Ticagrelor to Reduce Myocardial Injury in Patients With High-Risk Coronary Artery Plaque

ObjectivesThe goal of this study was to determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque.BackgroundHigh-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy.MethodsIn a randomized, double-blind, placebo-controlled trial, patients with multivessel coronary artery disease underwent coronary ¹⁸F-fluoride positron emission tomography/coronary computed tomography scanning and measurement of high-sensitivity cardiac troponin I. Patients were randomized (1:1) to receive ticagrelor 90 mg twice daily or matched placebo. The primary endpoint was troponin I concentration at 30 days in patients with increased coronary ¹⁸F-fluoride uptake.ResultsIn total, 202 patients were randomized to treatment, and 191 met the pre-specified criteria for inclusion in the primary analysis. In patients with increased coronary ¹⁸F-fluoride uptake (120 of 191), there was no evidence that ticagrelor had an effect on plasma troponin concentrations at 30 days (ratio of geometric means for ticagrelor vs. placebo: 1.11; 95% confidence interval: 0.90 to 1.36; p = 0.32). Over 1 year, ticagrelor had no effect on troponin concentrations in patients with increased coronary ¹⁸F-fluoride uptake (ratio of geometric means: 0.86; 95% confidence interval: 0.63 to 1.17; p = 0.33).ConclusionsDual antiplatelet therapy with ticagrelor did not reduce plasma troponin concentrations in patients with high-risk coronary plaque, suggesting that subclinical plaque thrombosis does not contribute to ongoing myocardial injury in this setting. (Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND]; NCT02110303)     

Myocardial infarction classification and its implications on measures of cardiovascular outcomes,quality, and racial/ethnic disparities

Heart disease continues to be the leading cause of death in the United States, with approximately 805 000 cumulative deaths from myocardial infarctions (MI) from 2005 to 2014. Gender and racial/ethnic disparities in MI diagnoses are becoming more evident in quality review audits. Although recent changes in diagnostic codes provided an improved framework, clinically distinguishing types of MI remains a challenge. MI misdiagnoses and health disparities contribute to adverse outcomes in cardiac medicine. We conducted a literature review of relevant biomedical sources related to the classification of MI and disparities in cardiovascular care and outcomes. From the studies analyzed, African Americans and women have higher rates of mortality from MI, are more probably to be younger and present with other comorbidities and are less probably to receive novel therapies with respect to type of MI. As high-sensitivity troponin assays are adopted in the United States, implementation should account for how race and sex differences have been demonstrated in the reference range and diagnostic threshold of the newer assays. More research is needed to assess how the complexity of health disparities contributes to adverse cardiovascular outcomes. Creating dedicated medical quality teams (physicians, nurses, clinical documentation improvement specialists, and medical coders) and incorporating a plan-do-check-adjust quality improvement model are strategies that could potentially help better define and diagnose MI, reduce financial burdens due to MI misdiagnoses, reduce cardiovascular-related health disparities, and ultimately improve and save lives.     

Heart-type fatty acid-binding protein: an overlooked cardiac biomarker

Abstract

Cardiac troponins (cTn) are currently the standard of care for the diagnosis of acute coronary syndromes (ACS) in patients presenting to the emergency department (ED) with chest pain (CP). However, their plasma kinetics necessitate a prolonged ED stay or overnight hospital admission, especially in those presenting early after CP onset. Moreover, ruling out ACS in low-risk patients requires prolonged ED observation or overnight hospital admission to allow serial measurements of c-Tn, adding cost. Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury with putative advantages over cTn. Being present in abundance in the myocellular cytoplasm, it is released rapidly (<1?h) after the onset of myocardial injury and could potentially play an important role in both earlier diagnosis of high-risk patients presenting early after CP onset, as well as in risk-stratifying low-risk patients rapidly. Like cTn, H-FABP also has a potential role as a prognostic marker in other conditions where the myocardial injury occurs, such as acute congestive heart failure (CHF) and acute pulmonary embolism (PE). This review provides an overview of the evidence examining the role of H-FABP in early diagnosis and risk stratification of patients with CP and in non-ACS conditions associated with myocardial injury.

• Key messages

• Heart-type fatty acid-binding protein is a biomarker that is elevated early in myocardial injury

• The routine use in the emergency department complements the use of troponins in ruling out acute coronary syndromes in patients presenting early with chest pain

• It also is useful in risk stratifying patients with other conditions such as heart failure and acute pulmonary embolism.

     

Clinical evaluation of Ortho Clinical Diagnostics high-sensitivity cardiac Troponin I assay in patients with symptoms suggestive of acute coronary syndrome

BackgroundAs more companies obtain regulatory approval for high-sensitivity cardiac troponin (hs-cTn) assays there is an urgent need for independent analytical and clinical evaluations. To this end, we have evaluated Ortho Clinical Diagnostics’ hs-cTnI assay and compared it to their contemporary cTnI-ES assay in emergency department (ED) patients with suspected acute coronary syndrome (ACS).MethodsThe study cohort consisted of ED patients (n = 906) with symptoms suggestive of ACS who had Ortho hs-cTnI and cTnI-ES results at presentation and 3 h (with calculated delta (0–3 h) defined as the absolute concentration difference between paired results). The primary composite outcome was 7-day myocardial infarction (MI) or cardiovascular death, with secondary analyses performed for 7-day MI and index-MI. Analytical imprecision testing (i.e., coefficient of variation; CV), receiver-operating characteristic (ROC) curve analyses with area under the curve (AUC), and diagnostic parameters (sensitivity/specificity/predictive values) were calculated.ResultsThe hs-cTnI assay had superior precision compared to the cTnI-ES assay below 5 ng/L in EDTA plasma (hs-cTnI CV ≤ 15% versus cTnI-ES CV ≥ 85%). The AUCs were higher for hs-cTnI as compared to cTnI-ES at 0 h (0.88 vs. 0.85), 3 h (0.94 vs. 0.92), and the delta (0–3 h) value (0.91 vs. 0.85) for the primary composite outcome (p < 0.05). At 3 h, the sensitivity/specificity for index-MI was ≥97%/≥82%, for 7-day MI was ≥89%/≥84%, and for the primary composite outcome was ≥90%/≥85% using the manufacturer’s sex-specific 99th-percentile cutoffs.ConclusionThe Ortho hs-cTnI assay has superior analytical and clinical performance over their contemporary cTnI-ES assay in evaluating ED patients with symptoms suggestive of ACS.     

脓毒症小鼠血清HMGB1与心肌损伤程度、炎症相关因子、BNP及cTnI水平的关系

目的 探讨血清高迁移率族蛋白B1(high mobility group box 1,HMGB1)在脓毒症小鼠心肌损伤中的作用及与心肌细胞炎症因子、血清B型钠尿肽(B-type natriuretic peptide,BNP)和肌钙蛋白(troponin,cTnI)的相关性。 方法 本研究选取6～8周龄、SPF级的昆明系小鼠60只,采用随机数字表法分为模型组、假手术组各30只,采用小鼠盲肠结扎穿孔法建立脓毒症小鼠模型,观察不同时间点小鼠血清HMGB1的水平变化,探讨其与心肌细胞凋亡率、心肌细胞炎症因子、血清B型钠尿肽(BNP)和肌钙蛋白(cTnI)的相关性。 结果 在0 h时刻,模型组和假手术组的血清HMGB1水平、心肌细胞凋亡率差异无统计学意义(P>0.05);在造模后12、24、48及72 h,模型组小鼠的血清HMGB1水平、心肌细胞凋亡率显著高于假手术组,差异均有统计学意义(P<0.05);在造模后48 h,模型组心肌组织中肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、IL-10、血清BNP、血清cTnI水平显著高于假手术组(P<0.05);在造模后48 h,模型组心肌组织中TNF-α、IL-6、IL-10、血清BNP、血清cTnI水平与血清HMGB1均呈显著正相关(P<0.05)。 结论 血清HMGB1在脓毒症小鼠中水平升高趋势明显,并且与小鼠心肌损伤具有密切的关系。