Acute Phase Of ST-elevation Myocardial Infarction Research Articles

Immature Platelet Fraction and Acute Coronary Syndrome; a Systematic Review and Meta-Analysis.

Immature Platelet Fraction (IPF) is a measure of the proportion of reticulated platelets (RPs) to all platelets in circulation. IPF may have both prognostic and diagnostic values in patients with Acute Coronary Syndrome (ACS). This study aims to comprehensively summarize the diagnostic utility of IPF levels in patients with ACS, specifically focusing on its ability to differentiate between different subtypes of ACS. We conducted a systematic search in online databases including MEDLINE, Scopus, and Google Scholar up to March 4th 2024, to identify relevant studies. The random-effect model, employing inverse variance for mean differences (MD) and Mantel-Haenszel methods for odds ratios (OR) were utilized to combine the data. Joanna Briggs Institute (JBI) appraisal tool was employed to assess the quality of included studies. Our systematic review contains 15 articles with a total sample size of 2,030 ACS patients. Pooled analysis revealed significant differences in IPF levels of ACS patients compared to healthy controls (MD (95%CI): 2.85 (0.86, 4.85), P-value = 0.004) and stable angina patients (MD (95%CI): 0.58 (0.23, 0.92), P-value < 0.001). Subgroup comparisons within ACS patients demonstrated higher IPF levels in myocardial infarction (MI) vs. unstable angina (UA) (MD (95%CI): 1.81 (0.41, 3.22), P-value = 0.01), ST elevation MI (STEMI) vs. non-ST elevation (NSTEMI) ACS (MD (95%CI): 0.74 (0.31, 1.17), P-value < 0.001), and NSTEMI vs. UA (MD (95% CI): 1.07 (0.24, 1.90), P-value = 0.01). IPF levels could increase in patients with ACS, particularly during the acute phase of STEMI. This suggests that IPF may be a useful biomarker for early diagnosis of ACS. Additionally, IPF levels may help differentiate between ACS subtypes.

Abstract 13947: Heparin-Mediated Release of Hepatocyte Growth Factor at the Acute Phase of STEMI

Introduction: Hepatocyte Growth Factor (HGF) is a cytokine promoting cell survival via its receptor c-met. Heparin injection is known to induce a massive release of native HGF in blood. Heparin is used at the acute phase of myocardial infarction (MI). However, HGF release at the acute phase of MI and its potential cardioprotective effect is unknown. Hypothesis: We aimed to assess HGF kinetics in a cohort of ST-elevation myocardial infarction (STEMI) and its potential cardioprotective effect. Methods: We prospectively included consecutive STEMI patients admitted in our hospital from 2016 to 2019. All patients underwent coronary angiography with revascularization. Sera were collected at 5 time points (admission, 4 hours (H4), H24, H48 and 1 month after STEMI). Samples were stored at -80°C. HGF levels were assess by ELISA. We used a mouse model of myocardial ischemia reperfusion (ligation of the left anterior descending coronary artery followed by reperfusion) to evaluate HGF effect. Results: We included 230 patients. We observed an intense and early peak of HGF as early as admission, before revascularization (8750 pg/ml, IQR [8021-9492]) followed by a rapid decrease within the first 48h (p&lt;0.0001). We demonstrated that this rapid increase was induced by heparin administration (unfractionated heparin or low molecular weight heparins). To evaluate the effect of HGF on myocardial infarct size we administrated HGF or placebo in mice during myocardial reperfusion. In the HGF group, infarct size was significantly smaller compared to the control group (52.0% of left ventricle vs 58.0%, p=0.002). Conclusions: We demonstrated an intense and early HGF peak at the acute phase of STEMI, induced by heparin. In our preclinical mouse model, HGF had cardioprotective effect after MI. Thus we may suppose that heparin-mediated release of HGF at the acute phase of STEMI have cardioprotective effect that may confer a basal cardioprotection in all patients.

Reticulated Platelets and Their Relationship with Endothelial Progenitor Cells during the Acute Phase of ST-Elevation Myocardial Infarction.

Endothelial progenitor cells (EPC) and reticulated platelets (RP) have central roles in the thrombotic and angiogenetic interactions during ST-elevation myocardial infarction (STEMI). The EPC and RP response in patients with STEMI treated by primary percutaneous intervention (PPCI) has not yet been investigated. We assessed EPC quantification by the expression of CD133+ and CD34+, and EPC function by the capacity of the cells to form colony-forming units (CFU) and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) during the acute phase of STEMI. These measurements were correlated with RP at baseline and after 24 h following PPCI. Our cohort included 89 consecutive STEMI-diagnosed patients enrolled between December 2018 and July 2021. At baseline, there was a strong positive correlation between reticulated platelet quantity and MTT levels (R = 0.766 and R2 = 0.586, p &lt; 0.001), CD34+ levels (R = 0.602, and R2 = 0.362, p &lt; 0.001); CD133+ levels (R = 0.666 and R2 = 0.443, p &lt; 0.001) and CFU levels (R = 0.437, R2 = 0.191, p &lt; 0.001). The multiple linear regression showed that levels of MTT (adjusted R2 = 0.793; p &lt; 0.001), CD34+ and CD133+ (adjusted R2 = 0.654; p &lt; 0.001 and adjusted R2 = 0.627; p &lt; 0.001, respectively) had strong independent correlations with RP response. At 24 h after PPCI, the correlation between RP quantity and EPC markers was not significant, except for MTT levels (R = 0.465, R2 = 0.216, p &lt; 0.001). In patients with STEMI, higher levels of RP at baseline are significantly correlated with a more potent EPC response. The translational significance of these findings needs further investigation.

Correlation and prognostic ability of admission lung ultrasound and late peak atrial longitudinal strain in patients with ST-elevation myocardial infarction

Abstract Background Acute heart failure is common after ST-elevation myocardial infarction (STEMI), leading to lung congestion. Speckle tracking echocardiography has increased sensitivity to detect subclinical myocardial compliance disorders and may help to better understand the physiopathology in this setting. Purpose This study sought to determine the correlation and prognostic ability of admission lung congestion evaluated by lung ultrasound (LUS) and peak atrial longitudinal strain (PALS) performed after the acute phase of STEMI. Methods This was a prospective cohort of STEMI patients treated in a tertiary care hospital. LUS was performed by two independent operators before primary percutaneous coronary intervention (PCI). Our protocol consisted of eight scanning sites, which were considered positive for congestion if there were three or more B-lines in at least one site. Echocardiography was performed in all patients 2–4 days after STEMI, and the images were interpreted offline by two operators blinded to LUS findings. PALS &amp;lt;30 was considered abnormally reduced atrial contraction. Major cardiovascular events (MACE) were considered as new myocardial infarction, stroke or death in 30 days. Results Of the 339 patients admitted with STEMI, 208 (61%) performed LUS and had interpretable PALS. The mean age was 61 (±12) years and 65% were male. Lung congestion was present in 48% patients. Mean left ventricular ejection fraction (LVEF) was 49%, 21% of patients had EF&amp;lt;40%. Pearson correlation between the number of positive LUS sites and PALS was 0.18 (P=0.029). A subanalysis including only patients with left ventricle ejection fraction &amp;gt;50% showed similar results (correlation 0.10, P=0.349). All 10 (5%) patients with unsuccessful primary PCI had PALS &amp;lt;30. No patients with PALS&amp;gt;30 experienced 30-day MACE, while patients with PALS &amp;lt;30 with and without lung congestion had 1.6% and 13.8% 30-day MACE, respectively. Conclusion In a cohort of STEMI patients, the correlation of positive LUS sites and the PALS was low. Impaired PALS was associated with unsuccessful primary PCI, while normal PALS was associated with uneventful follow-up. The PALS assessment in addition to LUS profile was able to identify patients at higher risk for MACE. Although timing difference between lung ultrasound and echocardiography is a limitation of this analysis, our findings are consistent with the “lung water cascade theory”. Funding Acknowledgement Type of funding sources: None.

The role of IL-6 receptor trans-signalling in ischemia-reperfusion injury, infarct healing and future adverse events in patients with ST-Elevation Myocardial Infarction

Abstract Background Inflammation has emerged as a new treatment target in patients with coronary artery disease, and inflammation seems to play an important role in the ischemia/reperfusion injury in ST-elevation myocardial infarction (STEMI). The pro-inflammatory cytokine interleukin-6 (IL-6) has been shown to be associated with myocardial injury and poor prognosis in patients with STEMI. Purpose The aim of the study was to further elucidate possible associations between the IL-6 trans-signalling system and final infarct size, myocardial function, adverse remodelling, and future cardiovascular events in patients with STEMI. Methods A total of 272 patients with first-time STEMI included in the POSTEMI study on ischaemic postconditioning, with symptom duration &amp;lt;6 hours and treated with percutaneous coronary intervention (PCI), were included. Blood samples for analysis of IL-6 and IL-6 receptor (IL-6R) were collected before PCI, immediately after PCI, at day 1 (median 18.3 hours after PCI), and at 4 months follow-up. Cardiac magnetic resonance imaging (CMR) was performed in the acute phase, median 2 days after admission, and repeated after 4 months. Clinical events and all-cause mortality were registered during 12 months' and 70 months' follow-up, respectively. Results There was a significant increase in IL-6 levels from admission to day 1 with a subsequent decline from day 1 to 4 months (Figure 1A). No significant change in IL-6R levels were found from admission to day 1 (Figure 1B). There was no difference between patients treated by postconditioning compared to routine PCI. High levels of IL-6 (&amp;gt; median) at all sampling points were significantly associated with increased infarct size and reduced left ventricular ejection fraction (LVEF) measured by CMR. Additionally, high levels of IL-6 (&amp;gt; median) at day 1 were associated with lower myocardial salvage, more presence of microvascular obstruction and larger increase in indexed LV end diastolic volume (LVEDVi). IL-6R measured during hospitalisation was significantly associated with change in LVEDVi, but did not associate with infarct size, LVEF or myocardial salvage. High levels of IL-6 (&amp;gt;75th percentile) at all sampling points were associated with an increased risk of having an adverse clinical event during the first year and with long-term all-cause mortality (Figure 2), whereas there was no association between IL-6R and adverse clinical events. Conclusion Patients with high IL-6 levels during the acute phase of STEMI had larger infarct size, reduced myocardial salvage, reduced LV function and worse clinical outcome than patients with lower levels of IL-6. High levels of IL-6 measured after 4 months were associated with larger infarct size, reduced LVEF and increased all-cause mortality. IL-6R was significantly associated with increase in LVEDVi. The results add important information to the role of IL-6 in myocardial injury in acute STEMI and the IL-6 pathway as a potential treatment target. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Stein Erik Hagen Foundation for Clinical Heart Research, Oslo, Norway. Figure 1Figure 2

Prognostic implications of left ventricular torsion by feature-tracking cardiac magnetic resonance in patients with ST-elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the National Key Research and Development Program of China OnBehalf Renji Hospital Affiliated to Medical College of Shanghai Jiaotong University Background The prognostic implications of left ventricular (LV) torsion on the long-term prognosis of patients with acute ST-elevation myocardial infarction (STEMI) is not clear. Methods We analyzed Cardiac Magnetic Resonance (CMR) images and followed up 420 first STEMI patients from the EARLY Assessment of MYOcardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). These patients received timely primary percutaneous coronary intervention (PCI) within 12h and CMR examination within 1 week (median,5 days; range, 2-7 days) after infarction. Besides, CMR images of 40 normal people were enrolled as the control group. LV torsion, torsion rate and other conventional CMR indexes were measured. Ultrasound cardiogram examinations were performed in the acute phase and 1 year post-STEMI to assess LV remodeling (≥ 20% increase in LV end-diastolic volume). Primary end point was composite major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, re-hospitalization for heart failure and stroke. Secondary end points were the formation of LV aneurysm/thrombus in hospital as well as LV remodeling at 1 year post-STEMI. Results During follow-up (median: 52 months, inter-quartile range: 29–78 months), 80 patients developed MACCEs. Compared with normal people, patients with STEMI had more decreased LV torsion (P &amp;lt; 0.001) and torsion rate (P = 0.033). Patients who experienced MACCEs had more impaired LV torsion (P &amp;lt; 0.001) and torsion rate (P &amp;lt; 0.001) than those who didn’t. LV torsion ≤ 0.876 deg/cm in the acute phase of STEMI was an independent predictive factor of MACCE (P = 0.001) and LV remodeling (P = 0.001). Patients with impaired LV torsion were more likely to experience MACCEs (P &amp;lt; 0.001). The impairment of LV torsion was also associated with the higher incidence of LV aneurysm (P &amp;lt; 0.001) and thrombus (P = 0.006). The addition of LV torsion to a risk model comprising LV ejection fraction (LVEF), infarct size (IS), and microvascular obstruction (MVO) led to a net reclassification improvement (continuous NRI 0.499 [95% CI, 0.261–0.737]; P &amp;lt; 0.001). Hypertension (P = 0.047), tobacco use (P = 0.005), worse TIMI flow post-PCI (P &amp;lt; 0.001), more extensive IS (P &amp;lt; 0.001) / MVO size (P = 0.002) were associated with the impairment of LV torsion. Conclusions Compared with normal people, patients with STEMI had more decreased LV torsion and torsion rate. LV torsion ≤ 0.876 deg/cm in the acute phase was an independent predictive factor of MACCE and LV remodeling. The addition of LV torsion to a risk model comprising LVEF, LV-IS and LV-MVO significantly improved risk stratification of patients with STEMI .

Defective Allele of the Neuronal Nitric Oxide Synthase Gene Increases Insulin Resistance During Acute Phase of Myocardial Infarction.

BackgroundGlycemic disorders are strong predictors of mortality in ST-elevation myocardial infarction (STEMI) patients, and disruption in nitric oxide (NO) production is associated with insulin-resistant states. We evaluated whether a defective allele of the neuronal nitric oxide synthase (nNOS) gene (NOS1) might influence insulin response and blood-glucose balance during the acute phase of STEMI and if post-infarction total plasma-NO levels and vasodilation scores varied across nNOS genotypes.MethodsConsecutive patients with STEMI (n=354) underwent clinical evaluations and genotyping for the promoter variation rs41279104. In-hospital clinical and blood evaluations were performed at admission and five days after STEMI, with glycemic, insulinemic, and disposition indices assessed at the same times. Flow-mediated dilation (FMD) was assessed by reactive hyperemia on the 30th day.ResultsHomozygotes for the defective allele (A) showed lower glycemia and insulin sensitivity on day 1 while showing the highest β-cell function and no changes in the circulating NO pool, which is compatible with hyperresponsive β cells counteracting the inherent glucose-resistant state of AA patients. At day 5, glycemic scores had shifted to indicate greater insulin sensitivity among A homozygotes, paralleled by a significant yet poor increase in NO bioavailability compared to that among G carriers. All in all, defective homozygotes showed greater insulin resistance at admission that had reversed by 5 days after STEMI. Even so, A carriers developed lower FMD scores compared to G homozygotes after the acute phase.ConclusionA defective nNOS allele (and due decline in NO production) seemed to elicit a hyperinsulinemia response to compensate for an insulin-resistant state during the acute phase of STEMI and to be associated with poor endothelial function after the acute phase.

Risk definition and outcomes with the application of the PEGASUS-TIMI 54 trial inclusion criteria to a \u201creal world\u201d STEMI population: results from the Italian \u201cCARDIO-STEMI SANREMO\u201d registry

BackgroundThe PEGASUS-TIMI 54 trial inclusion criteria effectively identified high-risk patients with recent myocardial infarction (MI) who would benefit from continuing dual antiplatelet therapy (DAPT) with ticagrelor for more than 12 months. It is unknown how many real-world patients meet these criteria during the acute phase of ST-elevation MI (STEMI), or the extent to which these criteria predict a patient's risk and prognosis. Study objectives were: (1) determine the proportion of PEGASUS-TIMI 54-like patients (PG-l) in a real-world cohort of patients hospitalized with STEMI and to assess their ischemic and hemorrhagic risk; (2) examine their ischemic and hemorrhagic in-hospital events (major adverse cardiovascular and cerebrovascular events [MACCE] and clinically relevant bleeding); (3) evaluate their long-term outcomes and the impact on the long-term prognosis of the type of DAPT prescribed at discharge.MethodsThis observational study was conducted in 1086 patients admitted to hospital with a diagnosis of STEMI between February 2011 and March 2018 and enrolled in the CARDIO-STEMI Sanremo registry. Patients’ demographic and clinical characteristics, procedural variables, and individual ischemic and hemorrhagic risk scores were assessed in-hospital. Four-year survival was also analyzed.ResultsThe proportion of PG-I patients was 69.2%. Compared with non-PG-l patients, PG-l patients were older, had more multivessel disease and comorbidities, and experienced more frequent MACCE (8.3% vs. 3.6%, p = 0.005) and clinically significant bleeding events (6.7% vs. 2.7%, p = 0.008), a higher rate of in-hospital death (6.5% vs. 1.5%, p < 0.001), and higher follow-up mortality rate (14.8% vs. 7.7%; p = 0.002). Four-year survival was significantly lower in the PG-l group (83.9% vs. 91.8%; Log-rank = 0.001) and was related to the cumulative number of concurrent risk factors. In the unadjusted analysis, survival was greater in patients discharged on ticagrelor than on another P2Y12 inhibitor (90.2% vs. 76.7%, Log-rank = 0.001), and the difference was particularly evident in PG-l patients.ConclusionsThe risk of MACCE for PG-l patients increased with the number of concurrent PEGASUS-TIMI 54 risk features. Treatment with ticagrelor on discharge was associated with improved survival rates during 4 years of follow-up.

Bridging the gap: Current and future insights for improving suboptimal platelet inhibition in STEMI

Antiplatelet therapy is one of the cornerstones in the acute treatment of patients with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI). However, hemodynamic changes and delayed intestinal absorption of P2Y12 inhibitors leads to a delay in the onset of antiplatelet effects resulting in a gap of platelet inhibition. Several strategies have been proposed to bridge this gap, such as pre-hospital administration of antiplatelet therapy, higher loading doses of P2Y12 inhibitors, crushing or chewing tablets, subcutaneous or intravenous administration of platelet inhibitors, or use of pain relievers alternative to opioids that do not delay intestinal absorption of oral platelet inhibitors. These strategies may improve platelet inhibition with the goal of optimizing clinical outcomes in the acute phase of STEMI. In this review we present current and future insights for bridging the gap in platelet inhibition in STEMI patients undergoing primary PCI.

Efficacy of early intravenous landiolol, an ultrashort-acting beta-blocker on infarct size and its safety in patients with myocardial infarction undergoing primary PCI: a randomized, controlled study

Abstract Background Previous clinical studies showed that early intravenous metoprolol before reperfusion in patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI reduced infarct size. However, intravenous beta-blockers in acute phase of STEMI can be associated with adverse effects such as cardiogenic shock and atrioventricular block. Landiolol is an ultrashort-acting beta-blocker with a half-life of 3 min that is eight times more cardioselective than esmolol. Purpose We evaluate the efficacy of intravenous infusion of landiolol on infarct size and its safety in STEMI patients undergoing primary PCI. Methods This study is a multicenter randomized control trial. A total of 47 patients with Killip class II or less STEMI undergoing PCI within 12 hours of symptoms onset were randomized to receive intravenous landiolol (n=23) or not (control, n=24). Patients allocated to landiolol group delivered an intravenous continuous dose of 3μg/min/kg before reperfusion and then continued until a total dose of 50mg. All patients started oral metoprolol or carvedilol within 12 hours. The primary end point was myocardial salvage index (MSI) on magnetic resonance imaging performed 5 to 7 days after PCI. MSI was defined as the difference between the area at risk and the area of necrosis analyzed using a commercial software. Results Magnetic resonance imaging was performed in 35 patients (17 patients in landiolol group and 18 patients in the control group), and ischemia duration time was 229 minutes in the landiolol group and the 242 minutes in control. In adjusting for confounding variables, the areas of myocardium at risk were not difference in both groups (54.4g in the landiolol group, and 46.8g in the control group; p=0.31). However, MSI in the landiolol group was significantly reduced than that in the control group (36.8% and 57.0%; p&amp;lt;0.001). In both group blood pressure was not difference in recruitment (142mmHg in landiolol group, and 144 in control) and starting PCI (163mmHg in landiolol group, and 165 in control). Regarding safety, the composite of death, malignant ventricular arrhythmia, cardiogenic shock, and atrioventricular block at 24 hours did not differ between the landiolol and the control groups (8.7% and 8.3%, respectively, p=0.93). Conclusion Early intravenous landiolol before starting primary PCI reduced infarct size in STEMI patients without significant hemodynamic adverse effects. Funding Acknowledgement Type of funding source: None

COMPARison of pre-hospital CRUSHed vs. uncrushed Prasugrel tablets in patients with STEMI undergoing primary percutaneous coronary interventions: Rationale and design of the COMPARE CRUSH trial

Dual antiplatelet therapy constitutes the cornerstone of medical treatment in patients with ST elevation myocardial infarction (STEMI). However, oral antiplatelet agents, such as prasugrel or ticagrelor, are characterized by slow gastrointestinal drug absorption in the acute phase of STEMI, leading to decreased bioavailability and therefore delayed onset of platelet inhibition. Evidence suggests that administration of crushed tablets of the P2Y12 inhibitor prasugrel improves drug absorption and achieves earlier antiplatelet effects in STEMI patients undergoing primary percutaneous coronary intervention (PCI). However, the clinical implications of these pharmacokinetic and pharmacodynamic findings are unknown. The present study is designed to test the hypothesis that patients presenting with STEMI planned for primary PCI will have improved markers of optimal reperfusion and clinical outcomes by prehospital administration of crushed tablets of prasugrel loading dose. COMPARE CRUSH (NCT03296540) is a randomized trial in a regionally organized ambulance care setting evaluating the efficacy and safety of pre-hospital loading dose with prasugrel crushed tablets versus integral tablets in approximately 674 patients presenting with STEMI planned for primary PCI. The independent primary endpoints are percentage of patients reaching thrombolysis in myocardial infarction (TIMI) flow grade 3 in the infarct-related artery at initial angiography, or achieving ≥70% ST-segment elevation resolution at 1 hour post-PCI. Secondary clinical endpoints are death, myocardial infarction, revascularization, and stent thrombosis followed up to 1 year. Moreover, the primary safety endpoint is bleeding events assessed at 48 hours. The COMPARE CRUSH trial will assess whether prehospital administration of loading dose prasugrel in form of crushed tablets - which is expected to provide faster platelet inhibition compared to standard treatment with integral tablets - results in improved reperfusion and clinical outcomes. RCT# NCT03296540.

P773 Can strain imaging predict viability in ST segment elevation myocardial infarction patient

Abstract Background In the acute phase of ST elevation myocardial infarction (STEMI), the main objective is to recanalize the guilty artery, but it is important to know whether myocardium with severely compromised function is permanently injured or reversibly dysfunctional indicating myocardial viability. On the other hand, viability tests such as scintigraphy, magnetic resonance imaging with delayed enhanced (DE-MRI) or dobutamine stress echography are either not validated or unavailable in the acute phase of STEMI. The assessment of myocardial deformation by bidimensional strain (2D) is a technique that has emerged in recent years with good correlation with MRI for viability assessment. An important question remains : Is myocardial viability can be determined by 2D strain parameters at the acute phase of STEMI ? Aim : To assess myocardial viability in the acute phase of STEMI by 2D strain echocardiographic parameters in comparison with 3 month DE-MRI as a reference method. Methods A total of 31 first STEMI patients treated with successful primary or elective percutaneous coronary intervention (PCI) were included with an akinetic area on echocardiography corresponding to the infarct segments. Doppler strain values from left ventricular basal, mid and apical segments (n= 527) were obtained at the acute phase of STEMI and checked up after 3 months. The scar was assessed for viability by DE-MR as reference method, 3 months after the acute phase. Viability was defined by a DE &amp;lt; 50% of wall thickness in the scar zone. Results Mean age of the study population was 59,29 ±9,96 years , 27 (87%) being males. Nine patients (29%) showed post-PCI improvement of left ventricule (LV) function. Regional peak systolic strain of the infarct segments and global longitudinal strain (GLS) after 3 months. At the acute phase, wall motion score index (WMSI), regional and global strain values were signficantly better in the viable than in the non viable segments. GLS was -10,92 ± 2,48 in patients with MRI non viable myocardium and -14,45 ±2,91 in patients with MRI viable myocardium . A pre-PCI strain value of -2,9% as a cutt off predicted segmental function recovery after PCI and myocardial viability with a sensitivity 82% of and a specificity 84%. Conclusion : This monocenter study confirms that 2D strain imaging can be a usueful and accurate method to predict myocardial viability and recovery of segmental and global LV function after PCI in STEMI patients.

P4626Neuronal nitric oxide sintetase polymorphism increases sympathetic activity and recurrent cardiovascular events after myocardial infarction

Abstract Background The expression and activity of neuronal nitric oxide sintetase (nNOS) in central and peripheral nervous system attenuate the sympathetic response and promote other cardioprotective effects in animal models. However, in humans those effects are uncertain. Recently, a polymorphism at the sequence rs41279104 G/T has been associated with a reduced expression of nNOS, but its clinical impact has never been studied in the context of ST elevation myocardial infarction (STEMI) in humans. Purpose We investigated the impact of the T allele at rs41279104 in sympathetic activation after STEMI and its influence in the incidence of recurrent major cardiovascular events (MACE). We sought to determine a pathway to autonomic nervous system modulation during STEMI and its possible clinical impact. Methods 297 patients were admitted in the first 24h (D1) after STEMI and followed prospectively. Blood samples and an electrocardiogram were obtained upon D1 and fifth day (D5). We assessed glycosylated hemoglobin, glucose, insulin, C-peptide, lipid profile and nitric oxide (NOx) plasma levels. We genotyped rs41279104 and grouped patients according to carrier status (GT+TT vs. GG). The heart rate variability was obtained with a 15min electrocardiogram recording and processed into spectral analysis variables including low (LF) and high frequencies (HF) and LF/HF ratio. Flow-mediated dilation (FMD) was performed after 30 days. Clinical follow–up was carried over until two years after MI and the endpoint was a composite of major cardiovascular events (MACE) consisting of fatal MI, non-fatal MI, unstable angina with hospitalization and cardiac sudden death. Results T-allele carriers showed a decreased parasympathetic activity and an increased sympathetic activity between D1 and D5 (ΔLF −68.43 (median) [IQR −324.76 to −6.29] vs −4.49 [−190.29 to 72.03], p&lt;0.001; ΔHF −19.40 [−185.55 to 6.21] vs −10.73 [−79.53 to 137.53], p=0.004; ΔLF/HF 0.07 [−2.32 to 1.44] vs −0.11 [−1.14 to 0.96], p&lt;0.001). Decreased FMD (6.9±4.7 vs 7.5±4.9, p=0.046) was also detected among T-allele carriers. In the Cox -regression analysis adjusted by sex, age, betablocker use and mean simvastatin dose, T-allele carriers had a relative risk for MACE of 2.112 (95% CI: 1.133–3.938; p=0.019). Conclusions The presence of the T allele at nNOS gene rs41279104 sequence is associated with increased sympathetic tone at acute phase of STEMI and a higher incidence of recurrent MACE.

P2661Ventricular fibrillation during acute STEMI is not associated with early repolarization pattern on ECG recorded prior to the index ischemic episode

Abstract Background Generally considered as benign, ECG early repolarization (ER) pattern was recently claimed to be an indicator of increased susceptibility to fatal arrhythmias during acute ischemia. The victims of sudden cardiac death have been reported to have high prevalence of ER comparing with survivors of acute coronary event. We aimed to test the association between the ER pattern on resting ECG recorded prior to ST-elevation myocardial infarction (STEMI) and the risk of ventricular fibrillation (VF) during acute phase of STEMI in non-selected population of STEMI patients. Methods For STEMI patients admitted to a tertiary care hospital for primary PCI during 2007–2010 (n=2286), all ECGs recorded prior to the date of admission with STEMI were extracted from a digital archive. The latest ECG recorded prior to the index STEMI was used for analysis. After excluding ECGs with paced rhythm and intraventricular blocks with QRS duration ≥120ms, the remaining ECGs were processed using the Glasgow algorithm allowing automatic ER detection. The association between ER-pattern on historical ECG and VF during the first 48 hours of STEMI was tested using logistic regression. Results Historical ECGs were available for 1584 patients; 124 of them were excluded due to a paced rhythm or wide QRS, leaving 1460 patients available for analysis (age 68±12 years, 67% male). The time from historical ECG to STEMI was 16 (IQR 4–49) months. ER pattern was present on historical ECG in 272 of 1460 (18.6%) (ER+ group), among them in 90 (33%) – in inferior leads, in 116 (43%) – in lateral leads, in 66 (24%) – both in inferior and lateral leads. ER+ patients were younger both at the time of historical ECG (64±13 vs 66±19; p=0.041) and at the time of STEMI (67±12 vs 68±12; p=0.033), and had lower heart rate on historical ECG (68±12 vs 73±15; p&lt;0.001) than ER- patients. ER+ and ER- groups did not differ regarding clinical characteristics and conventional ECG measurements. The course of STEMI was complicated by VF in 106 patients (17 of them from ER+ group). The occurrence of VF during STEMI was not associated with ER-pattern on historical ECG (OR 0.875 95% CI 0.518–1.479; p=0.618). There was no association of ER pattern with VF before reperfusion (OR 0.54 95% CI 0.25–1.21; p=0.135) or reperfusion VF (OR 1.28 95% CI 0.55–3.01; p=0.569). No association was observed with regard to localization (inferior or lateral) of ER-pattern either. Conclusion In a non-selected population of STEMI patients the presence of ER-pattern on ECG recorded prior to the acute coronary event was not associated with VF during the first 48 hours of STEMI.

IgM antibodies against phosphorylcholine measured early after acute ST-elevation myocardial infarction in relation to atherosclerotic disease burden and long-term clinical outcome.

PurposeStudies have reported an association between low levels of natural immunoglobulin M antibodies against phosphorylcholine(IgM anti-PC) and worse prognosis in patients with coronary artery disease (CAD). The aims of the present study were, in patients with ST-elevation myocardial infarction (STEMI); 1) to compare serum levels of IgM anti-PC measured acutely and after 3 months; 2) to study an association between levels of IgM anti-PC and the severity ofCAD, and; 3) to investigate whether IgM anti-PC levels are associated with long-term clinical outcome.MethodsA total of 213 patients without known diabetes (median age 59 years) with a PCI treated STEMI were enrolled. IgM anti-PC was measured in-hospital and after 3 months. Median follow-up time was 6.5 years (all-cause mortality, non-fatal myocardial re-infarction, recurrent ischemia causing hospital admission, heart failure and stroke). The severity of CAD was evaluated by coronary angiograms and patients were classified as having single- or multi-vessel disease and by SYNTAX score (SXscore).ResultsIgM anti-PC levels were stable over time when measured acutely and after 3 months. Patients with multi-vessel disease and high SXscore had significantly lower levels of IgM anti-PC in the acute phase of STEMI. Low levels of IgM anti-PC (the 25 percentile) measured acutely were associated with a 2-fold increase in the odds of having multi-vessel disease (adjusted OR 2.28 (95% CI 1.17, 4.44), p = 0.016), but not with high SXscore (Crude OR 2.20 (95% CI 0.96, 5.07), p = 0.06). Fifty-three patients experienced a new clinical event during long-term follow-up. Low levels of IgM anti PC were not associated with worse prognosis, (crude HR 1.54 (0.87–2.76), p = 0.14).ConclusionSTEMI patients with multi-vessel disease or high SXscore had significantly lower levels of IgM anti-PC in the acute phase and low levels were associated with multi-vessel disease, but not with worse clinical outcome during long-term follow-up.

Changes in Coronary Plaque Composition in Patients With Acute Myocardial Infarction Treated With High-Intensity Statin Therapy (IBIS-4): A Serial Optical Coherence Tomography Study

ObjectivesThis study assessed changes in optical coherence tomography (OCT)-defined plaque composition in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin treatment. BackgroundOCT is a high-resolution modality capable of measuring plaque characteristics including fibrous cap thickness (FCT) and macrophage infiltration. There is limited in vivo evidence regarding the effects of statins on OCT-defined coronary atheroma composition and no evidence in the context of STEMI. MethodsIn the IBIS-4 (Integrated Biomarker Imaging Study-4), 103 patients underwent intravascular ultrasonography and OCT of 2 noninfarct-related coronary arteries in the acute phase of STEMI. Patients were treated with high-dose rosuvastatin for 13 months. Serial OCT imaging was available in 153 arteries from 83 patients. We measured FCT by using a semi-automated method. Co-primary endpoints consisted of the change in minimum FCT (measured in fibroatheromas) and change in macrophage line arc. ResultsAt 13 months, median low-density lipoprotein cholesterol had decreased from 128 mg/dl to 73.6 mg/dl. Minimum FCT, measured in 31 lesions from 27 patients, increased from 64.9 ± 19.9 μm to 87.9 ± 38.1 μm (p = 0.008). Macrophage line arc decreased from 9.6° ± 12.8° to 6.4° ± 9.6° (p < 0.0001). The secondary endpoint, mean lipid arc, decreased from 55.9° ± 37° to 43.5° ± 33.5°. In lesion-level analyses (n = 191), 9 of 13 thin-cap fibroatheromata (TCFAs) at baseline (69.2%) regressed to non-TCFA morphology, whereas 2 of 178 non-TCFA lesions (1.1%) progressed to TCFAs. ConclusionsIn this observational study, we found significant increase in minimum FCT, reduction in macrophage accumulation, and frequent regression of TCFAs to other plaque phenotypes in nonculprit lesions of patients with STEMI treated with high-intensity statin therapy.

Relationship between TRAIL and Left Ventricular Ejection Fraction in Patients with ST-Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention.

Background Apoptosis plays an important role in the myocardial injury after acute myocardial infarction and in the subsequent development of heart failure. Aim To clarify serum kinetics of apoptotic markers TRAIL and sFas and their relation to left ventricular ejection fraction (LVEF) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Methods In 101 patients with STEMI treated with pPCI, levels of TRAIL and sFas were measured in series of serum samples obtained during hospitalization and one month after STEMI. LVEF was assessed at admission and at one month. Major adverse cardiovascular events (MACE, i.e., death, re-MI, and hospitalization for heart failure and stroke) were analysed during a two-year followup. Results Serum level of TRAIL significantly decreased one day after pPCI (50.5pg/mL) compared to admission (56.7pg/mL), subsequently increased on day 2 after pPCI (58.8pg/mL), and reached its highest level at one month (70.3pg/mL). TRAIL levels on days 1 and 2 showed a significant inverse correlation with troponin and a significant positive correlation with LVEF at baseline. Moreover, TRAIL correlated significantly with LVEF one month after STEMI (day 1: r=0.402, p<0.001; day 2: r=0.542, p<0.001). On the contrary, sFas level was significantly lowest at admission (5073pg/mL), increased one day after pPCI (6370pg/mL), and decreased on day 2 (5548pg/mL). Significantly highest sFas level was marked at one month (7024pg/mL). sFas failed to correlate with LVEF at baseline or at one month. Both TRAIL and sFas showed no ability to predict improvement of LVEF one month after STEMI or a 2-year MACE (represented by 3.29%). Conclusion In STEMI treated with pPCI, TRAIL reaches its lowest serum concentration after reperfusion. Low TRAIL level is associated with worse LVEF in the acute phase of STEMI as well as one month after STEMI. Higher TRAIL level appears to be beneficial and thus TRAIL seems to represent a protective mediator of post-AMI injury.

Evaluation of circulating levels of CCN2/connective tissue growth factor in patients with ST-elevation myocardial infarction

CCN2/Connective tissue growth factor seems to be involved in development of cardiac hypertrophy and fibrosis, but a possible cardioprotective role in left ventricular (LV) remodelling following myocardial infarction has also been suggested. The main objectives of the study were therefore to investigate whether circulating CCN2 levels were associated with infarct size, LV function, adverse remodelling or clinical outcome in two cohorts of patients with ST-elevation myocardial infarction (STEMI). CCN2 was measured in 988 patients 18 hours after PCI and clinical events were recorded after 55 months in the BAMI cohort. In the POSTEMI trial, serial measurements of CCN2 were performed in 258 STEMI patients during index hospitalisation and cardiac magnetic resonance imaging was performed in the acute phase and after 4 months. Clinical events were also recorded. There were no significant associations between levels of CCN2 and infarct size, LV ejection fraction, changes in LV end-diastolic or end-systolic volume, myocardial salvage or microvascular obstruction. There were no significant associations between CCN2 levels and clinical events including mortality, in either of the study cohorts. In conclusion, circulating levels of CCN2 measured in the acute phase of STEMI were not associated with final infarct size, left ventricular function or new clinical events.

Algorithm for the automatic computation of the modified Anderson–Wilkins acuteness score of ischemia from the pre-hospital ECG in ST-segment elevation myocardial infarction

BackgroundThe acuteness score (based on the modified Anderson–Wilkins score) estimates the acuteness of ischemia based on ST-segment, Q-wave and T-wave measurements obtained from the electrocardiogram (ECG) in patients with ST Elevation Myocardial Infarction (STEMI). The score (range 1 (least acute) to 4 (most acute)) identifies patients with substantial myocardial salvage potential regardless of patient reported symptom duration. However, due to the complexity of the score, it is not used in clinical practice. Therefore, we aimed to develop a reliable algorithm that automatically computes the acuteness score. MethodsWe scored 50 pre-hospital ECGs from STEMI patients, manually and by the automated algorithm. We assessed the reliability test between the manual and automated algorithm by interclass correlation coefficient (ICC) and Bland–Altman plot. ResultsThe ICC was 0.84 (95% CI 0.72–0.91), P<0.0001. The mean difference between manual and automated acuteness score was 0.17±0.66. In only two cases, there was a major disagreement between the two scores. There was an excellent agreement between the scores for the remaining 48 ECGs, all within the upper (1.46) and lower (−1.12) limits of agreement. ConclusionIn conclusion, we have developed an automated algorithm for measurement of the modified Anderson–Wilkins ECG acuteness score from the pre-hospital ECG in STEMI patients. This automated algorithm is highly reliable, can be applied in daily practice for research purposes and may be implemented in commercial automated ECG analysis programs to achieve practical use for decision support in the acute phase of STEMI.

Digoxin and short term mortality after acute STEMI: Results from the MAGIC trial

BackgroundThe safety of digoxin has been a subject of debate for decades, most recently among patients with atrial fibrillation (AF). Digoxin has been used during the acute phase of ST elevation myocardial infarction (STEMI) complicated with AF or heart failure. Data about digoxin in this setting are scarce. HypothesisWe hypothesize that digoxin maybe associated with increased mortality when used during the acute phase of ST segment myocardial infarction. MethodsWe investigated the association between digoxin and mortality in patients enrolled in the MAGnesium In Coronaries (MAGIC) study, which evaluated the efficacy of early magnesium administration in STEMI. Multiple Cox proportional hazards models were examined to assess the aforementioned association after correction for clinical characteristics and comorbidities. ResultsAfter excluding 639 (10.3%) patients for missing data, we analyzed the remaining 5574 patients. There were 852 (15.3%) deaths during the one month follow-up and 170 (3.0%) patients on digoxin concomitantly, among which 42 patients (24.7%) died. There was a statistically significant association between digoxin and increased mortality in the unadjusted statistical analysis; however, this association disappeared after correction for clinical characteristics and comorbidities in the primary multivariable analysis (estimated hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.62–1.19, p=0.372) and in three additional multivariable analyses. ConclusionDigoxin use as a new or preexisting medication during the acute phase of STEMI in the MAGIC trial was not associated with a significant increase in mortality after correcting for clinical characteristics and comorbidities.