Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.

A Prediction Nomogram for No-Reflow in Acute Myocardial Infarction Patients after Primary Percutaneous Coronary Intervention.

Background: The coronary no-reflow (NR) phenomenon is an independent predictor of major adverse cardiac events (MACEs). This study aimed to establish a clinical and comprehensive nomogram for predicting NR in acute myocardial infarction (AMI) patients after primary percutaneous coronary intervention (pPCI). Methods: The multivariable logistic regression analysis was performed to determine the NR-related factors. A nomogram was established via several clinical and biochemical factors, and the performance was evaluated via discrimination, calibration, and clinical factors. Results: The study consisted of 3041 AMI patients after pPCI, including 2129 patients in the training set (70%) and 912 patients in the validation set (30%). The NR event was 238 in the training set and 87 in the validation set. The level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP), basophil count (BASO), neutrophil count (NEUBC), D-dimer, hemoglobin (Hb), and red blood cell distribution width (RDW.CV) in NR patients showed statistically significant differences. In the training set, the C-index was 0.712, 95% CI 0.677 to 0.748. In the validation set, the C-index was 0.663, 95% CI 0.604 to 0.722. Conclusions: A nomogram that may predict NR in AMI patients undergoing pPCI was established and validated. We hope this nomogram can be used for NR risk assessment and clinical decision-making and significantly prevent potentially impaired reperfusion associated with NR.

Early initiation of oral beta-blocker improves long-term survival in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention.

BACKGROUND: The optimal timing for the initiation of oral beta-blockers after acute myocardial infarction (MI) remains unclear within the context of current primary percutaneous coronary intervention (PCI) practice. METHODS: This retrospective cohort study included 412 consecutive patients admitted with a diagnosis of acute MI between January 2007 and August 2016 who underwent successful primary PCI and were given oral carvedilol during hospitalization. Early and late carvedilol groups were based on initiation within the first 24 h or after. Propensity score matching (1:1) incorporating 21 baseline characteristics yielded 47 matched pairs. Timing of carvedilol initiation was evaluated in relation to patient outcomes including time to all-cause mortality, using Kaplan-Meier estimates on the matched cohort and additional confirmation in multivariable regression analysis among the entire cohort. RESULTS: Median follow-up period was 828 days. All-cause death occurred in 14 patients (4.7%) and 18 patients (15.8%) of the early and late carvedilol groups. After propensity score matching, initiation of oral carvedilol within the first 24 h was associated with lower all-cause mortality (6.4% vs. 25.5%, hazard ratio 0.28, 95% confidence interval 0.06 - 0.89, p = 0.036), as well as lower in-hospital mortality (0 vs. 14.9%, p = 0.018). CONCLUSIONS: These results provide evidence that initiation of oral carvedilol within the first 24 h reduces the risk of long-term mortality, in acute MI patients who underwent primary PCI, supporting current guidelines recommendation.

The prognostic value of dynamic changes in SII for the patients with STEMI undergoing PPCI.

BACKGROUND: Predicting the prognosis of primary percutaneous coronary intervention(PPCI) in ST-segment elevation myocardial infarction (STEMI) patients in the perioperative period is of great clinical significance. The inflammatory response during the perioperative period is also an important factor. This study aimed to investigate the dynamic changes in the systemic immune inflammatory index (SII) during the perioperative period of PPCI and evaluate its predictive value for in-hospital and out-of-hospital outcomes in patients with STEMI. METHODS: This retrospective study included 324 consecutive patients with STEMI who were admitted to the cardiac care unit. Blood samples were collected before PPCI, 12 h (T1), 24 h, 48 h after PPCI, the last time before hospital discharge (T2), and 1 month after hospital discharge. The SII was calculated as (neutrophils×platelets)/lymphocytes. Based on whether the primary endpoint occurred, we divided the patients into event and non-event groups. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors that might influence the occurrence of the primary endpoint. Dynamic curves of SII were plotted, and receiver operating characteristic (ROC) curves were drawn for each node to calculate the optimal critical value, sensitivity, and specificity to assess their predictive ability for in-hospital and out-of-hospital courses. Kaplan-Meier curves were used to analyze the differences in survival rates at different SII inflammation levels. RESULTS: High levels of SII were individually related to the occurrence of the in-hospital period and long-term outcomes during the post-operative follow-up of STEMI patients (in-hospital SII: T1:OR 1.001,95%CI 1.001-1.001, P < 0.001; SII following hospital discharge: T1M: OR 1.008,95%CI 1.006-1.010, P < 0.001). Patients with high SII levels had lower survival rates than those with low SII levels. The analysis showed that the SII 12 h after (T1) and SII 1 month (T1M) had excellent predictive values for the occurrence of in-hospital and out-of-hospital outcomes, respectively (AUC:0.896, P < 0.001; AUC:0.892, P < 0.001). CONCLUSION: There is a significant relationship between the dynamic status of SII and prognosis in patients with STEMI. This study found that the 12 h and SII 1 month affected in-hospital and out-of-hospital outcomes, respectively. Consequently, we focused on the dynamic changes in the SII.

Relationship between systemic immune inflammation index and development of complete atrioventricular block in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: The systemic immune-inflammation index (SII), based on white blood cell, neutrophil, and platelet counts, is a proposed marker of systemic inflammation and immune activation. This study aimed to explore the relationship between SII and complete atrioventricular block (CAVB) development in STEMI patients undergoing primary PCI. METHODS: We retrospectively analyzed data from 883 patients who underwent primary PCI for STEMI between January 2009 and December 2017. Patients were categorized into two groups based on CAVB development. SII levels were calculated from blood samples taken on admission. RESULTS: Of the included patients, 48 (5.03%) developed CAVB. SII was higher in patients with CAVB compared to those without CAVB (1370 [1050-1779]x109/L vs. 771 [427-1462] x109/L, p < 0.001). Multivariate analysis showed a significant positive correlation between SII and the risk of CAVB development (OR:1.0003, 95%CI:1.0001-1.0005, P = 0.044). The cut-off value for the SII in the estimation of CAVB was 1117.7 × 109/L (area under the ROC curve [AUC]: 0.714, 95% CI = 0.657-0.770 with a sensitivity of 70.8% and specificity of 65.6%, p < 0.001). CONCLUSION: This study showed a significant link between high SII levels and CAVB development in STEMI patients undergoing PCI. Our findings suggest that SII may be a valuable, routinely available, and inexpensive marker for identifying patients at increased risk of CAVB.

Effect of residual myocardial ischemia on recovery of left ventricular function after primary percutaneous coronary intervention.

BACKGROUND: It is unknown whether the existence of severe bystander damage will affect left ventricular (LV) healing following primary percutaneous coronary intervention (PPCI). The aim of the present analysis was to follow LV recovery using 2D speckle tracking echocardiography (2-D STE) in cases with single versus multiple vessel disease with acute myocardial infarction (AMI) who underwent PPCI and to assess major adverse cardiovascular events (MACEs) within 3 months. PATIENTS AND METHODS: This work was conducted at Assiut University Heart Hospital. Of 1026 screened subjects with AMI needing PPCI and assessed for eligibility, only 89 cases fulfilled the inclusion criteria. They were classified into Group A: single vessel and Group B: multiple vessel (≥ 2 vessels) disease. Their data were obtained on admittance and after 90 days. RESULTS: In group A compared to group B, there was a statistically preferable value at baseline in the global longitudinal strain- Apical 2 chamber (GLS-A2C) (-12.05 ± 3.57 vs. -10.38 ± 3.92, P = 0.039). At follow-up, the improvement was in all 2-D STE variables, including GLS-long axis (GLS-LAX) (-13.09 ± 3.84 vs.-10.75 ± 3.96, P = 0.006), GLS- apical 4 chamber (GLS-A4C) (-13.23 ± 3.51 vs.-10.62 ± 4.08, P = 0.002), GLS-A2C (-13.85 ± 3.41 vs-10.93 ± 3.97, P < 0.001) and GLS- average (GLS-AVG, P = 0.001). There was a considerable negative correlation between the recovery of LV performance and the existence of multi-vessel lesions (P = 0.009). There was no variance between the groups regarding MACEs. CONCLUSIONS: Patients with single vessel lesions who underwent PPCI to the culprit lesion had better recovery of LV function than those with multi-vessel (≥ 2 vessels) lesions who underwent PPCI to the culprit lesion only. The presence of multivessel involvement was an independent risk factor for deterioration in GLS. TRIAL REGISTRATION: Registered in clinical trial, clinicalTrial.gov ID NCT04103008 (25/09/2019). IRB registration: 17,100,834 (05/11/2019).

Prognostic Implications of the Timing of ST-Elevation Myocardial Infarction Development in Relation to COVID-19 Infection.

Background: Patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19 infection have a worse clinical course and prognosis. The prognostic significance of the timing of STEMI in relation to COVID-19 infection was not investigated. Objectives: To assess whether the time of STEMI development in relation to COVID-19 infection (concurrent or following the infection) influenced the short-term prognosis. Methods: This was an observational study of consecutive COVID-19 patients with STEMI admitted to the COVID-hospital Batajnica (February 2021-March 2022). The patients were divided into the "STEMI first" group: patients with STEMI and a positive polymerase chain reaction test for COVID-19, and the "COVID-19 first" group: patients who developed STEMI during COVID-19 treatment. All patients underwent coronary angiography. The primary endpoint was in-hospital all-cause mortality. Results: The study included 87 patients with STEMI and COVID-19 (Mage, 66.7 years, 66% male). The "STEMI first" group comprised 54 (62.1%) patients, and the "COVID-19 first" group included 33 (37.9%) patients. Both groups shared a comparatively high burden of comorbidities, similar angiographic and procedural characteristics, and high percentages of performed percutaneous coronary interventions with stent implantation (90.7% vs. 87.9%). In-hospital mortality was significantly higher in the "COVID-19 first" group compared to the "STEMI first" group (51.5% vs. 27.8%). Following adjustment, the "COVID-19 first" group had a hazard ratio of 3.22 (95% confidence interval, 1.18-8.75, p = .022) for in-hospital all-cause death, compared with the "STEMI first" group (reference). Conclusion: Clinical presentation with COVID-19 infection, followed by STEMI ("COVID-19 first"), was associated with greater short-term mortality compared to patients presenting with STEMI and testing positive for COVID-19 ("STEMI first").

Prevalence and Predictors of Emergency Medical Service Use in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

AIM: We aim to describe prevalence of Emergency Medical Service (EMS) use, investigate factors predictive of EMS use, and determine if EMS use predicts treatment delay and mortality in our ST-elevation myocardial infarction (STEMI) cohort. METHOD: We prospectively collected data on 5,602 patients presenting with STEMI for primary percutaneous coronary intervention (PCI) transported to PCI-capable hospitals in Victoria, Australia, from 2013-2018 who were entered into the Victorian Cardiac Outcomes Registry (VCOR). We linked this dataset to the Ambulance Victoria and National Death Index (NDI) datasets. We excluded late presentation, thrombolysed, and in-hospital STEMI, as well as patients presenting with cardiogenic shock and out-of-hospital cardiac arrest. RESULTS: In total, 74% of patients undergoing primary PCI for STEMI used EMS. Older age, female gender, higher socioeconomic status, and a history of prior ischaemic heart disease were independent predictors of using EMS. EMS use was associated with shorter adjusted door-to-balloon (53 vs 72 minutes, p<0.001) and symptom-to-balloon (183 vs 212 minutes, p<0.001) times. Mode of transport was not predictive of 30-day or 12-month mortality. CONCLUSIONS: EMS use in Victoria is relatively high compared with internationally reported data. EMS use reduces treatment delay. Predictors of EMS use in our cohort are consistent with those prevalent in prior literature. Understanding the patients who are less likely to use EMS might inform more targeted education campaigns in the future.

Regulatory T Cell as Predictor of Intramyocardial Hemorrhage in STEMI Patients after Primary PCI.

Background: Intramyocardial hemorrhage (IMH) is a result of ischemia-reperfusion injury in ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI). Despite patients with IMH show poorer prognoses, studies investigating predictors of IMH occurrence are scarce. This study firstly investigated the effectiveness of regulatory T cell (Treg), peak value of Creatine Kinase MB (pCKMB), high-sensitivity C-reactive protein (hsCRP), and left ventricular end-systolic diameter (LVESD) as predictors for IMH. Methods: In 182 STEMI patients received PPCI, predictors of IMH were analyzed by logistic regression analysis. The predictive ability of risk factors for IMH were determined by receiver operating characteristic curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and C-index. Results: Overall, 80 patients (44.0%) developed IMH. All 4 biomarkers were independent predictors of IMH [odds ratio [OR] (95% confidence interval [CI]): 0.350 (0.202-0.606) for Treg, 1.004 (1.001-1.006) for pCKMB, 1.060 (1.022-1.100) for hsCRP, and 3.329 (1.346-8.236) for LVESD]. After propensity score matching (PSM), the biomarkers significantly predicted IMH with areas under the curve of 0.750 for Treg, 0.721 for pCKMB, 0.656 for hsCRP, 0.633 for LVESD, and 0.821 for the integrated 4-marker panel. The addition of integrated 4-marker panel to a baseline risk model had an incremental effect on the predictive value for IMH [NRI: 0.197 (0.039 to 0.356); IDI: 0.200 (0.142 to 0.259); C-index: 0.806 (0.744 to 0.869), all p < 0.05]. Conclusions: Treg individually or in combination with pCKMB, hsCRP, and LVESD can effectively predict the existence of IMH in STEMI patients received PPCI. Clinical Trial Registration: NCT03939338.

Incidence, Predictors, and Outcome Associated With Ventricular Tachycardia or Fibrillation in Patients Undergoing Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction.

BACKGROUND: The characteristics and clinical outcomes associated with sustained ventricular tachycardia and fibrillation (VT/VF) in Japanese acute myocardial infarction (AMI) patients remain unknown.Methods and Results: Consecutive AMI patients (n=1,941) transferred to the Hirosaki University Hospital and treated with primary percutaneous coronary intervention (PCI) within 12 h of onset were retrospectively studied. The incidence of VT/VF during hospitalization was 8.3%, and 75% of cases occurred by the end of PCI. Independent predictors associated with VT/VF occurrence by the end of PCI and after PCI, respectively, were identified. Additionally, the differences between patients with VT and VF were examined, which revealed that the characteristics of patients and predictors for VT and VF were clearly different. Additionally, the QRS duration during VT was measured, which demonstrated the possible involvement of Purkinje fibers for VT in the acute phase of AMI. Of the patients with VT/VF, 12% required ECMO support due to refractory VT/VF despite intravenous antiarrhythmic agents such as ß-blockers, amiodarone, and nifekalant. Among the patients discharged alive, 1,690 were followed up for a mean of 3.7 years. VT/VF occurrence during hospitalization did not affect the mid-term clinical outcomes even in patients with VT. CONCLUSIONS: The results clearly indicated that VT/VF is still a serious complications of AMI. We need to identify patients at high risk of developing VT/VF for careful observation and appropriate intervention.