Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality across the world, warranting continuous research in this field. The elucidation of the atherogenesis ...mechanism is considered one of the most relevant scientific accomplishments of the last century. This has led to the clinical development of various novel therapeutic interventions for patients with or at risk of ASCVD, in which randomized clinical trials played a crucial role.The Thrombolysis in Myocardial Infarction (TIMI) Study Group was initially established to conduct a clinical trial studying thrombolysis for treatment of myocardial infarction. However, over the years, the TIMI Study Group has expanded their research interests to include antithrombotic therapy, lipid lowering, anti-diabetes, anti-obesity, and even heart failure. By leading large-scale, international, randomized, controlled trials of novel therapeutics, the TIMI Study Group has helped shape the very practice of cardiovascular medicine for over a quarter of a century, and decades of research continue to provide future promise for further advancement. Through a mutual goal to improve the care of ASCVD patients, the Japanese scientific community has become one of the important contributors to the TIMI Study Group’s clinical research.In this review article, the authors aim to summarize major research lead by the TIMI Study Group in the ASCVD field.
We recently described the CHA2DS2-VASc-HS score as a novel predictor of coronary artery disease (CAD) severity in stable CAD patients. We aimed to assess the accuracy of the CHA2DS2-VASc-HS score in ...the determination of CAD severity and complexity and its availability in the risk stratification of in-hospital major adverse cardiovascular events (MACE) in non-ST elevation acute coronary syndrome (NSTE-ACS) patients.
We prospectively analyzed the clinical and angiographic data of consecutive NSTE-ACS patients in our clinic. Patients were classified into three tertiles according to their SYNTAX score (SS): tertile 1 had an SS of 0-22; tertile 2 had an SS of 23-32; and tertile 3 had an SS of >32. There were no specific exclusion criteria except for previous coronary artery bypass grafting (CABG) because SS was validated for only native coronary arteries for this study. We used the following analyses: χ2 or Fisher's exact tests, one-way analysis of variance or Kruskal-Wallis tests, Pearson's or Spearman's tests, the receiver operating characteristics (ROC) curve analysis, the area under the curve (AUC) or C-statistic, and pairwise comparisons of the ROC curves.
A total of 252 patients were enrolled. There were 131 patients in tertile 1, 79 in tertile 2, and 42 in tertile 3. The number of diseased vessels was correlated with the Global Registry for Acute Coronary Events (GRACE) (p<0.001), Thrombolysis in Myocardial Infarction (TIMI) (p<0.001), and CHA2DS2-VASc-HS (p<0.001) scores. In the ROC curve analyses, the cut-off value of the CHA2DS2-VASc-HS score in the prediction of in-hospital MACE was >5 with a sensitivity of 69.6% and specificity of 90.3% (AUC: 0.804, 95%: CI 0.750-0.851, p<0.001). We also compared the diagnostic accuracy of the CHA2DS2-VASc-HS score with the TIMI and GRACE risk scores in the determination of the in-hospital MACE and found no differences.
The CHA2DS2-VASc-HS score was positively correlated with the severity and complexity of CAD. We also found that CHA2DS2-VASc-HS was comparable with other risk scores for the risk stratification of the in-hospital MACE of NSTE-ACS patients. Therefore, it may play an important role as a predictive model of NSTE-ACS patients in clinical practice.
We assessed the prognostic value of serum levels of endocan in patients with the acute coronary syndrome (ACS) through its correlation with the Thrombolysis in Myocardial Infarction (TIMI) risk score ...and compared the possible association with clinical outcomes. In this prospective cross-sectional study, we enrolled 320 patients with documented ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina (UA) who underwent diagnostic coronary angiography. Endocan was measured soon after admission in the emergency department. In-hospital death, heart failure, and recurrent infarction were considered major adverse cardiac events (MACEs). There was a significant positive correlation between endocan level and TIMI risk score and MACE. The optimal cutoff values of endocan to predict clinical end points were 3.45 ng/mL in patients with STEMI and 2.85 ng/mL in patients with UA/NSTEMI. Multivariate logistic regression analysis indicated that endocan independently correlated with MACE. Moreover, cardiac troponin I, creatine kinase-MB, and circulating endocan were found to be independently associated with MACE in patients with ACS. In conclusion, a high endocan level on hospital admission is an independent predictor of worse cardiovascular outcomes and higher TIMI risk score in patients with ACS.
Background Guidelines recommend that coronary slow flow phenomenon (CSFP), defined as corrected thrombolysis in myocardial infarction frame count (CTFC)
27, can diagnose coronary microvascular ...dysfunction (CMD) in patients with angina and nonobstructed coronary arteries. CSFP has also historically been regarded as a sign of coronary endothelial dysfunction (CED). We sought to validate the utility of CTFC, as a binary classifier of CSFP and as a continuous variable, to diagnose CMD and CED. Methods and Results Patients with angina and nonobstructed coronary arteries had simultaneous coronary pressure and flow velocity measured using a dual sensor-tipped guidewire during rest, adenosine-mediated hyperemia, and intracoronary acetylcholine infusion. CMD was defined as the inability to augment coronary blood flow in response to adenosine (coronary flow reserve <2.5) and CED in response to acetylcholine (acetylcholine flow reserve ≤1.5); 152 patients underwent assessment using adenosine, of whom 82 underwent further acetylcholine testing. Forty-six patients (30%) had CSFP, associated with lower flow velocity and higher microvascular resistance as compared with controls (16.5
6.9 versus 20.2
6.9 cm/s;
=0.001 and 6.26
1.83 versus 5.36
1.83 mm Hg/cm/s;
=0.009, respectively). However, as a diagnostic test, CSFP had poor sensitivity and specificity for both CMD (26.7% and 65.2%) and CED (21.1% and 56.0%). Furthermore, on receiver operating characteristics analyses, CTFC could not predict CMD or CED (area under the curve, 0.41 95% CI, 0.32%-0.50% and 0.36 95% CI, 0.23%-0.49%, respectively). Conclusions In patients with angina and nonobstructed coronary arteries, CSFP and CTFC are not diagnostic of CMD or CED. Guidelines supporting the use of CTFC in the diagnosis of CMD should be revisited.
Background: Accurate risk stratification in patient clinically presented as a case of Non-ST Elevation acute coronary syndrome (NSTE-ACS) is important to assess the prognosis as well as to estimate ...the possible adverse event especially in those patient who are at high risk. Of these scoring risk; Thrombolysis In Myocardial Infarction (TIMI) risk score have been well corroborated to predict the possible prognosis for patients with NSTE-ACS. However, their value in estimation the severity of coronary artery disease (CAD) has been less studied. Objective: To determine the role of TIMI score in prediction the severity of CAD and its extent by correlate the TIMI score with coronary angiography in patients have NSTE-ACS. Patients and Methods: A cross section study, conducted on 264 successive patients admitted with Non-ST Elevation acute coronary syndrome at Ibn-Albitar cardiac center, Baghdad, Iraq, from the 1st of October 2017 to the 1st of October 2018. Patients were rearranging into three groups according to the seven standard variables of TIMI score. The extent of CAD was examined on coronary angiography; a lesion defined significant if stenosis ≥70% in any artery of three major coronary arteries or ≥50% of left main coronary artery. Results: The total number of was 246 patients, mean age was 62.5±2.3 years. There were 67 (27.2%) of them belong to group 1 (low risk group), 142 (57.7%) of them belong to group 2 (intermediate risk group), and 37 (15.1%) of them belong to group 3 (high risk group). 54.1% of patients in group 3 had significant three-vessels coronary artery disease on comparing with 17.6% of group 2 patients and only 7.5% of group 1 patients had these lesions on coronary angiography (P-value <0.01). On the other hand, one-vessel coronary artery disease occurs more commonly and significant statistically (P-value <0.01) in group 2 (31.7%) than in patients in group 1 (26.9%) and group 3 (10.8%). Conclusion: High TIMI risk score patients were more probably to have significant multi-vessels coronary lesions in comparison with those with TIMI risk score in intermediate or low range which lead to help in stratify the risk and possibility of early intervention. Keywords: Coronary Angiography, Non-ST Elevation Acute Coronary Syndrome, Acute Coronary Syndrome risk stratification, TIMI score.
Objectives:
Patients presenting with chest pain or related symptoms suggestive of myocardial ischemia, without ST‐segment elevation (NSTE) on their presenting electrocardiograms, often present a ...diagnostic challenge in the emergency department (ED). Prompt and accurate risk stratification to identify those patients with NSTE chest pain who are at highest risk for adverse events is essential, however, to optimal management. Although validated and used frequently in patients already enrolled in acute coronary syndrome trials, the Thrombolysis in Myocardial Infarction (TIMI) risk score never has been examined for its value in risk stratification in an all‐comers, non–trial‐based ED chest pain population.
Methods:
An analysis of an ED‐based prospective observational cohort study was conducted in 3,929 adult patients presenting with chest pain syndrome and warranting evaluation with an electrocardiogram. These patients had TIMI risk scores determined at ED presentation. The main outcome was the composite of death, acute myocardial infarction (MI), and revascularization within 30 days.
Results:
The TIMI risk score at ED presentation successfully risk‐stratified this unselected cohort of chest pain patients with respect to 30‐day adverse outcome, with a range from 2.1%, with a score of 0, to 100%, with a score of 7. The highest correlation of an individual TIMI risk indicator to adverse outcome was for elevated cardiac biomarker at admission. Overall, the score had similar performance characteristics to that seen when applied to other databases of patients enrolled in clinical trials and registries using a 14‐day end point.
Conclusions:
The TIMI risk score may be a useful tool for risk stratification of ED patients with chest pain syndrome.
The MAPH (mean platelet volume, age, total protein and hematocrit) score is a newly developed simple scoring system for patients with STEMI that has been associated with satisfactory predictive ...values to determine thrombus burden in STEMI patients. Therefore, the aim of our study was to determine the relationship between the MAPH risk score and TIMI flow in patients with STEMI.The study included 260 patients who underwent primary percutaneous coronary intervention between December 2019 to July 2022, and had TIMI 0 flow in the responsible coronary artery due to STEMI. According to the TIMI flow score after stent implantation, the patients were classified into either the no-reflow group (n = 59) or the normal flow group (n = 201). In order to calculate the MAPH score, ROC analysis was performed to find the cutoff point for each component of the MAPH score. MAPH scores were calculated (MPV + Age + Protein + Hematocrit) for both groups. Our study was a retrospective, observational study.In the multivariable regression analysis, the MAPH score (OR: 0.567; 95%CI: 0.330-0.973, P = 0.04) and glycoprotein IIb/IIIa inhibitors (OR: 0.249; 95%CI: 0.129-0.483, P < 0.001) were parameters found to be independent predictors of TIMI flow. An MAPH score value > 2.5 predicted the presence of low TIMI coronary flow in patients with STEMI, with 78% specificity and 45% sensitivity (ROC area under curve: 0.691, 95% CI: 0.617-0.766, P < 0.001).The MAPH risk score is simple, inexpensive, and quick to calculate. A high MAPH score may be an indicator of coronary no-reflow in patients with STEMI.
Background: Accurate risk stratification in patient clinically presented as a case of Non-ST Elevation acute coronary syndrome (NSTE-ACS) is important to assess the prognosis as well as to estimate ...the possible adverse event especially in those patient who are at high risk. Of these scoring risk; Thrombolysis In Myocardial Infarction (TIMI) risk score have been well corroborated to predict the possible prognosis for patients with NSTE-ACS. However, their value in estimation the severity of coronary artery disease (CAD) has been less studied. Objective: To determine the role of TIMI score in prediction the severity of CAD and its extent by correlate the TIMI score with coronary angiography in patients have NSTE-ACS. Patients and Methods: A cross section study, conducted on 264 successive patients admitted with Non-ST Elevation acute coronary syndrome at Ibn-Albitar cardiac center, Baghdad, Iraq, from the 1st of October 2017 to the 1st of October 2018. Patients were rearranging into three groups according to the seven standard variables of TIMI score. The extent of CAD was examined on coronary angiography; a lesion defined significant if stenosis ≥70% in any artery of three major coronary arteries or ≥50% of left main coronary artery. Results: The total number of was 246 patients, mean age was 62.5±2.3 years. There were 67 (27.2%) of them belong to group 1 (low risk group), 142 (57.7%) of them belong to group 2 (intermediate risk group), and 37 (15.1%) of them belong to group 3 (high risk group). 54.1% of patients in group 3 had significant three-vessels coronary artery disease on comparing with 17.6% of group 2 patients and only 7.5% of group 1 patients had these lesions on coronary angiography (P-value <0.01). On the other hand, one-vessel coronary artery disease occurs more commonly and significant statistically (P-value <0.01) in group 2 (31.7%) than in patients in group 1 (26.9%) and group 3 (10.8%). Conclusion: High TIMI risk score patients were more probably to have significant multi-vessels coronary lesions in comparison with those with TIMI risk score in intermediate or low range which lead to help in stratify the risk and possibility of early intervention.
Objectives
Our primary objective was to describe the risk of major adverse cardiac events (MACE) at 1, 6, and 12 months after a negative coronary computed tomography angiogram (cCTA), ...electrocardiogram (ECG) stress test, stress echocardiography, and myocardial perfusion scintigraphy (MPS) in low‐ to intermediate‐risk patients.
Methods
Initially, 952 articles were identified for screening, 81 met criteria for full‐text review, and once risk of bias was assessed, 33 articles were included in this meta‐analysis. We utilized a random‐effects model to assess pooled MACE event proportion for patients undergoing evaluation of acute coronary syndrome (ACS) when risk stratified to a low‐ to intermediate‐risk category after undergoing standard testing. Heterogeneity analysis was performed using Cochrane's Q‐test and I2 statistic.
Results
Twenty‐one studies evaluated follow‐up at 1 month with cCTA having a 0.09% (95% confidence interval CI = 0.03% to 0.26%) pooled MACE compared to 0.23% (95% CI = 0.01% to 5.8%) of the exercise stress testing (p = 1). MPS and cCTA had an overall event rate of 0.15% (95% CI = 0.06% to 0.41%) at 6 months (I2 = 0%). At 12 months, a subgroup analysis found a pooled cCTA MACE of 0.16% (95% CI = 0.04% to 0.65%) compared to 1.68% (95% CI = 0.01% to 2.6%) for stress echocardiography with low within‐group heterogeneity (I2 = 0%). Subgroup analysis of cCTA with no disease versus nonobstructive disease (<50% stenosis) did not find statistical difference in the MACE at both 1 month (0.17% 95% CI = 0.04% to 0.67% vs. 0.06% 95% CI = 0.01% to 0.34%) and 12 months (0.44% 95% CI = 0.09% to 2.2% vs. 0.54% 95% CI = 0.19% to 1.5%).
Conclusions
Patients presenting with chest pain who have a coronary CTA showing < 50% stenosis, negative ECG stress test, stress echocardiography, or stress myocardial perfusion scan in the past 12 months can be discharged without any further risk stratification if their ECG and troponin are reassuring given low MACE.
Objectives The PLATO (Platelet Inhibition and Patient Outcomes) angiographic substudy sought to compare the efficacy of ticagrelor versus clopidogrel with respect to angiographic outcomes before and ...after PCI in the setting of acute coronary syndrome. Background Greater platelet inhibition has been associated with improved angiographic outcomes before and after percutaneous coronary intervention (PCI). Therefore, it was hypothesized that treatment with ticagrelor, which achieves more rapid, higher, and more consistent platelet inhibition, would be associated with improved angiographic outcomes when compared with those of clopidogrel treatment. Methods The angiographic cohort consists of 2,616 patients drawn from the 18,624-patient PLATO trial. Clopidogrel naïve or pre-treated patients were randomized to 180 mg of ticagrelor or 300 mg of clopidogrel (75 mg for clopidogrel pre-treated patients). PCI patients were administered, as per treatment group: 1) an additional 90 mg of ticagrelor if >24 h following the initial loading dose; or 2) an optional further 300 mg of clopidogrel or placebo (total 600 mg) prior to PCI. The substudy primary endpoint was the incidence of post-PCI TIMI (Thrombolysis In Myocardial Infarction) myocardial perfusion grade 3 (TMPG 3) among patients who received a study drug prior to PCI. Results In total, 21.3% of patients were pretreated with clopidogrel prior to randomization. There was a short time interval between randomization and PCI (median: 0.68 interquartile range (IQR): 0.30 to 2.21 h) among all patients. Post-PCI TMPG 3 was similar between the ticagrelor and clopidogrel groups (47.1% vs. 46.9%; p = 0.96). Likewise, the following pre-PCI outcomes were similar in the ticagrelor and clopidogrel groups, respectively: TMPG 3 (30.5% vs. 31.2%), TIMI flow grade 3 (37.1% vs. 39.3%), corrected TIMI frame count (median: 100 vs. 71 frames), TIMI thrombus grade 0 (24.1% vs. 27.6%), minimum lumen diameter (median: 0.3 IQR: 0.0 to 0.6 vs. 0.3 IQR: 0.0 to 0.6 mm) and percentage of diameter stenosis (median: 89 IQR: 78 to 100 vs. 89 IQR: 77 to 100). Conclusions Neither coronary flow nor myocardial perfusion, evaluated on coronary angiograms performed before or following PCI procedures within a few hours after the start of oral antiplatelet treatment in the setting of acute coronary syndromes, demonstrated a difference with ticagrelor versus clopidogrel. (A Comparison of Ticagrelor AZD6140 and Clopidogrel in Patients With Acute Coronary Syndrome PLATO; NCT00391872 )
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