BLT1 antagonist LSN2792613 reduces infarct size in a mouse model of myocardial ischaemia-reperfusion injury

AIMS: Restoration of coronary blood flow is crucial in the treatment of acute myocardial infarction. Reperfusion, however, induces ischaemia-reperfusion (IR) injury, which further deteriorates myocardial function. The innate immune system plays an important role in this process, mediating rapid influx of immune cells into the reperfused myocardium. Leukotriene B4 is an important leucocyte chemoattractant, performing its actions through binding to its specific receptor BLT1. We hypothesized that treatment with LSN2792613, a selective BLT1 antagonist, reduces infarct size (IS) in a mouse model of myocardial IR injury. METHODS AND RESULTS: Male C57Bl/6J mice were subjected to myocardial ischaemia for 30 min by surgical coronary artery ligation, followed by reperfusion. Mice received either LSN2792613 or vehicle, three times daily (orally) for up to 72 h after reperfusion. BLT1 inhibition with LSN2792613 reduced IS compared with vehicle treatment (26.9 ± 2.7 vs. 34.9 ± 2.2%, P = 0.030) at 24 h after reperfusion. The levels of IL-6 and keratinocyte chemoattractant were reduced in the infarcted tissue of LSN2792613-treated mice. Reduced apoptosis in LSN2792613-treated mice was suggested by increased levels of phosphorylated JNK and GSK3α/β, and confirmed by flow cytometric analysis showing less apoptotic and necrotic cardiomyocytes in the infarcted myocardium. Echocardiography at 4 weeks after myocardial IR showed a slightly higher ejection fraction and stroke volume in mice treated with LSN2792613 compared with vehicle-treated mice, whereas left ventricular volumes were comparable. CONCLUSION: Selective BLT1 inhibition with LSN2792613 reduces inflammation and apoptosis following IR, resulting in reduced IS, and therefore might be a promising strategy to prevent myocardial IR injury

Sex-Based Differences in the Performance of the HEART Score in Patients Presenting to the Emergency Department With Acute Chest Pain

BACKGROUND: Sex-based differences in clinical presentation, pathophysiology, and outcomes of patients with acute chest pain are increasingly being recognized, but are not implemented in guidelines and clinical prediction tools. We evaluated the performance of the HEART score in women versus men, because sex-based differences may exist among the algorithm's components: history, electrocardiogram, age, risk factors, and admission troponin level. METHODS AND RESULTS: The HEART score was retrospectively assessed in 831 women and 1084 men presenting to the emergency department with acute chest pain, assigning patients to the low-, intermediate-, or high-risk category for the occurrence of major adverse cardiac events (MACE) within 6 weeks. MACE, consisting of myocardial infarction, coronary revascularization, and all-cause death, also included events during index visit. Six-week MACE rates were 2 times lower in women than men (10.0% versus 20.8%; P<0.01). Despite similar discriminatory accuracy of the HEART score among women and men (c-statistic, 0.80 [0.75-0.84] versus 0.77 [0.74-0.81]; P=0.43), 6-week MACE rates were significantly lower in women than men across all HEART risk categories: 2.1% versus 6.5% (P<0.01) in the low-risk category, 12.7% versus 21.3% (P<0.01) in intermediate-risk category, and 53.1% versus 77.0% (P=0.02) in the high-risk category. The HEART score-adjusted risk ratio for men was 1.6 (1.3-2.0; P<0.01). CONCLUSIONS: The markedly higher 6-week MACE risk in men across all HEART risk categories should be taken into account when using the HEART score to guide clinical decision making; early discharge with a low-risk HEART score appears less safe for men than women with acute chest pain

Sex-Based Differences in the Performance of the HEART Score in Patients Presenting to the Emergency Department With Acute Chest Pain

BACKGROUND: Sex-based differences in clinical presentation, pathophysiology, and outcomes of patients with acute chest pain are increasingly being recognized, but are not implemented in guidelines and clinical prediction tools. We evaluated the performance of the HEART score in women versus men, because sex-based differences may exist among the algorithm's components: history, electrocardiogram, age, risk factors, and admission troponin level. METHODS AND RESULTS: The HEART score was retrospectively assessed in 831 women and 1084 men presenting to the emergency department with acute chest pain, assigning patients to the low-, intermediate-, or high-risk category for the occurrence of major adverse cardiac events (MACE) within 6 weeks. MACE, consisting of myocardial infarction, coronary revascularization, and all-cause death, also included events during index visit. Six-week MACE rates were 2 times lower in women than men (10.0% versus 20.8%; P<0.01). Despite similar discriminatory accuracy of the HEART score among women and men (c-statistic, 0.80 [0.75-0.84] versus 0.77 [0.74-0.81]; P=0.43), 6-week MACE rates were significantly lower in women than men across all HEART risk categories: 2.1% versus 6.5% (P<0.01) in the low-risk category, 12.7% versus 21.3% (P<0.01) in intermediate-risk category, and 53.1% versus 77.0% (P=0.02) in the high-risk category. The HEART score-adjusted risk ratio for men was 1.6 (1.3-2.0; P<0.01). CONCLUSIONS: The markedly higher 6-week MACE risk in men across all HEART risk categories should be taken into account when using the HEART score to guide clinical decision making; early discharge with a low-risk HEART score appears less safe for men than women with acute chest pain

Leucocyte expression of complement C5a receptors exacerbates infarct size after myocardial reperfusion injury

Aims Early reperfusion is mandatory for the treatment of acute myocardial infarction. This process, however, also induces additional loss of viable myocardium, called ischaemia-reperfusion (IR) injury. Complement activation plays an important role in IR injury, partly through binding of C5a to its major receptor (C5aR). We investigated the role of C5aR on infarct size and cardiac function in a model for myocardial IR injury

Predictors of major adverse cardiac events among patients with chest pain and low HEART score in the emergency department

10.1016/j.ijcard.2023.131573International Journal of Cardiology131573-13157

Ethnic differences in clinical outcome of patients presenting to the emergency department with chest pain

10.1177/2048872615623064EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE5732-4

HEART score performance in Asian and Caucasian patients presenting to the emergency department with suspected acute coronary syndrome

BACKGROUND: The HEART score is a simple and effective tool to predict short-term major adverse cardiovascular events in patients suspected of acute coronary syndrome. Patients are assigned to three risk categories using History, ECG, Age, Risk factors and Troponin (HEART). The purpose is early rule out and discharge is considered safe for patients in the low risk category. Its performance in patients of Asian ethnicity is unknown. We evaluated the performance of the HEART score in patients of Caucasian, Chinese, Indian and Malay ethnicity. METHODS: The HEART score was assessed retrospectively in 3456 patients presenting to the emergency department with suspected acute coronary syndrome (1791 Caucasians, 1059 Chinese, 344 Indians, 262 Malays), assigning them into three risk categories. RESULTS: The incidence of major adverse cardiovascular events within six weeks after presentation was similar between the ethnic groups. A smaller proportion of Caucasians was in the low risk category compared with Asians (Caucasians 35.8%, Chinese 43.5%, Indians 45.3%, Malays 44.7%, p<0.001). The negative predictive value of a low HEART score was comparable across the ethnic groups, but lower than previously reported (Caucasians 95.3%, Chinese 95.0%, Indians 96.2%, Malays 96.6%). Also the c-statistic for the HEART score was not significantly different between the groups. CONCLUSIONS: These results show that the overall performance of the HEART score is equal among Caucasian and Asian ethnic groups. The event rate in the low risk group, however, was higher than reported in previous studies, which queries the safety of early discharge of patients in the low risk category

HEART score performance in Asian and Caucasian patients presenting to the emergency department with suspected acute coronary syndrome

10.1177/2048872617700870EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE77591-60