST e submetidos à angioplastia, no período de março de 2015 a setembro de 2016, em dois hospitais públicos de grande porte de Porto Alegre (RS). Os desfechos foram o óbito intra-hospitalar e em 30 dias e os eventos cardíacos maiores hospitalares e em 30 dias. Resultados: Foram avaliadas as informações de 808 indivíduos, sendo 26,9% provenientes do Hospital de Clínicas de Porto Alegre e 73,1% do Instituto de Cardiologia ­ Fundação Universitária de Cardiologia. Não houve diferença significativa na caracterização da amostra. Um terço dos indivíduos analisados apresentou tempo dor- -porta menor ou igual a 180 minutos, e 72% tiveram tempo porta-balão menor que 90 minutos. A mediana do tempo total de isquemia foi de 338 minutos. Na avaliação dos tempos não houve diferença significativa entre os dois hospitais. Para eventos cardíacos maiores e óbitos intra- -hospitalares, o único tempo que se mostrou significativo, após o ajuste multivariado, foi o porta-balão, em que os indivíduos com tempo maior que 90 minutos apresentaram razão de risco de 1,06 (IC95% 1,02-1,11) e 5,78 (IC95% 1,44-23,2), respectivamente, para eventos cardíacos maiores e óbitos intra-hospitalares. Para eventos cardíacos maiores total e óbito total, nenhum dos três tempos se associou significativamente com o desfecho após ajuste. Contudo, o tempo porta-balão maior ou igual a 90 minutos também foi significativo para razão de risco bruto para ambos, assim como a dor-porta para óbito total. Conclusão: Os dados da pesquisa corroboram as recomendações internacionais para cumprimento dos menores tempos de atendimento, em especial do tempo porta-balão, para o bom prognóstico. Infelizmente, no país, o tempo de isquemia miocárdica ainda está muito aquém do ótimo, necessitando de melhorias na área para melhorar os desfechos nesses indivíduos.

Objective: To compare symptom-onset-to-door and door- -to-balloon times in individuals with ST-segment elevation myocardial infarction to the 30-day cardiovascular outcomes. Methods: This is a historical cohort, using electronic medical records and the existing databases of hemodynamic services of all individuals diagnosed with ST-segment elevation myocardial infarction undergoing angioplasty between March 2015 and September 2016, in two large public hospitals in Porto Alegre. The outcomes were in-hospital death and death in 30 days, and major adverse cardiac events in hospital and in 30 days. Results: The information of 808 patients was evaluated, with 26.9% from Hospital de Clínicas de Porto Alegre, and 73.1% from the Instituto de Cardiologia ­ Fundação Universitária de Cardiologia. There was no significant difference in the characterization of the sample. One-third of the individuals evaluated presented symptom-onset-to-door of 180 minutes or less, and 72% had door-to- -balloon time below 90 minutes. The median total ischemic time was 338 minutes. In the evaluation of the times, there was no significant difference between the two hospitals. For more major cardiac events and intra-hospital deaths, the only time that proved to be significant after the multivariate adjustment was the door-to-balloon time, in which individuals with time higher than 90 minutes had a risk ratio of 1.06 (95% CI 1.02-1.11) for major cardiac events and 5.78 (95% CI 1.44-23.2), for intra-hospital deaths. For total major adverse cardiac events and total death, none of the 3 times was significantly associated with the outcome after adjustment; however, door-to-balloon of 90 minutes or more was also significant for crude risk ratio for both, as well as symptom-onset-to-door for total death. Conclusion: The research data corroborate the international recommendations to meet shorter service times, especially door-to-balloon time, for a good prognosis. Unfortunately, in the country, the time of myocardial ischemia is still far from optimal, requiring improvement in the area to improve the outcomes in these individuals.

Impacto de las políticas de salud en la incidencia de reperfusión de infarto agudo de miocardio durante el inicio de la pandemia por COVID-19 en Uruguay / Impact of public health policies on the incidence of acute myocardial reperfusion during the initial stages of the COVID-19 pandemic in Uruguay / Impacto das políticas de saúde na incidência de infarto do miocárdio durante a pandemia de COVID-19 no Uruguai

Introducción: las medidas sanitarias de emergencia impuestas para contener el SARS-CoV-2 pueden tener efectos colaterales en la atención de enfermedades cardiovasculares. Los datos mundiales de los países sobre la incidencia de infarto agudo de miocardio con elevación del segmento ST (IAMCEST) durante la pandemia son fundamentales para la política sanitaria futura. Objetivos: nuestro objetivo fue determinar si las medidas sanitarias de emergencia impuestas en Uruguay tuvieron un impacto directo en la calidad de la atención en la reperfusión del IAMCEST. Métodos: realizamos un estudio retrospectivo poblacional de todo el país para determinar la incidencia de reperfusión de IAMCEST (fibrinolíticos e intervención coronaria percutánea, FBL e ICP respectivamente) durante el período sanitario de emergencia. La tasa de incidencia de la reperfusión, el tiempo hasta la reperfusión y la mortalidad asociada se recopilaron de la base de datos del Fondo Nacional de Recursos (organización gubernamental única a cargo de la financiación de la reperfusión del IAMCEST en Uruguay). Estos mismos datos se recuperaron para 2019, 2018 y 2017. Resultados: se trataron durante el periodo de estudio del 2020 (136 pacientes) en comparación con 2019 (180 pacientes), 2018 (182 pacientes) y 2017 (174 pacientes). Se realizó FBL como tratamiento único en 5,1%, 7,2%, 7,7% y 12,1%, respectivamente. La razón de tasa de incidencia de IAMCEST durante el período estudiado en 2020 fue de 0,7 (IC95%: 0,59-0,91). La mediana del tiempo hasta la reperfusión fue similar en comparación con 2019, 2018 y 2017 (p = 0,4). No hubieron diferencias en la mortalidad a 15 dias entre los años evaluados.

Introduction: the emergency health measures imposed to contain SARS-CoV-2 can have collateral effects in the care of cardiovascular diseases. Global country data on the incidence of ST acute myocardial infarction during the pandemic are critical for future health policy. Objectives: our objective was to determine if the emergency health measures imposed in Uruguay had a direct impact on the quality of ST elevation acute myocardial infarction care. Methods: we carried out a population-based retrospective study of the entire country to determine the incidence of reperfusion of ST elevation acute myocardial infarction (fibrinolytic and percutaneous) during the emergency health period. The incidence rate of reperfusion, time to reperfusion, and associated mortality were collected from the Fondo Nacional de Recursos (the only government organization in charge of the reperfusion of ST elevation myocardial infarction in Uruguay). These same data were recovered for 2019, 2018 and 2017. Results: fewer patients were treated in 2020 (136 patients) compared to 2019 (180 patients), 2018 (182 patients), and 2017 (174 patients). Fibrinolytics was performed as the only treatment in 5.1%, 7.2%, 7.7% and 12.1% respectively. The proportion in incidence rate of ST elevation myocardial infarction during the study period in 2020 was lower (0.74, 95% CI: 0.59-0.91). The median time to reperfusion was similar compared to 2019, 2018, and 2017 (p = 0.4). Mortality at 15 days was similar in 2017 (8%), 2018 (6%), 2019 (11%) and 2020 (8%). Conclusion: emergency health measures were associated with a decrease in the incidence of reperfusion of ST elevation myocardial infarction without affecting the time to reperfusion and mortality.

Introdução: as medidas emergenciais de saúde impostas para conter o SARS-CoV-2 podem ter efeitos colaterais no cuidado das doenças cardiovasculares. Os dados globais do país sobre a incidência de infarto agudo do miocárdio durante a pandemia são essenciais para a futura política de saúde. Objetivos: nosso objetivo foi determinar se as medidas de saúde de emergência impostas no Uruguai tiveram um impacto direto na qualidade do atendimento infarto agudo do miocárdio. Métodos: foi realizado um estudo retrospectivo de base populacional em todo o país para determinar a incidência de reperfusão do infarto agudo do miocárdio (fibrinolítico e percutâneo) durante o período de emergência de saúde. A taxa de incidência de reperfusão, tempo de reperfusão e mortalidade associada foram coletados do Fondo Nacional de Recursos (a única organização governamental responsável pela reperfusão de infarto agudo do miocárdio no Uruguai). Esses mesmos dados foram recuperados para 2019, 2018 e 2017. Resultados: menos pacientes foram tratados em 2020 (136 pacientes) em comparação com 2019 (180 pacientes), 2018 (182 pacientes) e 2017 (174 pacientes). Fibrinolisis foi realizado como o único tratamento em 5,1%, 7,2%, 7,7% e 12,1%, respectivamente. A proporção na taxa de incidência de infarto agudo do miocárdio durante o período estudado em 2020 foi menor (0,74, IC 95%: 0,59-0,91). O tempo médio para reperfusão foi semelhante em comparação com 2019, 2018 e 2017 (p = 0,4). A mortalidade em 15 dias foi semelhante em 2017 (8%), 2018 (6%), 2019 (11%) e 2020 (8%). Conclusão: as medidas emergenciais de saúde foram associadas à diminuição da incidência de reperfusão do infarto agudo do miocárdio, sem afetar o tempo de reperfusão e a mortalidade.

Hospitalização por Infarto Agudo do Miocárdio: Um Registro de Base Populacional / Hospitalization for Acute Myocardial Infarction: A Population-Based Registry

Resumo Fundamento: O infarto agudo do miocárdio com supradesnivelamento do segmento ST (STEMI) é uma das principais apresentações clínicas da cardiopatia isquêmica. Dados de base populacional são relevantes para entendimento contemporâneo da epidemiologia da doença. Objetivo: Descrever incidência, manejo terapêutico, desfechos clínicos hospitalares e eventos cardiovasculares do primeiro ano de seguimento dos indivíduos hospitalizados por STEMI. Métodos: Estudo de coorte prospectiva de base populacional com registro consecutivo das hospitalizações por STEMI em uma cidade do Sul do Brasil entre 2011 e 2014. Foram incluídos indivíduos com STEMI que apresentaram sintomas de isquemia miocárdica aguda nas últimas 72 horas. Os valores de p < 0,05 foram considerados significativos. Resultados: A incidência anual de hospitalizações por STEMI foi de 108 casos por 100.000 habitantes. A incidência ajustada foi maior entre os mais velhos (risco relativo 64,9; IC95% 26,9 - 156,9; p para tendência linear < 0,001) e entre os homens (risco relativo 2,8; IC95% 2,3 - 3,3; p < 0,001). Ocorreram 530 hospitalizações durante o período avaliado e a taxa de reperfusão foi de 80,9%. A mortalidade hospitalar e a taxa de eventos cardiovasculares em 1 ano foram, respectivamente, 8,9% e 6,1%. Os mais velhos apresentaram maior mortalidade hospitalar (risco relativo 3,72; IC95% 1,57 - 8,82; p para tendência linear = 0,002) e mais eventos cardiovasculares em 1 ano (hazard ratio 2,35; IC95% 1,12 - 4,95; p = 0,03). Conclusão: Este registro demonstra abordagem terapêutica e mortalidade hospitalar semelhante às observadas em países desenvolvidos. Entretanto, a taxa de hospitalizações foi maior comparada com esses países.

Abstract Background: ST-segment elevation myocardial infarction (STEMI) is one of the main clinical manifestations of ischemic heart disease. Population-based data are relevant to better understand the current epidemiology of this condition. Objective: To describe the incidence, therapeutic management, hospital clinical outcomes and cardiovascular events in the first year of follow-up of individuals hospitalized for STEMI. Methods: Population-based prospective cohort study with consecutive registries of hospitalization for STEMI in a city in southern Brazil from 2011 to 2014. It included patients with STEMI who presented acute myocardial ischemia symptoms in the last 72 hours. A p-value < 0.05 was considered significant. Results: The annual incidence of STEMI hospitalizations was 108 cases per 100,000 inhabitants. Adjusted incidence was higher among older individuals (relative risk 64.9; 95% CI 26.9-156.9; p for linear trend < 0.001) and among men (relative risk 2.8; 95% CI 2.3-3.3; p < 0.001). There were 530 hospitalizations in the period under evaluation and the reperfusion rate reached 80.9%. Hospital mortality and the one-year follow-up cardiovascular event rate were, respectively, 8.9% and 6.1%. The oldest patients had higher hospital mortality (relative risk 3.72; 95% CI 1.57-8.82; p for linear trend = 0.002) and more one-year follow-up cardiovascular events (hazard ratio 2.35; 95% CI 1.12-4.95; p = 0.03). Conclusion: This study shows that both the therapeutic approach and hospital mortality are similar to the ones found in developed countries. However, the hospitalization rate was higher in these countries.

Reperfusión fármaco-invasiva en el manejo del infarto agudo de miocardio en Chile: un llamado a la acción / Pharmaco-invasive reperfusion in acute myocardial infarction in Chile: a call for action

Resumen En Chile, se han logrado avances importantes en el manejo del Infarto Agudo de Miocardio (IAM) con elevación del segmento ST (IAMCEST). Debido a la mejoría en el diagnóstico precoz y tratamiento, particularmente, con el incremento de la Angioplastía Primaria (APP), hoy están dadas las condiciones para seguir progresando por la vía de la combinación de estrategias de reperfusión y la creación de Redes de Manejo del IAM. El siguiente artículo revisa la evidencia que justifica impulsar dicho avance y se esbozan posibles caminos para lograrlo.

Abstract In Chile, important advances have been made in the management of Acute Myocardial Infarction (MI) with ST segment elevation (STEMI). Due to the progress in early diagnosis and treatment, particularly with the increase in Primary Angioplasty (Primary PCI), nowadays there are conditions to improve early management through the combination of reperfusion strategies and the implementation of MI reperfusion networks. The present article reviews the evidence justifying the promotion of this strategy and outlines possible actions to achieve it.

Características epidemiológicas del infarto de miocardio con elevación del segmento ST en Perú: resultados del PEruvian Registry of ST-segment Elevation Myocardial Infarction (PERSTEMI) / Epidemiological characteristics of ST-segment elevation myocardial infarction in Peru: Results of the PEruvian Registry of ST-segment Elevation Myocardial Infarction (PERSTEMI)

Resumen Objetivo: Determinar las características epidemiológicas, el tratamiento, las estrategias de reperfusión y los eventos adversos intrahospitalarios de pacientes con infarto de miocardio con elevación del segmento ST en Perú. Métodos: Estudio observacional, prospectivo, multicéntrico a nivel nacional, en pacientes mayores de 18 años hospitalizados con diagnóstico de infarto de miocardio con elevación del segmento ST. Resultados: Desde febrero de 2016 a febrero de 2017, 396 pacientes fueron enrolados; la edad promedio fue de 64.9 ± 12 años y el 21% eran mujeres. En las primeras 12 h de evolución un 38% fueron fibrinolisados, en un 29% se realizó PCI primaria y un 33% no recibieron reperfusión. En el 12.9% se usó estrategia farmacoinvasiva. La tasa de éxito de la fibrinólisis fue de un 65% y la de la PCI primaria fue de un 82%. La estancia hospitalaria fue de 6 días (RIQ 5-10). La mortalidad intrahospitalaria llegó a un 10.1%, siendo la principal causa de muerte el choque cardiogénico. La tasa de reinfarto intrahospitalario fue de 2.2% y de falla cardiaca postinfarto, de 25%. La edad > 75 años, grandes tamaños de infarto, la fracción de eyección de ventrículo izquierdo < 40% y la ausencia de ondas T negativas en el electrocardiograma posreperfusión fueron variables relacionadas de manera independiente con una mayor mortalidad intrahospitalaria. Conclusiones: El infarto de miocardio con elevación del segmento ST en Perú afecta con más frecuencia a varones de entre 60 y 70 años. El tratamiento de reperfusión inicial más frecuente es la fibrinólisis, seguida por la angioplastia primaria y la estrategia farmacoinvasiva. El motivo principal de la falta de administración de tratamiento de reperfusión fue la demora desde el inicio de los síntomas hasta el primer contacto médico. La causa más frecuente de muerte intrahospitalaria es el choque cardiogénico.

Abstract Objective: To determine the epidemiological characteristics, treatment, reperfusion strategies and in-hospital adverse events of patients with ST elevation myocardial infarction in Peru. Methods: Observational, prospective multicentre study in patients over 18 years admitted to hospital with a diagnosis of ST elevation myocardial infarction. Results: A total of 396 patients were enrolled in the registry during February 2016 to February 2017. The mean age was 64.9 ± 12 years, and 21% were women. In the first 12 h of onset 38% of patients were fibrinolysed, 29% underwent primary PCI, and 33% did not receive any reperfusion. Pharmaco-invasive strategy was used in 12.9% of cases. The fibrinolysis was successful in 65% of patients, and primary PCI success was 82%. The hospital stay was 6 days (IQR 5-10). In-hospital mortality was 10.1%, with the first cause of death being due to cardiogenic shock. The rate of in-hospital re-infarction was 2.2%, and the rate of acute heart failure was 25%. Age > 75 years, large infarct size, left ventricular ejection fraction < 40%, and absence of negative T waves on post-reperfusion electrocardiogram were independently related to higher in-hospital mortality. Conclusions: In Peru, ST elevation myocardial infarction most frequently affects men between 60-70 years. The most frequent initial reperfusion treatment is fibrinolysis, followed by primary angioplasty, and pharmaco-invasive strategy. The main reason for the lack of administration of reperfusion treatment was the delay from symptoms onset to first medical contact. The most common cause of in-hospital death was cardiogenic shock.

Paradoxo dos fatores de risco na ocorrência de parada cardiorrespiratória em pacientes com síndrome coronária aguda / Risk factor paradox in the occurrence of cardiac arrest in acute coronary syndrome patients

RESUMO Objetivo: Comparar pacientes admitidos com síndrome coronariana aguda sem prévia identificação de fatores de risco cardiovascular com pacientes que portavam um ou mais fatores de risco. Métodos: Análise retrospectiva dos pacientes admitidos com o primeiro episódio de síndrome coronariana aguda sem cardiopatia prévia, incluídos em um registro nacional de síndrome coronariana aguda. Os pacientes foram divididos segundo o número de fatores de risco: nenhum fator de risco (G0), um ou dois fatores de risco (G1 - 2) e três ou mais fatores de risco (G ≥ 3). Realizou-se uma análise comparativa entre os três grupos e se estudaram os preditores independentes de parada cardíaca e óbito. Resultados: O total apurado foi de 5.518 pacientes, 72,2% deles do sexo masculino, com média de idade de 64 ± 14 anos. O G0 teve uma incidência maior de infarto do miocárdio com elevação do segmento ST, sendo o vaso mais frequentemente envolvido a artéria descendente anterior esquerda, e menor prevalência de envolvimento de múltiplos vasos. Embora o G0 tivesse uma classe Killip mais baixa (96% Killip I; p < 0,001) e maior fração de ejeção (G0: 56 ± 10% versus G1 - 2 e G ≥ 3: 53 ± 12%; p = 0,024) na admissão, houve incidência significantemente maior de parada cardíaca. A análise multivariada identificou ausência de fatores de risco como um fator independente para parada cardíaca (OR 2,78; p = 0,019). A mortalidade hospitalar foi ligeiramente maior no G0, embora sem significância estatística. Segundo a análise de regressão de Cox, o número de fatores de risco não se associou com mortalidade. Os preditores de óbito em 1 ano de seguimento foram infarto do miocárdio com elevação do segmento ST (OR 1,05; p < 0,001) e fração de ejeção inferior a 50% (OR 2,34; p < 0,001). Conclusão: Embora o grupo sem fatores de risco fosse composto de pacientes mais jovens e com menos comorbidades, melhor função ventricular esquerda e coronariopatia menos extensa, a ausência de fatores de risco foi um preditor independente de parada cardíaca.

ABSTRACT Objective: To compare patients without previously diagnosed cardiovascular risk factors) and patients with one or more risk factors admitted with acute coronary syndrome. Methods: This was a retrospective analysis of patients admitted with first episode of acute coronary syndrome without previous heart disease, who were included in a national acute coronary syndrome registry. The patients were divided according to the number of risk factors, as follows: 0 risk factor (G0), 1 or 2 risk factors (G1 - 2) and 3 or more risk factors (G ≥ 3). Comparative analysis was performed between the three groups, and independent predictors of cardiac arrest and death were studied. Results: A total of 5,518 patients were studied, of which 72.2% were male and the mean age was 64 ± 14 years. G0 had a greater incidence of ST-segment elevation myocardial infarction, with the left anterior descending artery being the most frequently involved vessel, and a lower prevalence of multivessel disease. Even though G0 had a lower Killip class (96% in Killip I; p < 0.001) and higher ejection fraction (G0 56 ± 10% versus G1 - 2 and G ≥ 3 53 ± 12%; p = 0.024) on admission, there was a significant higher incidence of cardiac arrest. Multivariate analysis identified the absence of risk factors as an independent predictor of cardiac arrest (OR 2.78; p = 0.019). Hospital mortality was slightly higher in G0, although this difference was not significant. By Cox regression analysis, the number of risk factors was found not to be associated with mortality. Predictors of death at 1 year follow up included age (OR 1.05; p < 0.001), ST-segment elevation myocardial infarction (OR 1.94; p = 0.003) and ejection fraction < 50% (OR 2.34; p < 0.001). Conclusion: Even though the group without risk factors was composed of younger patients with fewer comorbidities, better left ventricular function and less extensive coronary disease, the absence of risk factors was an independent predictor of cardiac arrest.