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.

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 < 12 ng/L with a delta < 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 > 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 <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 < 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 < 5 ng/L. CLINICALTRIALS.GOV: NCT04756362.

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

BACKGROUND: 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 h and 1 h algorithms are accepted as a rule-in/rule-out strategy but there is a lack of validation in specific populations. METHODS: 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 0/3-h protocol but, in addition, blood samples were also collected at 0 and 1 hour and sent to a central laboratory (core lab) to measure high-sensitivity troponin T (hs-cTnT). To assess the theoretical performance of 0/1-h algorithm, troponin < 12 ng/L with a delta <--- 3 was considered rule out while a value ≥ 52 and/or a delta ≥ 5 was considered a rule in criteria (the remaining were considered as observation group). The main objective of the study was to assess, in a population managed by the 0/3-h protocol, the accuracy of 0/1-h algorithm overall and in groups with higher probability of AMI. All patients were followed 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 the indication of the test. RESULTS: 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 HEART score > 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 clinical scores. At 30 days, no death or AMI occurred in the rule-out group of both 0/1 and 0/3-hour while 52.4% of the patients in the rule-in group (0/1-hour) were considered as AMI by adjudication. In the observation group (grey zone) of 0/1- hour algorithm, GRACE discriminated the risk of these patients better than HEART score. In the retrospective analysis, 1.091 patients had a troponin value < 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 < 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. CONCLUSIONS: In this large multicentre study, a 0/1-h algorithm had the potential to classify as rule in or out 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 values < 5 ng/L.

Sonothrombolysis Promotes Improvement in Left Ventricular Wall Motion and Perfusion Scores after Acute Myocardial Infarction. / A Sonotrombólise Promove Melhora dos Índices de Motilidade e Perfusão do Ventrículo Esquerdo após o Infarto Agudo do Miocárdio.

BACKGROUND: It has recently been demonstrated that the application of high-energy ultrasound and microbubbles, in a technique known as sonothrombolysis, dissolves intravascular thrombi and increases the angiographic recanalization rate in patients with ST-segment-elevation myocardial infarction (STEMI). OBJECTIVE: To evaluate the effects of sonothrombolysis on left ventricular wall motion and myocardial perfusion in patients with STEMI, using real-time myocardial perfusion echocardiography (RTMPE). METHODS: One hundred patients with STEMI were randomized into the following 2 groups: therapy (50 patients treated with sonothrombolysis and primary coronary angioplasty) and control (50 patients treated with primary coronary angioplasty). The patients underwent RTMPE for analysis of left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and number of segments with myocardial perfusion defects 72 hours after STEMI and at 6 months of follow-up. P < 0.05 was considered statistically significant. RESULTS: Patients treated with sonothrombolysis had higher LVEF than the control group at 72 hours (50% ± 10% versus 44% ± 10%; p = 0.006), and this difference was maintained at 6 months of follow-up (53% ± 10% versus 48% ± 12%; p = 0.008). The WMSI was similar in the therapy and control groups at 72 hours (1.62 ± 0.39 versus 1.75 ± 0.40; p = 0.09), but it was lower in the therapy group at 6 months (1.46 ± 0.36 versus 1.64 ± 0.44; p = 0.02). The number of segments with perfusion defects on RTMPE was similar in therapy and control group at 72 hours (5.92 ± 3.47 versus 6.94 ± 3.39; p = 0.15), but it was lower in the therapy group at 6 months (4.64 ± 3.31 versus 6.57 ± 4.29; p = 0.01). CONCLUSION: Sonothrombolysis in patients with STEMI resulted in improved wall motion and ventricular perfusion scores over time.

FUNDAMENTO: Demonstrou-se recentemente que a aplicação de ultrassom de alta energia com microbolhas, técnica conhecida como sonotrombólise, causa a dissolução de trombos intravasculares e aumenta a taxa de recanalização angiográfica no infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAM-CSST). OBJETIVO: Avaliar o efeito da sonotrombólise nos índices de motilidade e perfusão miocárdicas em pacientes com IAM-CSST, utilizando a ecocardiografia com perfusão miocárdica em tempo real (EPMTR). MÉTODO: Uma centena de pacientes com IAM-CSST foram randomizados em dois grupos: Terapia (50 pacientes tratados com sonotrombólise e angioplastia coronária primária) e Controle (50 pacientes tratados com angioplastia coronária primária). Os pacientes realizaram EPMTR para analisar a fração de ejeção do ventrículo esquerdo (FEVE), o índice de escore de motilidade segmentar (IEMS) e o número de segmentos com defeito de perfusão miocárdica, 72 horas após o IAM-CSST e com 6 meses de acompanhamento. Foi considerado significativo p < 0,05. RESULTADOS: Pacientes tratados com sonotrombólise apresentaram FEVE mais alta que o grupo Controle em 72 horas (50 ± 10% vs. 44 ± 10%; p = 0,006), e essa melhora foi mantida em seis meses (53 ± 10% vs. 48 ± 12%; p = 0,008). O IEMS foi similar nos grupos Terapia e Controle em 72 horas (1,62 ± 0,39 vs. 1,75 ± 0,40; p = 0,09), mas tornou-se menor no grupo Terapia em 6 meses (1,46 ± 0,36 vs. 1,64 ± 0,44; p = 0,02). O número de segmentos com defeito de perfusão não foi diferente entre os grupos em 72 horas (5,92 ± 3,47 vs. 6,94 ± 3,39; p = 0,15), mas ficou menor no grupo Terapia em 6 meses (4,64 ± 3,31 vs. 6,57 ± 4,29; p = 0,01). CONCLUSÃO: A sonotrombólise em pacientes com IAM-CSST resulta na melhora dos índices de motilidade e perfusão ventricular ao longo do tempo.

Desempenho Diagnóstico da Angiotomografia Computadorizada e da Avaliação Seriada de Troponina Cardíaca Sensível em Pacientes com Dor Torácica e Risco Intermediário para Eventos Cardiovasculares / Diagnostic Performance of Coronary Tomography Angiography and Serial Measurements of Sensitive Cardiac Troponin in Patients With Chest Pain and Intermediate Risk for Cardiovascular Events

Resumo Fundamento A angiotomografia coronária (ATC) tem sido usada para avaliação de dor torácica principalmente em pacientes de baixo risco, e poucos dados existem com pacientes em risco intermediário. Objetivo Avaliar o desempenho de medidas seriadas de troponinas sensíveis e de ATC em pacientes de risco intermediário. Métodos Um total de 100 pacientes com dor torácica, TIMI score 3 ou 4 e troponina negativa foram prospectivamente incluídos. Todos os pacientes foram submetidos à ATC, e aqueles com obstruções ≥ 50% foram encaminhados à cineangiocoronariografia. Pacientes com lesões < 50% recebiam alta hospitalar, receberam alta e foram contatados 30 dias depois por telefonema para avaliação dos desfechos clínicos. Os desfechos foram hospitalização, morte, e infarto agudo do miocárdio em 30 dias. A comparação entre os métodos foi realizada pelo teste de concordância kappa. O desempenho das medidas de troponina e da ATC na detecção de lesões coronárias significativas e desfechos clínicos foi calculado. Os resultados foram considerados estatisticamente significativos quando p <0,05. Resultados Estenose coronária ≥ 50% na ATC foi encontrada em 38% dos pacientes e lesões coronárias significativas na angiografia coronária foram encontradas em 31 pacientes. Dois eventos clínicos foram observados. A análise de concordância Kappa mostrou baixa concordância entre as medidas de troponina e ATC na detecção de lesões coronárias significativas (kappa = 0,022, p = 0,78). O desempenho da ATC para detectar lesões coronárias significativas na angiografia coronária ou para prever eventos clínicos em 30 dias foi melhor que as medidas de troponina sensível (acurácia de 91% versus 60%). Conclusão ATC teve melhor desempenho que as medidas seriadas de troponina na detecção de doença coronariana significativa em pacientes com dor torácica e risco intermediário para eventos cardiovasculares.

Abstract Background Coronary tomography angiography (CTA) has been mainly used for chest pain evaluation in low-risk patients, and few data exist regarding patients at intermediate risk. Objective To evaluate the performance of serial measures of sensitive troponin and CTA in intermediate-risk patients. Methods A total of 100 patients with chest pain, TIMI risk scores of 3 or 4, and negative troponin were prospectively included. All patients underwent CTA and those with coronary stenosis ≥ 50% were referred to invasive coronary angiography. Patients with coronary lesions <50% were discharged and contacted 30 days later by a telephone call to assess clinical outcomes. Outcomes were hospitalization, death, and myocardial infarction at 30 days. The comparison between methods was performed by Kappa agreement test. The performance of troponin measures and CTA for detecting significant coronary lesions and clinical outcomes was calculated. Results were considered statistically significant when p < 0.05. Results Coronary stenosis ≥ 50% on CTA was found in 38% of patients and significant coronary lesions on coronary angiography were found in 31 patients. Two clinical events were observed. Kappa agreement analysis showed low agreement between troponin measures and CTA in the detection of significant coronary lesions (kappa = 0.022, p = 0.78). The performance of CTA for detecting significant coronary lesions on coronary angiography or for predicting clinical events at 30 days was better than sensitive troponin measures (accuracy of 91% versus 60%). Conclusion CTA performed better than sensitive troponin measures in the detection of significant coronary disease in patients with chest pain and intermediate risk for cardiovascular events.

A Sonotrombólise Promove Melhora dos Índices de Motilidade e Perfusão do Ventrículo Esquerdo após o Infarto Agudo do Miocárdio / Sonothrombolysis Promotes Improvement in Left Ventricular Wall Motion and Perfusion Scores after Acute Myocardial Infarction

Resumo Fundamento Demonstrou-se recentemente que a aplicação de ultrassom de alta energia com microbolhas, técnica conhecida como sonotrombólise, causa a dissolução de trombos intravasculares e aumenta a taxa de recanalização angiográfica no infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAM-CSST). Objetivo Avaliar o efeito da sonotrombólise nos índices de motilidade e perfusão miocárdicas em pacientes com IAM-CSST, utilizando a ecocardiografia com perfusão miocárdica em tempo real (EPMTR). Método Uma centena de pacientes com IAM-CSST foram randomizados em dois grupos: Terapia (50 pacientes tratados com sonotrombólise e angioplastia coronária primária) e Controle (50 pacientes tratados com angioplastia coronária primária). Os pacientes realizaram EPMTR para analisar a fração de ejeção do ventrículo esquerdo (FEVE), o índice de escore de motilidade segmentar (IEMS) e o número de segmentos com defeito de perfusão miocárdica, 72 horas após o IAM-CSST e com 6 meses de acompanhamento. Foi considerado significativo p < 0,05. Resultados Pacientes tratados com sonotrombólise apresentaram FEVE mais alta que o grupo Controle em 72 horas (50 ± 10% vs. 44 ± 10%; p = 0,006), e essa melhora foi mantida em seis meses (53 ± 10% vs. 48 ± 12%; p = 0,008). O IEMS foi similar nos grupos Terapia e Controle em 72 horas (1,62 ± 0,39 vs. 1,75 ± 0,40; p = 0,09), mas tornou-se menor no grupo Terapia em 6 meses (1,46 ± 0,36 vs. 1,64 ± 0,44; p = 0,02). O número de segmentos com defeito de perfusão não foi diferente entre os grupos em 72 horas (5,92 ± 3,47 vs. 6,94 ± 3,39; p = 0,15), mas ficou menor no grupo Terapia em 6 meses (4,64 ± 3,31 vs. 6,57 ± 4,29; p = 0,01). Conclusão A sonotrombólise em pacientes com IAM-CSST resulta na melhora dos índices de motilidade e perfusão ventricular ao longo do tempo.

Abstract Background It has recently been demonstrated that the application of high-energy ultrasound and microbubbles, in a technique known as sonothrombolysis, dissolves intravascular thrombi and increases the angiographic recanalization rate in patients with ST-segment-elevation myocardial infarction (STEMI). Objective To evaluate the effects of sonothrombolysis on left ventricular wall motion and myocardial perfusion in patients with STEMI, using real-time myocardial perfusion echocardiography (RTMPE). Methods One hundred patients with STEMI were randomized into the following 2 groups: therapy (50 patients treated with sonothrombolysis and primary coronary angioplasty) and control (50 patients treated with primary coronary angioplasty). The patients underwent RTMPE for analysis of left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and number of segments with myocardial perfusion defects 72 hours after STEMI and at 6 months of follow-up. P < 0.05 was considered statistically significant. Results Patients treated with sonothrombolysis had higher LVEF than the control group at 72 hours (50% ± 10% versus 44% ± 10%; p = 0.006), and this difference was maintained at 6 months of follow-up (53% ± 10% versus 48% ± 12%; p = 0.008). The WMSI was similar in the therapy and control groups at 72 hours (1.62 ± 0.39 versus 1.75 ± 0.40; p = 0.09), but it was lower in the therapy group at 6 months (1.46 ± 0.36 versus 1.64 ± 0.44; p = 0.02). The number of segments with perfusion defects on RTMPE was similar in therapy and control group at 72 hours (5.92 ± 3.47 versus 6.94 ± 3.39; p = 0.15), but it was lower in the therapy group at 6 months (4.64 ± 3.31 versus 6.57 ± 4.29; p = 0.01). Conclusion Sonothrombolysis in patients with STEMI resulted in improved wall motion and ventricular perfusion scores over time.

Diagnostic Performance of Coronary Tomography Angiography and Serial Measurements of Sensitive Cardiac Troponin in Patients With Chest Pain and Intermediate Risk for Cardiovascular Events. / Desempenho Diagnóstico da Angiotomografia Computadorizada e da Avaliação Seriada de Troponina Cardíaca Sensível em Pacientes com Dor Torácica e Risco Intermediário para Eventos Cardiovasculares.

BACKGROUND: Coronary tomography angiography (CTA) has been mainly used for chest pain evaluation in low-risk patients, and few data exist regarding patients at intermediate risk. OBJECTIVE: To evaluate the performance of serial measures of sensitive troponin and CTA in intermediate-risk patients. METHODS: A total of 100 patients with chest pain, TIMI risk scores of 3 or 4, and negative troponin were prospectively included. All patients underwent CTA and those with coronary stenosis ≥ 50% were referred to invasive coronary angiography. Patients with coronary lesions <50% were discharged and contacted 30 days later by a telephone call to assess clinical outcomes. Outcomes were hospitalization, death, and myocardial infarction at 30 days. The comparison between methods was performed by Kappa agreement test. The performance of troponin measures and CTA for detecting significant coronary lesions and clinical outcomes was calculated. Results were considered statistically significant when p < 0.05. RESULTS: Coronary stenosis ≥ 50% on CTA was found in 38% of patients and significant coronary lesions on coronary angiography were found in 31 patients. Two clinical events were observed. Kappa agreement analysis showed low agreement between troponin measures and CTA in the detection of significant coronary lesions (kappa = 0.022, p = 0.78). The performance of CTA for detecting significant coronary lesions on coronary angiography or for predicting clinical events at 30 days was better than sensitive troponin measures (accuracy of 91% versus 60%). CONCLUSION: CTA performed better than sensitive troponin measures in the detection of significant coronary disease in patients with chest pain and intermediate risk for cardiovascular events.

FUNDAMENTO: A angiotomografia coronária (ATC) tem sido usada para avaliação de dor torácica principalmente em pacientes de baixo risco, e poucos dados existem com pacientes em risco intermediário. OBJETIVO: Avaliar o desempenho de medidas seriadas de troponinas sensíveis e de ATC em pacientes de risco intermediário. MÉTODOS: Um total de 100 pacientes com dor torácica, TIMI score 3 ou 4 e troponina negativa foram prospectivamente incluídos. Todos os pacientes foram submetidos à ATC, e aqueles com obstruções ≥ 50% foram encaminhados à cineangiocoronariografia. Pacientes com lesões < 50% recebiam alta hospitalar, receberam alta e foram contatados 30 dias depois por telefonema para avaliação dos desfechos clínicos. Os desfechos foram hospitalização, morte, e infarto agudo do miocárdio em 30 dias. A comparação entre os métodos foi realizada pelo teste de concordância kappa. O desempenho das medidas de troponina e da ATC na detecção de lesões coronárias significativas e desfechos clínicos foi calculado. Os resultados foram considerados estatisticamente significativos quando p <0,05. RESULTADOS: Estenose coronária ≥ 50% na ATC foi encontrada em 38% dos pacientes e lesões coronárias significativas na angiografia coronária foram encontradas em 31 pacientes. Dois eventos clínicos foram observados. A análise de concordância Kappa mostrou baixa concordância entre as medidas de troponina e ATC na detecção de lesões coronárias significativas (kappa = 0,022, p = 0,78). O desempenho da ATC para detectar lesões coronárias significativas na angiografia coronária ou para prever eventos clínicos em 30 dias foi melhor que as medidas de troponina sensível (acurácia de 91% versus 60%). CONCLUSÃO: ATC teve melhor desempenho que as medidas seriadas de troponina na detecção de doença coronariana significativa em pacientes com dor torácica e risco intermediário para eventos cardiovasculares.