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.

STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) guidelines recommend pharmaco-invasive treatment if timely primary percutaneous coronary intervention (PCI) is unavailable. Full-dose tenecteplase is associated with an increased risk of intracranial hemorrhage in older patients. Whether pharmaco-invasive treatment with half-dose tenecteplase is effective and safe in older patients with STEMI is unknown. METHODS: STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) was an investigator-initiated, open-label, randomized, multicenter study. Patients ≥60 years of age with ≥2 mm ST-segment elevation in 2 contiguous leads, unable to undergo primary PCI within 1 hour, were randomly assigned (2:1) to half-dose tenecteplase followed by coronary angiography and PCI (if indicated) 6 to 24 hours after randomization, or to primary PCI. Efficacy end points of primary interest were ST resolution and the 30-day composite of death, shock, heart failure, or reinfarction. Safety assessments included stroke and nonintracranial bleeding. RESULTS: Patients were assigned to pharmaco-invasive treatment (n=401) or primary PCI (n=203). Median times from randomization to tenecteplase or sheath insertion were 10 and 81 minutes, respectively. After last angiography, 85.2% of patients undergoing pharmaco-invasive treatment and 78.4% of patients undergoing primary PCI had ≥50% resolution of ST-segment elevation; their residual median sums of ST deviations were 4.5 versus 5.5 mm, respectively. Thrombolysis In Myocardial Infarction flow grade 3 at last angiography was ≈87% in both groups. The composite clinical end point occurred in 12.8% (51/400) of patients undergoing pharmaco-invasive treatment and 13.3% (27/203) of patients undergoing primary PCI (relative risk, 0.96 [95% CI, 0.62-1.48]). Six intracranial hemorrhages occurred in the pharmaco-invasive arm (1.5%): 3 were protocol violations (excess anticoagulation in 2 and uncontrolled hypertension in 1). No intracranial bleeding occurred in the primary PCI arm. The incidence of major nonintracranial bleeding was low in both groups (<1.5%). CONCLUSIONS: Halving the dose of tenecteplase in a pharmaco-invasive strategy in this early-presenting, older STEMI population was associated with electrocardiographic changes that were at least comparable to those after primary PCI. Similar clinical efficacy and angiographic end points occurred in both treatment groups. The risk of intracranial hemorrhage was higher with half-dose tenecteplase than with primary PCI. If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02777580.

Association of stress hyperglycemia ratio with left ventricular function and microvascular obstruction in patients with ST-segment elevation myocardial infarction: a 3.0 T cardiac magnetic resonance study.

BACKGROUND: Stress hyperglycemia, which is associated with poor prognosis in patients with acute myocardial infarction (AMI), can be determined using the stress hyperglycemia ratio (SHR). Impaired left ventricular function and microvascular obstruction (MVO) diagnosed using cardiac magnetic resonance (CMR) have also been proven to be linked to poor prognosis in patients with AMI and aid in risk stratification. However, there have been no studies on the correlation between fasting SHR and left ventricular function and MVO in patients with acute ST-segment elevation myocardial infarction (ASTEMI). Therefore, this study aimed to investigate the additive effect of fasting SHR on left ventricular function and global deformation in patients with ASTEMI and to explore the association between fasting SHR and MVO. METHODS: Consecutive patients who underwent CMR at index admission (3-7 days) after primary percutaneous coronary intervention (PPCI) were enrolled in this study. Basic clinical, biochemical, and CMR data were obtained and compared among all patients grouped by fasting SHR tertiles: SHR1: SHR < 0.85; SHR2: 0.85 ≤ SHR < 1.01; and SHR3: SHR ≥ 1.01. Spearman's rho (r) was used to assess the relationship between fasting SHR and left ventricular function, myocardial strain, and the extent of MVO. Multivariable linear regression analysis was performed to evaluate the determinants of left ventricular function and myocardial strain impairment in all patients with AMI. Univariable and multivariable regression analyses were performed to investigate the correlation between fasting SHR and the presence and extent of MVO in patients with AMI and those with AMI and diabetes mellitus (DM). RESULTS: A total of 357 patients with ASTEMI were enrolled in this study. Left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI) were significantly lower in SHR2 and SHR3 than in SHR1. Compared with SHR1 and SHR2 groups, left ventricular strain was lower in SHR3, as evidenced by global radial (GRS), global circumferential (GCS), and global longitudinal (GLS) strains. Fasting SHR were negatively correlated with LVEF, LVGFI, and GRS (r = - 0.252; r = - 0.261; and r = - 0.245; all P<0.001) and positively correlated with GCS (r = 0.221) and GLS (r = 0.249; all P <0.001). Multivariable linear regression analysis showed that fasting SHR was an independent determinant of impaired LVEF, LVGFI, GRS, and GLS. Furthermore, multivariable regression analysis after adjusting for covariates signified that fasting SHR was associated with the presence and extent of MVO in patients with AMI and those with AMI and DM. CONCLUSION: Fasting SHR in patients with ASTEMI successfully treated using PPCI is independently associated with impaired cardiac function and MVO. In patients with AMI and DM, fasting SHR is an independent determinant of the presence and extent of MVO.

Impact of acute glycemic variability on short-term outcomes in patients with ST-segment elevation myocardial infarction: a multicenter population-based study.

BACKGROUND: Given the increasing attention to glycemic variability (GV) and its potential implications for cardiovascular outcomes. This study aimed to explore the impact of acute GV on short-term outcomes in Chinese patients with ST-segment elevation myocardial infarction (STEMI). METHODS: This study enrolled 7510 consecutive patients diagnosed with acute STEMI from 274 centers in China. GV was assessed using the coefficient of variation of blood glucose levels. Patients were categorized into three groups according to GV tertiles (GV1, GV2, and GV3). The primary outcome was 30-day all-cause death, and the secondary outcome was major adverse cardiovascular events (MACEs). Cox regression analyses were conducted to determine the independent correlation between GV and the outcomes. RESULTS: A total of 7136 patients with STEMI were included. During 30-days follow-up, there was a significant increase in the incidence of all-cause death and MACEs with higher GV tertiles. The 30-days mortality rates were 7.4% for GV1, 8.7% for GV2 and 9.4% for GV3 (p = 0.004), while the MACEs incidence rates was 11.3%, 13.8% and 15.8% for the GV1, GV2 and GV3 groups respectively (p < 0.001). High GV levels during hospitalization were significantly associated with an increased risk of 30-day all-cause mortality and MACEs. When analyzed as a continuous variable, GV was independently associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.679, 95% confidence Interval [CI] 1.005-2.804) and MACEs (HR 2.064, 95% CI 1.386-3.074). Additionally, when analyzed as categorical variables, the GV3 group was found to predict an increased risk of MACEs, irrespective of the presence of diabetes mellitus (DM). CONCLUSION: Our study findings indicate that a high GV during hospitalization was significantly associated with an increased risk of 30-day all-cause mortality and MACE in Chinese patients with STEMI. Moreover, acute GV emerged as an independent predictor of increased MACEs risk, regardless of DM status.

Combined risk estimates of diabetes and coronary angiography-derived index of microcirculatory resistance in patients with non-ST elevation myocardial infarction.

BACKGROUND: Diabetes mellitus (DM) and coronary microvascular dysfunction (CMD) increase the risk of adverse cardiac events in patients with non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to evaluate the combined risk estimates of DM and CMD, assessed by the angiography-derived index of microcirculatory resistance (angio-IMR), in patients with NSTEMI. METHODS: A total of 2212 patients with NSTEMI who underwent successful percutaneous coronary intervention (PCI) were retrospectively enrolled from three centers. The primary outcome was a composite of cardiac death or readmission for heart failure at a 2-year follow-up. RESULTS: Post-PCI angio-IMR did not significantly differ between the DM group and the non-DM group (20.13 [17.91-22.70] vs. 20.19 [18.14-22.77], P = 0.530). DM patients exhibited a notably higher risk of cardiac death or readmission for heart failure at 2 years compared to non-DM patients (9.5% vs. 5.4%, P < 0.001). NSTEMI patients with both DM and CMD experienced the highest cumulative incidence of cardiac death or readmission for heart failure at 2 years (24.0%, P < 0.001). The combination of DM and CMD in NSTEMI patients were identified as the most powerful independent predictor for cardiac death or readmission for heart failure at 2 years (adjusted HR: 7.894, [95% CI, 4.251-14.659], p < 0.001). CONCLUSIONS: In patients with NSTEMI, the combination of DM and CMD is an independent predictor of cardiac death or readmission for heart failure. Angio-IMR could be used as an additional evaluation tool for the management of NSTEMI patients with DM. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT05696379.

Optional Revascularization Strategies for Patients with ST-Segment Elevation Myocardial Infarction and Multivessel Disease.

Percutaneous coronary intervention is the main strategy of revascularization and has been shown to improve outcomes in some patients with ST-segment elevation myocardial infarction (STEMI). However, multivessel disease (MVD), a common condition in these patients, is associated with worse clinical outcomes compared to single-vessel disease. Despite intervention being a standard treatment for coronary artery disease, optimal strategies and timings for patients with STEMI and MVD remain unclear. Numerous studies and meta-analyses have investigated this topic; however, many current conclusions are based on observational studies. Furthermore, clinical guidelines regarding the management of patients with STEMI and MVD contain conflicting recommendations. Therefore, we aimed to compile relevant studies and newly available evidence-based medicines to explore the most effective approach.

Efficacy and Safety of Deferred Stenting in Geriatric Patients with STEMI and High Thrombus Burden.

Background: Deferred stenting has been recognized as beneficial for patients with acute ST-segment elevation myocardial infarction (STEMI) accompanied by a high thrombus burden. Nevertheless, its efficacy and safety specifically in geriatric STEMI patients remain to be elucidated. This study aims to bridge this knowledge gap and assess the potential advantages of deferred stenting in an older patient cohort. Methods: In this study, 208 geriatric patients (aged ≥ 80 years) with STEMI and a high thrombus burden in the infarct-related artery (IRA) were enrolled. They were categorized into two groups: the deferred stenting group, where stent implantation was conducted after 7-8 days of continuous antithrombotic therapy, and the immediate stenting group, where stent implantation was performed immediately. Results: In the deferred stenting group, the stents used were significantly larger in diameter and shorter in length compared to those in the immediate stenting group (p < 0.05). This group also exhibited a lower incidence of distal embolism in the IRA, and higher rates of the thrombolysis in myocardial infarction (TIMI) blood flow grade 3 and myocardial blush grade 3 (p < 0.05). Additionally, the left ventricular ejection fractions at the 1-year follow-up were significantly higher in the deferred stenting group than in the immediate stenting group (p < 0.05). The rate of the major adverse cardiac events in the deferred stenting group was significantly lower than in the immediate stenting groups (p < 0.05). Conclusions: Deferred stenting for geriatric patients with STEMI and high thrombus burden demonstrates significant clinical benefits. This approach not only reduces the incidence of distal embolism in the IRA, but also enhances myocardial tissue perfusion and preserves cardiac ejection function. Moreover, deferred stenting has proven to be safe in this patient population, indicating its potential as a preferred treatment strategy in such cases.

Coronary Microvascular Function Assessment using the Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients with ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Background: Studies reporting the status of coronary microvascular function in the infarct-related artery (IRA) after primary percutaneous coronary intervention (PCI) remain limited. This study utilized the coronary angiography-derived index of microcirculatory resistance (caIMR) to assess coronary microvascular function in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. Methods: We used the FlashAngio system to measure the caIMR after primary PCI in 157 patients with STEMI. The primary endpoint was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite endpoint encompassing cardiac mortality, target vessel revascularization, and rehospitalization due to congestive heart failure (CHF), myocardial infarction (MI), or angina. Results: Approximately 30% of patients diagnosed with STEMI and who experienced successful primary PCI during the study period had a caIMR in the IRA of > 40. The caIMR in the IRA was significantly higher than in the reference vessel (32.9 ± 15.8 vs. 27.4 ± 11.1, p < 0.001). The caIMR in the reference vessel of the caIMR > 40 group was greater than in the caIMR ≤ 40 group (30.9 ± 11.3 vs. 25.9 ± 10.7, p = 0.009). Moreover, the caIMR > 40 group had higher incidence rates of MACEs at 3 months (25.5% vs. 8.3%, p = 0.009) and 1 year (29.8% vs. 13.9%, p = 0.04), than in the caIMR ≤ 40 group, which were mainly driven by a higher rate of rehospitalization due to CHF, MI, or angina. A caIMR in the IRA of > 40 was an independent predictor of a MACE at 3 months (hazard ratio (HR): 3.459, 95% confidence interval (CI): 1.363-8.779, p = 0.009) and 1 year (HR: 2.384, 95% CI: 1.100-5.166, p = 0.03) in patients with STEMI after primary PCI. Conclusions: Patients with STEMI after primary PCI often have coronary microvascular dysfunction, which is indicated by an increased caIMR in the IRA. An elevated caIMR of > 40 in the IRA was associated with an increased risk of adverse outcomes in STEMI patients undergoing primary PCI.

Myocardial Infarction in Chronic Myeloid Leukemia: Results from the Nationwide Readmission Database.

INTRODUCTION: Chronic myeloid leukemia (CML) is a hematological malignancy with an excellent prognostic outcome. After the advancements in CML treatment and the introduction of different tyrosine kinase inhibitors (TKIs), the life expectancy of CML patients has become equivalent to that of the general population. As a result, coronary artery disease is anticipated to be the leading cause of death among CML patients. Moreover, TKI use is associated with a risk of endothelial dysfunction, thrombosis, and cardiovascular events, including myocardial infarction. In this study, we compare the outcomes of percutaneous coronary intervention (PCI) in patients with CML to their matched non-CML counterparts. METHOD: This is a retrospective cohort study using the Nationwide Readmission Database from January 2016 to December 2020. Adults with or without CML hospitalized for acute myocardial infarction and underwent PCI were included. The patients were identified using ICD-10 codes. The primary outcomes were in-hospital mortality and 30-day readmission rates. The secondary outcomes were PCI complications rates. RESULTS: Out of 2,727,619 patients with myocardial infarction, 2,124 CML patients were identified. A total of 888 CML patients underwent PCI. CML patients were significantly older (mean age: 68.34 ± 11.14 vs. 64.40 ± 12.61 years, p < 0.001) than non-CML patients without a difference in sex distribution. Hypertension (85.45% vs. 78.64%), diabetes (45.48% vs. 37.29), stroke (11.84% vs. 7.78) at baseline were significantly higher in the CML group. Prior myocardial infarction events (20.51% vs. 15.17%) and prior PCI procedure (24.47% vs. 16.89%) were significantly higher in the CML group. CML patients had a significantly longer hospital stay (4.66 ± 4.40 vs. 3.75 ± 4.62 days, p = 0.001). The primary outcomes did not differ between the comparison groups. The risk of post-PCI complications did not differ between the comparison groups in the propensity matched analysis except for coronary artery dissection (odds ratio [OR]: 0.10; 95% confidence interval [CI]: 0.02-0.65, p = 0.016) and ischemic stroke (OR: 0.35; 95% CI: 0.14-0.93, p = 0.034) which were lower in the CML group. CONCLUSION: This analysis showed no statistically significant difference in mortality, 30-day readmission, and post PCI complications rates between CML and non-CML patients. However, interestingly, CML patients may experience lower coronary artery dissection and ischemic stroke events than those without CML diagnosis.

MR Uniformity Ratio Estimates to Evaluate Ventricular Mechanical Dyssynchrony and Prognosis After ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear. HYPOTHESIS: MR uniformity ratio estimates (URE) can detect LVMD and assess STEMI prognosis. STUDY TYPE: Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453). POPULATION: Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls. FIELD STRENGTH/SEQUENCE: 3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging. ASSESSMENT: MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared. STATISTICAL TESTS: The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant. RESULTS: CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF. DATA CONCLUSION: CURE and RURE may be useful to evaluate long-term prognosis after STEMI. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.