Potential performance of a 0 h/1 h algorithm and a single cut-off measure of high-sensitivity troponin T in a diverse population: main results of the IN-HOPE study
Authors: de Barros e Silva Pedro G M , Ferreira Ana Amaral , Malafaia Felipe , Tavares Reis Antonielle Figueiredo Macedo , Sznejder Henry , Lopes Junior Augusto Celso De Araujo , Agostinho Camila Anacleto , Fonseca Luiz Henrique de Oliveira , Okitoi Débora Vieira Donini , Correa Celso Musa , Zincone Eduardo , Cury Marcelo Paiva , Rosa Gustavo Augusto Lopes , Ribeiro Henrique Barbosa , Soeiro Alexandre de Matos , de Oliveira Carlos Alexandre Lemes , Kuusberg Guilherme Capelli , Ohe Louis Nakayama , Souza Douglas de Oliveira , Manfredi Adriana Bertolami , Martins Amanda Francisco , Sampaio Pedro Paulo Nogueres , Vaz Thiago Baganha , Franco Luciana Ferreira , Ferreira Carlos Eduardo dos Santos , Lopes Renato Delascio ,   IN-HOPE Investigators, Agostinho Camila Anacleto , de Alcântara Chaud Mariana Silveira , Benedito Luisa Carvalho , Pessanha Raul Cordeiro , Rossi Lais Olivo , Tognoli Rafael Brufatto , Malafaia Felipe Lopes , Lazarte Mireya Raiza Mendonza , Azzolini Roberta Porreca , Sampaio Márcio Campos , Roveri Patricia de Oliveira , de Oliveira Barros Bruno Rayder , Alves Fabio Quartieri , Romualdo Giovana Fioravante , Rabaça Aline Nogueira , Miranda Carolina , Silva Aline Oliveira , Mathieu Aliana Guimaraes , Carvalho Clarissa , de Oliveira Fonseca Luiz Henrique , Pacheco Alessandra Arnez , Medeiros Jessica Rizkalla Corrêa , Porto Luis Fernando Bruzzi , dos Santos Coelho Roberta Pereira , Sant'Anna Pires Susan , Dos Santos Farjala Lilian Maria , Okitoi Débora Vieira Donini , Dias Sarah Isabel Rodrigues , Tavares Ana Isabel Machado , de Freitas Renata Ramos , de Souza Oliveira Neto Kleber Nuno , Fernandes Thiago Andersib , De Nicola Bechara Gabriela Maria , Kawakami Helio , Prata Aline Gesualdo , Carvalho Vessia , Ferreira Juliana Oliveira , do Nascimento Martins Eliana Vieira , da Silva Lima Natalia Muritiba , Damasceno Erika Frias Paulino , Alves Bruno Oliveira , Rodrigues Leonardo Afonso Cortezi , da Silva Gonçalves Mariane Oliveira , dos Santos Valle Said Roberta , Epaminondas Evytuanne Carvalho , Soares Beatriz Nascimento Sampaio , da Silva Sandra Alves , de Lemos Roberta Magalhães , de Lima Gonçalves Katarina Katia Silva , de Santana Renata Garcia Placido , da Silva Maira Massena Pessoa , Castro Alvaro Corado , Escalhuze Christiane , Luiz Tatiane Oliveira , Glorio Andreia Pinheiro , Galaskis Paloma Candian , de Oliveira Camila Januário , de Sousa Amanda Pereira , Guimarães Tatiana , de Souza Patrícia Brito , da Silva Eloá Nascimento , dos Reis Aline Daniela Rangel Lisboa , Zimiani Luciana , Soares Paulo Rogério , Leal Tatiana de Carvalho Andreuci Torres , de Oliveira Silva Filho José Roberto , de Oliveira Juliana Brandão , Pedroso Amanda Paula , Guimarães Eddio Pedro Leveck , Fontainha Fabrício Costa , da Silva Alinemara Jordão Dantas , de Souza Alessandra Brandão , de Melo Ana Carla Fernandes , Faria Débora Pereira Vaccari Eliel , de Oliveira Teixeira Garcia Fabyane , Preusse Glauber , da Silva Juliana Souza , Ferreira Layse Munin , da Silva Paloma Sousa , De Mello Andrade Perla , Galvão Sandra Maria Freitas , Valério Tatiana Lessa Ocelli , dos Santos Ventura Nunes Vanessa Beatriz , do Nascimento Gomes Wender Charles , Marangoni Matheus Henrique , dos Santos Márcio Augusto , Nakashiro Newton Teruo , Silva Eliete Melo , de Souza Thayza Varanda , Lima Débora Silveira , Rocha Isleid Lima , Vita Natália , de Sales Bicalho Vinicius Vaz , Santos Vitor Sobreira Souza , Gouvea Vinicius Salim , Carvalho Thaysa Louzada , Delamain José Henrique Herrmann , Nunes Murilo Meneses , Prata Mateus Arantes , Paiva Patrícia , Almeida Milena Torres , Viana Renata , Filho Edmundo Vieira Prado , dos Santos Cristiane Ferreira Serra , de Souza Andrea Franco Cavalcante , Caldeira Evelize Pereira , Klepp Anthony Gueratto , Correa Jéssica Tomps , dos Santos Raissa Gabrielle Reis , Cordino Rafaella Araujo , Guimaro Juliana , Reis Andre Augusto Ouro , dos Santos Lima Aline Romélia , Andrade Adriana Ribeiro , Veludo Aline Maria Gomes , Canella Veruska Regina Gava , de Lima Fernanda Gervazoni , Lima Kleber Monteiro , da Silva Tainan Araujo , dos Santos Vanessa , Vilela Cesár , de Souza Lucimar Casemiro , Cabral Gisele , Bressan Paulo Ricardo Castellucci , Rodrigues Victor Ales , de Assis Dayanne Lopes Chaves , de Souza Anderson Martins 
Published: July 2023

Abstract

Aims
Chest pain is a major cause of medical evaluation at emergency department (ED) and demands observation to exclude the diagnosis of acute myocardial infarction (AMI). High-sensitivity cardiac troponin assays used as isolated measure and by 0- and 1-h algorithms are accepted as a rule-in/rule-out strategy, but there is a lack of validation in specific populations.

Methods and results
The IN-HOspital Program to systematizE Chest Pain Protocol (IN-HOPE study) is a multicentre study that prospectively included patients admitted to the ED due to suspected symptoms of AMI at 16 sites in Brazil. Medical decisions of all patients followed the standard approach of 0 h/3 h protocol, but, in addition, blood samples were also collected at 0 and 1 h and sent to a central laboratory (core lab) to measure high-sensitivity cardiac troponin T (hs-cTnT). To assess the theoretical performance of 0 h/1 h algorithm, troponin &lt; 12 ng/L with a delta &lt; 3 was considered rule-out while a value ≥ 52 or a delta ≥ 5 was considered a rule-in criterion (the remaining were considered as observation group). The main objective of the study was to assess, in a population managed by the 0 h/3 h protocol, the accuracy of 0 h/1 h algorithm overall and in groups with a higher probability of AMI. All patients were followed up for 30 days, and potential events were adjudicated. In addition to the prospective cohort, a retrospective analysis was performed assessing all patients with hs-cTnT measured during the year of 2021 but not included in the prospective cohort, regardless of the indication of the test. A total of 5.497 patients were included (583 in the prospective and 4.914 in the retrospective analysis). The prospective cohort had a mean age of 57.3 (± 14.8) and 45.6% of females with a mean HEART score of 4.0 ± 2.2. By the core lab analysis, 74.4% would be eligible for a rule-out approach (45.3% of them with a HEART score &gt; 3) while 7.3% would fit the rule-in criteria. In this rule-out group, the negative predictive value for index AMI was 100% (99.1–100) overall and regardless of clinical scores. At 30 days, no death or AMI occurred in the rule-out group of both 0/1 and 0/3 h algorithms while 52.4% of the patients in the rule-in group (0 h/1 h) were considered as AMI by adjudication. In the observation group (grey zone) of 0 h/1 h algorithm, GRACE discriminated the risk of these patients better than HEART score. In the retrospective analysis, 1.091 patients had a troponin value of &lt;5 ng/L and there were no cardiovascular deaths at 30 days in this group. Among all 4.914 patients, the 30-day risk of AMI or cardiovascular death increased according to the level of troponin: 0% in the group &lt; 5 ng/L, 0.6% between 5 and 14 ng/L, 2.2% between 14 and 42 ng/L, 6.3% between 42 and 90 ng/L, and 7.7% in the level ≥ 90 ng/L.

Conclusion
In this large multicentre study, a 0 h/1 h algorithm had the potential to classify as rule-in or rule-out in almost 80% of the patients. The rule-out protocol had high negative predictive value regardless of clinical risk scores. Categories of levels of hs-cTn T also showed good accuracy in discriminating risk of the patients with a very favourable prognosis for cardiovascular death in the group with value &lt; 5 ng/L.

ClinicalTrials.gov
NCT04756362