Adjunctive Reperfusion Therapy Post-AMI

Author(s):  
Thorsten Reffelmann ◽  
Robert Kloner

• Reperfusion of the occluded coronary artery in an ST-segment-elevation myocardial infarction is the most effective approach for reducing infarct size, preserving left ventricular ejection fraction, lowering the incidence and severity of congestive heart failure and improving prognosis• Hence, several pharmacologic agents intended to improve target vessel patency as an adjunct to thrombolysis or primary percutaneous coronary intervention have been shown to be beneficial in patients with reperfusion therapy for acute myocardial infarction, namely antiplatelet and anticoagulation agents• Animal investigations have suggested that coronary reperfusion may also result in undesirable cardiac alterations, termed ‘reperfusion injury’, such as reversible contractile dysfunction (‘stunning’), microvascular obstruction (‘no-reflow’), and in several studies the progression of myocardial necrosis (‘lethal reperfusion injury’)• Clinical investigations of various pharmacologic interventions as an adjunctive therapy to reperfusion to reduce final infarct size, the amount of contractile dysfunction and to improve prognosis have been mostly inconsistent; only a few interventions, e.g. adenosine and atrial natriuretic peptide seem to show promise at least in certain subgroups.

2017 ◽  
Vol 22 (6) ◽  
pp. 538-545 ◽  
Author(s):  
Daniel Medeiros Moreira ◽  
Maria Emilia Lueneberg ◽  
Roberto Leo da Silva ◽  
Tammuz Fattah ◽  
Carlos Antonio Mascia Gottschall

Purpose: Methotrexate is an anti-inflammatory drug that has been shown to have anti-ischemic effects. Our aim was to evaluate if methotrexate could reduce infarct size in patients with ST-segment elevation myocardial infarction (STEMI). Methods: We randomly assigned patients with STEMI to receive either methotrexate or placebo. Primary outcome was infarct size determined by calculating the area under the curve (AUC) for creatine kinase (CK) release. Secondary outcomes were AUC of CK MB (CK-MB) and AUC of troponin I; peak CK, peak CK-MB, and troponin I; B-type natriuretic peptide (BNP) level, high-sensitivity C-reactive protein (hsCRP) result, and erythrocyte sedimentation rate (ESR); left ventricular ejection fraction (LVEF); thrombolysis in myocardial infarction (TIMI) frame count; Killip score; mortality and reinfarction incidence; and incidence of adverse reactions. Results: We included 84 patients. Median AUC of CK was 78 861.0 in the methotrexate group and 68 088.0 in the placebo group ( P = .10). Patients given methotrexate and placebo exhibited, respectively, median AUC for CK-MB of 9803.4 and 8037.0 ( P = .42); median AUC for troponin of 3691.1 and 2132.6 ( P = .09); peak CK of 2806.0 and 2147.0 ( P = .05); peak CK-MB of 516.0 and 462.3 ( P = .25); and peak troponin of 121.0 and 85.1 ( P = .06). At 3 months, LVEF was lower in patients who received methotrexate (49.0% ± 14.1%) than in patients given placebo (56.4% ± 10.0%; P = .01). There were no differences in hsCRP, ESR, BNP, Killip scores, TIMI frame count, reinfarction, and mortality rates. There was a higher median serum glutamic–pyruvic transaminase levels in the methotrexate group. Conclusion: Methotrexate did not reduce infarction size and worsened LVEF at 3 months ( Clinicaltrials.gov identifier NCT01741558).


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Demirkiran ◽  
N Hoeven ◽  
G Janssens ◽  
J Lemkes ◽  
H Everaars ◽  
...  

Abstract Background Up to one out of four patients with signs of ST-segment elevation myocardial infarction (STEMI) express complete normalization of ST elevation before primary revascularization procedure. This condition is commonly referred to as “transient ST-segment elevation myocardial infarction” (TSTEMI) and recent data suggests that this group of patients may have favorable outcome compared to STEMI patients. However, it is currently unknown how these patients compare to both STEMI and non-ST-segment elevation myocardial infarction (NSTEMI) patients with respect to infarct size characteristics and outcome. Objective This study aims to explore cardiac magnetic resonance (CMR) derived scar tissue and 1-year outcome in patients with TSTEMI by comparison to STEMI and NSTEMI. Methods Patients with STEMI were enrolled from two prospective studies (n=170); the patients with TSTEMI were recruited from the TRANSIENT trial (n=141); the patients with NSTEMI were prospectively and consecutively collected from local registries of Amsterdam UMC (n=57) and Maastricht UMC (n=51). All patients underwent CMR examination 2–8 days after the index event. Cine imaging was done for volume and function assessment. Late gadolinium enhancement imaging was performed to identify infarct size (in grams) and the presence of microvascular obstruction (MVO). All CMR images were processed in a single core laboratory (Amsterdam UMC). Clinical outcome after 1 year was measured by the incidence of major adverse cardiac events (MACE), defined as recurrent myocardial infarction (MI), revascularization and all cause death. Results The TSTEMI group demonstrated the lowest end-systolic left ventricular volume and highest left ventricular ejection fraction across the groups (overall p<0.001). Although there was a remarkably lower infarct size in TSTEMI patients compared to STEMI (1.41g [0.00–3.91] vs 13.48g [5.31–26.81], p<0.001), there was only a trend towards lower infarct size compared to NSTEMI patients (1.41g [0.00–3.91] vs 2.13g [0.00–8.64], p=0.06). Whilst MVO was observed less frequently in TSTEMI compared to STEMI patients (5 (4%) vs 53 (31%), p<0.001), no significant difference was seen between TSTEMI and NSTEMI patients (5 (4%) vs 5 (5%), p=0.72). Multivariable linear regression analysis identified infarct type, smoking, peak troponin-T and pre-PCI TIMI flow as predictors for infarct size (p=0.03, p=0.03, p<0.001 and p<0.001, respectively). One-year mortality rate was low in all 3 MI types (TSTEMI 3 (2.2%), NSTEMI 3 (3.1%), 4 (2.4%), log-rank test p=0.91). However, there was a significant difference in MACE at 1 year across the 3 MI types (TSTEMI 18 (13.2%), NSTEMI 19 (19.4%), STEMI 11 (6.7%), overall p<0.01). Conclusion In comparison to NSTEMI and STEMI, TSTEMI yielded favorable cardiac left ventricular function and scar mass. However, this did not lead to benefit in short term (1-year) outcome; further studies are needed with longer follow-up. Funding Acknowledgement Type of funding source: Other. Main funding source(s): European Association of Cardiovascular Imaging (EACVI) Research Grant


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Marcos Garces ◽  
C Rios-Navarro ◽  
L Hueso ◽  
A Diaz ◽  
C Bonanad ◽  
...  

Abstract Background Angiogenesis participates in re-establishing microcirculation after myocardial infarction (MI). Purpose In this study, we aim to further understand the role of the anti-angiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and explore its potential as a co-adjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: 1) permanent coronary ligation (non-reperfused MI), 2) transient 45-min coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. Serum and myocardial VEGF-A165b levels were determined. In both experimental MI models, functional and structural implication of VEGF-A165b blockade was assessed. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6-months and with the occurrence of adverse events (death, heart failure and/or re-infarction). Results In both models, circulating and myocardial VEGF-A165b presence was increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockage increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in non-reperfused MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. Conclusions In experimental and clinical studies, higher serum VEGF-A165b levels associates with a worse systolic function. Its blockage enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in non-reperfused MI experiments. Therefore, VEGF-A165b neutralization represents a potential co-adjuvant therapy to coronary reperfusion. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (Exp. PIE15/00013, PI17/01836, PI18/00209 and CIBERCV16/11/00486).


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuai Meng ◽  
Yong Zhu ◽  
Kesen Liu ◽  
Ruofei Jia ◽  
Jing Nan ◽  
...  

Abstract Background Left ventricular negative remodelling after ST-segment elevation myocardial infarction (STEMI) is considered as the major cause for the poor prognosis. But the predisposing factors and potential mechanisms of left ventricular negative remodelling after STEMI remain not fully understood. The present research mainly assessed the association between the stress hyperglycaemia ratio (SHR) and left ventricular negative remodelling. Methods We recruited 127 first-time, anterior, and acute STEMI patients in the present study. All enrolled patients were divided into 2 subgroups equally according to the median value of SHR level (1.191). Echocardiography was conducted within 24 h after admission and 6 months post-STEMI to measure left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD). Changes in echocardiography parameters (δLVEF, δLVEDD, δLVESD) were calculated as LVEF, LVEDD, and LVESD at 6 months after infarction minus baseline LVEF, LVEDD and LVESD, respectively. Results In the present study, the mean SHR was 1.22 ± 0.25 and there was significant difference in SHR between the 2 subgroups (1.05 (0.95, 1.11) vs 1.39 (1.28, 1.50), p < 0.0001). The global LVEF at 6 months post-STEMI was significantly higher in the low SHR group than the high SHR group (59.37 ± 7.33 vs 54.03 ± 9.64, p  = 0.001). Additionally, the global LVEDD (49.84 ± 5.10 vs 51.81 ± 5.60, p  = 0.040) and LVESD (33.27 ± 5.03 vs 35.38 ± 6.05, p  = 0.035) at 6 months after STEMI were lower in the low SHR group. Most importantly, after adjusting through multivariable linear regression analysis, SHR remained associated with δLVEF (beta = −9.825, 95% CI −15.168 to −4.481, p  < 0.0001), δLVEDD (beta = 4.879, 95% CI 1.725 to 8.069, p  = 0.003), and δLVESD (beta = 5.079, 95% CI 1.421 to 8.738, p  = 0.007). Conclusions In the present research, we demonstrated for the first time that SHR is significantly correlated with left ventricular negative remodelling after STEMI.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Osokina ◽  
V.N Karetnikova ◽  
O.M Polikutina ◽  
Y.S Slepynina ◽  
T.P Artemova ◽  
...  

Abstract Objective To investigate the correlation between Procollagen I C-Terminal Propeptide (PICP), Procollagen III N-Terminal Propeptide (PIIINP), indices of echocardiography and anamnestic data in patients with ST segment elevation myocardial infarction (STEMI) and preserved myocardial contractility. Materials and methods 60 men and 23 women diagnosed with STEMI were examined. Echocardiographic studies were performed using SONOS 2500 Cardiac – Vascular Ultrasound (Hewlett Packard, USA). Myocardial contractility was considered to be preserved with left ventricular ejection fraction (LVEF) ≥50%. In addition to standard indices of echocardiography, mitral flow propagation velocity (FPV) was evaluated to diagnose diastolic dysfunction. Coronary angiography was performed using INNOVA 3100 Cardiovascular Imaging System (USA). All patients, during the first twelve hours of the disease, underwent percutaneous coronary intervention (PCI) with stenting of the occluded culprit infarct-related artery. On the 1st and 12th days of hospitalization, the concentrations of PICP and PIIINP were determined for all patients by enzyme-linked immunosorbent assay (ELISA) using laboratory BCM Diagnostics kits (USA). All patients at the hospital received standard therapy. Results The following marker values were obtained: 1st day: PICP 609 (583; 635) ng/ml, PIIINP 26 (18.9; 34.9) ng/ml; 12th day: PICP 588 (580; 561) ng/ml, PIIINP 24.2 (18.6; 30.3) ng/ml. The following significant correlations were revealed: PICP 1st day / isovolumic contraction time – IVCT (m/s) 12th day, r=−0.68, p=0.042; PICP 1st day / Tei Index 12th day, r=−0.72, p=0.028; PICP 1st day / diastolic rigidity 12th day, r=−0.74, p=0.021; PIIINP 1st day/age, r=0.55, p=0.016; PIIINP 1st day/ body mass index (BMI), r=−0.59, p=0.009; PIIINP 1st day / E (cm/s) 1st day, r=0.72, p=0.018; PIIINP 1st day / Em /FPV 1st day, r=0.78, p=0.007; PIIINP 12th day / Em / FPV 1st day, r=0.65, p=0.041; PIIINP 12th day / E (cm/s) 1st day, r=0.67, p=0.033; PIIINP 12th day / E / Em) 12th day, r=0.70, p=0.023; PIIINP 12th day / Em/FPV 12th day, r=0.73, p=0.014. Conclusions The data obtained indicates the correlation between serum markers of myocardial fibrosis and the indices of echocardiography, as well as age. We conclude that, all the markers listed above, are able to represent myocardial remodeling in patients with STEMI. Funding Acknowledgement Type of funding source: None


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yumei Ye ◽  
Jose R Perez-Polo ◽  
Manjyot K Nanhwan ◽  
Sven Nylander ◽  
Yochai Birnbaum

Background: Clopidogrel (C) and Ticagrelor (T) are P2Y12 ADP receptor antagonists. In addition, ticagrelor inhibits adenosine cell uptake. In PLATO trial T reduced the incidence of the primary composite endpoint myocardial infarction, stroke or cardiovascular death over C in patients with acute coronary syndromes. Previous data show that 7d pretreatment with T limits infarct size (IS) in rats. We compared the effects of C and T, administered just before reperfusion on IS. We also assessed the effect of T and C, administered just before reperfusion and/or 6w oral treatment on cardiac remodeling. Methods: Rats underwent 30min coronary artery ligation. 1) At 25min of ischemia rats received intraperitoneal (IP) vehicle, T (10 or 30mg/kg), or C (12.5mg/kg). Area at risk (AR) was assessed by blue dye and IS by TTC staining 24h after reperfusion. 2) Rats received vehicle without (sham) or with (control) coronary ischemia, T (30mg/kg) IP (TIP), T (300mg/kg/d) oral for 6w, started a day after reperfusion (TPO), TIP+PO (TIPPO), or C (12.5mg/kg IP +62.5mg/kg/d PO for 6w). LV dimensions and function was assessed by echo at 6w. Results: 1) AR was comparable among groups. IS was 45.3±1.7% of the AR in the control group. T10 (31.5±1.8%; p=0.001) and T30 (21.4±2.6% p<0.001) significantly reduced IS, whereas C (42.4±2.6%) had no effect. Platelet aggregation in the controls was 64.7±1.3% and was comparable in T30 (24.9±1.8%) and C (23.2±1.8%) at 2h post reperfusion. T30 increased Akt, eNOS and ER1/2 phosphorylation 4h after reperfusion, whereas C had no effect. 2) Platelet aggregation at 1w oral treatment was 59.7±3.2% in the control group and was comparable in TIPPO (18.1±1.3%) and C (17.4±0.7%). Left ventricular ejection fraction was 77.6±0.9%*, 44.8±3.5%, 69.5±1.6%*, 69.2±1.0%*, 76.3±1.2%*, and 37.4±3.7% in the sham, vehicle, TIP, TPO, TIPPO and C treated group, respectively (*p<0.001 vs. vehicle). Left ventricular diameters at diastole and systole showed the same pattern. Conclusions: T, but not C, administered just before reperfusion protects against reperfusion injury. Oral T (in combination or not with acute treatment just before reperfusion) treatment for 6w improves heart function. C, despite achieving similar degree of platelet inhibition had no effect on remodeling.


2021 ◽  
Vol 10 (23) ◽  
pp. 5677
Author(s):  
Mohammad A. Almesned ◽  
Femke M. Prins ◽  
Erik Lipšic ◽  
Margery A. Connelly ◽  
Erwin Garcia ◽  
...  

The gut metabolite trimethylamine N-oxide (TMAO) at admission has a prognostic value in ST-elevation myocardial infarction (STEMI) patients. However, its sequential changes and relationship with long-term infarct-related outcomes after primary percutaneous coronary intervention (PCI) remain elusive. We delineated the temporal course of TMAO and its relationship with infarct size and left ventricular ejection fraction (LVEF) post-PCI, adjusting for the estimated glomerular filtration rate (eGFR). We measured TMAO levels at admission, 24 h and 4 months post-PCI in 379 STEMI patients. Infarct size and LVEF were determined by cardiac magnetic resonance 4 months after PCI. TMAO levels decreased from admission (4.13 ± 4.37 μM) to 24 h (3.41 ± 5.84 μM, p = 0.001) and increased from 24 h to 4 months (3.70 ± 3.86 μM, p = 0.026). Higher TMAO values at 24 h were correlated to smaller infarct sizes (rho = −0.16, p = 0.024). Larger declines between admission and 4 months suggestively correlated with smaller infarct size, and larger TMAO increases between 24 h and 4 months were associated with larger infarct size (rho = −0.19, p = 0.008 and rho = −0.18, p = 0.019, respectively). Upon eGFR stratification using 90 mL/min/1.73 m2 as a cut-off, significant associations between TMAO and infarct size were only noted in subjects with impaired renal function. In conclusion, TMAO levels in post-PCI STEMI patients are prone to fluctuations, and these fluctuations could be prognostic for infarct size, particularly in patients with impaired renal function.


Angiology ◽  
2020 ◽  
Vol 71 (9) ◽  
pp. 799-803
Author(s):  
Mehmet Kucukosmanoglu ◽  
Yahya Kemal İçen ◽  
Hilmi Erdem Sumbul ◽  
Hasan Koca ◽  
Mevlut Koc

The purpose of this study is to investigate the relation between residual SYNTAX score (rSS) and contrast-induced nephropathy (CIN) development in patients with non-ST segment elevation myocardial infarction (NSTEMI) with normal or near-to-normal left ventricular ejection fraction (LVEF) who underwent percutaneous coronary intervention (PCI). A total of 306 patients who underwent PCI with NSTEMI were included in our study. SYNTAX scores were calculated for the periods before and after PCI. Patients were divided into 2 groups as developed CIN following PCI (CIN +) and patients did not (CIN −). Fifty-four (17.6%) of patients who were included in the study developed CIN. Age ( P = .001) and rSS ( P = .002) were significantly higher and LVEF was lower ( P = .034) in the CIN (+) group. Age ( P = .031, odds ratio [OR]: 1.031, 95% CI, 1.003-1.059) and rSS ( P = .04, OR: 1.036, 95% CI, 1.002-1.071) were independent predictors for CIN. In receiver operating characteristic analyses, when the cutoff value of rSS was taken as 3.5, it determined CIN with 79% sensitivity and 65% specificity. Contrast-induced nephropathy may develop more frequently in patients with increased rSS value. The rSS may be useful to follow-up these patients for CIN development.


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