Patients with ST-elevation myocardial infarction (STEMI) and late arrival (>12 h) after symptom onset, are at high risk for mortality and heart failure and represent a challenge for management. We ...aimed to define patient characteristics, management, and outcome of late-arrival STEMI in Israel over the last 20 years.
We analyzed data of late-arrival STEMI (12–48 h and > 48 h) from the biennial acute coronary syndrome Israeli Surveys (ACSIS), as well as time-dependent changes early (2000–2010) Vs. late (2013–2021) period.
Data regarding time from symptom onset to hospital arrival was available in 6,466 STEMI patients. Of these, 9.6 % arrived 12–48 h and 3 % >48 h from symptom onset. Late-arrival patients were more likely to be older women with diabetes and high GRACE score and less likely to have prior myocardial infarction.
In recent years, 95 % of patients arriving 12–48 h and 96 % of those arriving > 48 h had coronary angiography, as opposed to 75 % and 77 % in the early years (p = 0.007). Percutaneous coronary intervention (PCI) increased from 60 % and 55 % respectively to 85 % (p ≤ 0.001).
TIMI-3 flow after primary PCI was 89–92 %, irrespective of arrival time. Late arrival patients (12–48 h but not > 48 h) who had PCI had better adjusted 1-year survival, HR 0.49 (95 %CI 0.29–0.82), p = 0.01.
Late-arrival STEMI patients have higher risk characteristics. Most late-arrival patients undergo coronary angiography and PCI and have TIMI-3 flow after primary PCI. In patients arriving 12–48 h after symptom onset PCI is associated with better survival.
Angiographic revascularization grading after intra-arterial stroke therapy is limited by poor standardization, making it unclear which scale is optimal for predicting outcome. Using recently ...standardized criteria, we sought to compare the prognostic performance of 2 commonly used reperfusion scales.
Inclusion criteria for this multicenter retrospective study were acute ischemic stroke attributable to middle cerebral artery M1 occlusion, intra-arterial therapy, and 90-day modified Rankin scale score. Post-intra-arterial therapy reperfusion was graded using the Thrombolysis in Myocardial Infarction (TIMI) and Modified Thrombolysis in Cerebral Infarction (mTICI) scales. The scales were compared for prediction of clinical outcome using receiver-operating characteristic analysis.
Of 308 patients, mean age was 65 years, and median National Institutes of Health Stroke Scale score was 17. The mean time from stroke onset to groin puncture was 305 minutes. There was no difference in the time to treatment between patients grouped by final TIMI (ie, 0 versus 1 versus 2 versus 3) or mTICI grades (ie, 0 versus 1 versus 2a versus 2b versus 3). Good outcome (modified Rankin scale, 0-2) was achieved in 32.5% of patients, and mortality rate was 25.3% at 90 days. There was a 6.3% rate of parenchymal hematoma type 2. In receiver-operating characteristic analysis, mTICI was superior to TIMI for predicting 90-day modified Rankin scale 0 to 2 (c-statistic: 0.74 versus 0.68; P<0.0001). The optimal threshold for identifying a good outcome was mTICI 2b to 3 (sensitivity 78.0%; specificity 66.1%).
mTICI is superior to TIMI for predicting clinical outcome after intra-arterial therapy. mTICI 2b to 3 is the optimal biomarker for procedural success.
Objective: Disposition in acute coronary syndrome (ACS) is pivotal in an emergency department (ED). HEART score is a recent scoring system for finding primary endpoints in undetermined ACS. This ...study aimed at evaluating the predictive value of HEART score in ACS outcome and disposition. Methods: In this prospective study, all patients with chest pain presentation compatible with our inclusion criteria referring to ED were enrolled during one year. Demographic data, triage level, hospital length of stay, admission ward, coronary angiography result, HEART score, thrombolysis in myocardial infarction (TIMI) score, 1-month primary ACS endpoints and major adverse cardiac events (MACE) were evaluated. Results: In our studied population (200 cases), 49 patients (24.5%) had at least one score for MACE. Comparing the prognostic values of TIMI vs HEART score in MACE revealed that the HEART had a larger AUC. The best cut-off point of HEART score in MACE prediction was calculated to be ≥5. There was a statistically significant relation between HEART score and hospital length of stay. The higher the HEART score, the more probability of patients being admitted to either hospital cardiac ward or coronary care unit (CCU). There was a significant relationship between the triage level and HEART score. Patients with higher HEART score had more acuity (lower triage level 1 or 2). Conclusion: HEART predicted MACE better than TIMI in low risk ACS. Patients with higher HEART score were more admitted to the hospital with longer hospital stay and patients with lower HEART score had higher triage level with less acuity.
Restoration of myocardial blood flow and perfusion during percutaneous coronary intervention (PCI) measured using Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and perfusion grade ...(TMPG) is associated with improved outcomes in acute coronary syndrome (ACS). Associations between TFG/TMPG and changes in biomarkers reflecting myocardial damage/dysfunction and inflammation is unknown.
Among 2606 patients included, TFG was evaluated in 2198 and TMPG in 1874 with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment ACS (NSTE-ACS). Biomarkers reflecting myocardial necrosis troponin T (TnT), myocardial dysfunction N-terminal prohormone brain natriuretic peptide (NT-proBNP), inflammation interleukin-6 (IL-6) and C-reactive protein (CRP), and oxidative stress/ageing/inflammation growth differentiation factor-15 (GDF-15) were measured at baseline, discharge, and 1- and 6-month post-randomization. Associations between TFG/TMPG and changes in biomarker levels were evaluated using the Mann-Whitney-Wilcoxon signed test. In total, 1423 (54.6%) patients had STEMI and 1183 (45.4%) NSTE-ACS. Complete reperfusion after PCI with TFG = 3 was achieved in 1110 (85.3%) with STEMI and in 793 (88.5%) with NSTE-ACS. Normal myocardial perfusion with TMPG = 3 was achieved in 475 (41.6%) with STEMI and in 396 (54.0%) with NSTE-ACS. Levels of TnT, NT-proBNP, IL-6, CRP, and GDF-15 were substantially lower at discharge in patients with complete vs. incomplete TFG and STEMI (P < 0.01). This pattern was not observed for patients with NSTE-ACS. Patients with normal vs. abnormal TMPG and NSTE-ACS had lower levels of NT-proBNP at discharge (P = 0.01).
Successful restoration of epicardial blood flow in STEMI was associated with less myocardial necrosis/dysfunction and inflammation. Attainment of normal myocardial perfusion was associated with less myocardial dysfunction in NSTE-ACS.
We aimed to evaluate the association between ocular microvasculature (vascular density) on optical coherence tomography-angiography (OCT-A) and the cardiovascular risk profile of patients ...hospitalized for non-ST-elevation myocardial infarction (NSTEMI) patients.
Patients admitted to the intensive care unit with the diagnosis of NSTEMI and undergoing coronary angiography were divided into 3 groups as low, intermediate, and high risk according to the SYNTAX score. OCT-A imaging was performed in all three groups. Right-left selective coronary angiography images of all patients were analyzed. The SYNTAX and TIMI risk scores of all patients were calculated.
This study included opthalmological examination of 114 NSTEMI patients. NSTEMI patients with high SYNTAX risk scores had significantly lower deep parafoveal vessel density (DPD) than patients with low-intermediate SYNTAX risk scores (p < 0.001). ROC curve analysis found that a DPD threshold below 51.65 % was moderately associated with high SYNTAX risk scores in patients with NSTEMI. In addition, NSTEMI patients with high TIMI risk scores had significantly lower DPD than patients with low-intermediate TIMI risk scores (p < 0.001).
OCT-A may be a non-invasive useful tool to assess the cardiovascular risk profile of NSTEMI patients with a high SYNTAX and TIMI score.
To summarize the four recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials: Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58), CANagliflozin CardioVascular Assessment Study ...(CANVAS) Program, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), and explore the potential determinants for their cardiovascular, renal, and safety outcomes.
The composite renal outcome event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 3.7, 7.0, 47%; 5.5, 9.0, 40%; 6.3, 11.5, 46%; 43.2, 61.2, 30% for DECLARE-TIMI 58, CANVAS, EMPA-REG OUTCOME, and CREDENCE, respectively (event definitions varied across trials). The major adverse cardiovascular (CV) event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 22.6, 24.2, 7%; 26.9, 31.5, 14%; 37.4, 43.9, 14%; 38.7, 48.7, 20% for DECLARE-TIMI 58, CANVAS, EMPA-REG OUTCOME, and CREDENCE, respectively. DECLARE-TIMI 58 had the fewest cardiorenal events and CREDENCE the most. These differences were presumably due to varying inclusion criteria resulting in DECLARE-TIMI 58 having the best baseline renal filtration function and CREDENCE the worst (mean estimated glomerular filtration rate 85.2, 76.5, 74, 56.2 mL/min/1.73 m
for DECLARE-TIMI 58, CANVAS, EMPA-REG OUTCOME, and CREDENCE, respectively). Additionally, CREDENCE had considerably higher rates of albuminuria (median urinary albumin-creatinine ratios (UACR) were 927, 12.3, and 13.1 mg/g for CREDENCE, CANVAS, and DECLARE-TIMI 58, respectively; EMPA-REG OUTCOME had 59.4% UACR < 30, 28.6% UACR > 30-300, 11.0% UACR > 300 mg/g).
Dapagliflozin, empagliflozin, and canagliflozin have internally and externally consistent and biologically plausible class effects on cardiorenal outcomes. Baseline renal filtration function and degree of albuminuria are the most significant indicators of risk for both CV and renal events. Thus, these two factors also anticipate the greatest clinical benefit for SGLT2i.
Abstract Purpose Although recent reports suggest an association between saxagliptin and an increased risk of admissions for heart failure, it is not clear whether dipeptidyl peptidase IV (DPP-IV) ...inhibition contributes to heart failure in high-risk patients. The purpose of this research is to understand heart failure risk among high-risk patients with type 2 diabetes. Methods This is a systematic review of data published in full papers and abstract form using the terms DPP-IV inhibitors and heart failure published since October 2013. Data from insurance and hospital databases were combined with those from multiple published trials, including the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial; Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care (EXAMINE), and Vildagliptin in Ventricular Dysfunction Diabetes (VIVIDD) trial as well as pooled analyses of linagliptin and saxagliptin placebo-controlled trials to examine heart failure among patients represented in those datasets. Findings A meta-analysis of the 9 datasets showed an increase in heart failure with dipeptidyl peptidase IV inhibitors of 15% ( P = 0.017). There was no statistical heterogeneity, nor was there a statistical difference between cohort studies and randomized, controlled trials ( P = 0.3), even though cohort studies alone were not significant (relative risk: 1.1; P = 0.32). Removing SAVOR-TIMI 53 data produced an insignificant increase in heart failure of 12% ( P = 0.09) in the rest of the studies. In the randomized, controlled trials, the increased risk was 24% ( P = 0.002). There was no statistical difference between those studies with and without baseline cardiovascular disease ( P = 0.58), although the cardiovascular disease studies were borderline significant ( P = 0.06). There was no publication bias. Implications There are data from studies using sitagliptin, saxagliptin, and alogliptin showing that these agents may increase the risk of hospitalization for heart failure. More data are required for a definitive conclusion.
The use of intravenous antiplatelet therapy during primary percutaneous coronary intervention (PPCI) is not fully standardized. The aim is to evaluate the effectiveness and safety of periprocedural ...intravenous administration of cangrelor or tirofiban in a contemporary ST-segment elevation myocardial infarction (STEMI) population undergoing PPCI. This was a multicenter prospective cohort study including consecutive STEMI patients who received cangrelor or tirofiban during PPCI at seven Italian centers. The primary effectiveness measure was the angiographic evidence of thrombolysis in myocardial infarction (TIMI) flow < 3 after PPCI. The primary safety outcome was the in-hospital occurrence of BARC (Bleeding Academic Research Consortium) 2–5 bleedings. The study included 627 patients (median age 63 years, 79% males): 312 received cangrelor, 315 tirofiban. The percentage of history of bleeding, pulmonary edema and cardiogenic shock at admission was comparable between groups. Patients receiving cangrelor had lower ischemia time compared to tirofiban. TIMI flow before PPCI and TIMI thrombus grade were comparable between groups. At propensity score-weighted regression analysis, the risk of TIMI flow < 3 was significantly lower in patients treated with cangrelor compared to tirofiban (adjusted OR: 0.40; 95% CI: 0.30–0.53). The risk of BARC 2–5 bleeding was comparable between groups (adjusted OR:1.35; 95% CI: 0.92–1.98). These results were consistent across multiple prespecified subgroups, including subjects stratified for different total ischemia time, with no statistical interaction. In this real-world multicenter STEMI population, the use of cangrelor was associated with improved myocardial perfusion assessed by coronary angiography after PPCI without increasing clinically-relevant bleedings compared to tirofiban.
Graphical abstract
Serial pharmacokinetic (PK) sampling in 1159 patients from TRITON‐TIMI 38 was undertaken. A multilinear regression model was used to quantitatively predict prasugrel's active metabolite (Pras‐AM) ...concentrations from its 2 downstream inactive metabolites. Population‐based methods were then applied to Pras‐AM concentration data to characterize the PK. The potential influence of body weight, body mass index, age, sex, renal function, diabetes, tobacco use, and other disease status on Bayesian estimates of Pras‐AM exposures was assessed. The PK of Pras‐AM was adequately described by a multicompartmental model and consistent with results from previous studies. The systemic exposure of prasugrel was not appreciably affected by body mass index, gender, diabetes, smoking, and renal impairment. Pras‐AM mean exposure in patients weighing <60 kg (4.1%) was 30% (90% confidence interval CI 1.16–1.45) higher than exposure in patients ≥60 kg. Mean Pras‐AM exposures for patients ≥75 years (10.5%) were 19% (90% CI: 1.11–1.28) higher compared with patients <75 years.
The involvement of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-2 (IGFBP-2) following acute coronary syndrome (ACS) is rarely studied in clinical practice. ...Therefore, we sought to evaluate the relationship between IGF-1 and IGFBP-2 concentrations at admission and risk stratification based on the Thrombolysis in Myocardial Infarction (TIMI) risk score in patients with ACS.
In all, 304 patients diagnosed with ACS were included in this study. Plasma IGF-1 and IGFBP-2 were measured using commercially available ELISA kits. The TIMI risk score was calculated and the study population was stratified into high (n = 65), medium (n = 138), and low (n = 101) risk groups. Levels of IGF-1 and IGFBP-2 were analyzed for their predictive ability of risk stratification based on the TIMI risk scores. Correlation analysis showed that IGF-1 levels were negatively correlated with TIMI risk levels (r = −0.144, p = 0.012), while IGFBP-2 levels were significantly and positively correlated with TIMI risk levels (r = 0.309, p < 0.001). In multivariate logistic regression analysis, IGF-1 (odds ratio OR: 0.995; 95% confidence interval CI: 0.990–1.000; p = 0.043) and IGFBP-2 (OR: 1.002; 95%CI: 1.001–1.003; p < 0.001) were independent predictors of high TIMI risk levels. In receiver operating characteristic curves, the area under the curve values for IGF-1 and IGFBP-2 in the prediction of high TIMI risk levels were 0.605 and 0.723, respectively.
IGF-1 and IGFBP-2 levels are excellent biomarkers for risk stratification in patients with ACS, which provides further guidance for clinicians to identify patients at high risk and to lower their risk.
•Plasma of IGF-1 was lower, while IGFBP-2 was higher in AMI than in UA group.•IGF-1 levels were negatively correlated with TIMI risk levels.•IGFBP-2 levels were significantly and positively correlated with TIMI risk levels.•IGF-1 and IGFBP-2 were independent predictors of high TIMI risk levels.