KIDNEY FUNCTION DURING THE MYOCARDIAL INFARCTION WITH RECURRENT EPISODES OF ISCHEMIA IN YOUNG AND MIDDLE-AGED MEN

Relevance. Changes in renal function and their significance in reinfarction and early postinfarction angina have not been insufficiently established. Aim. To evaluate renal function changes in men under 60 years old with recurrent myocardial infarction and early postinfarction angina to improve prevention and outcomes. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with recurrent myocardial infarction and/or early postinfarction angina - 110 patients; II - control, without it - 555 patients. A comparative assessment of renal function changes in first 48 hours (1) and the end of third week disease (2), also risk analysis of recurrent ischemia and poor outcome in selected groups were performed. Results. The study group was distinguished by high levels of creatinine1 (0.11±0.03 (mmol/l)), lower - glomerular filtration rate (74.2±20.6 (ml/min/1.73 m2)) from the control (0.10±0.02 (mmol/l) and 78.3±17.9 (ml/min/1.73 m2), respectively; p=0.04). In both groups, there was a deterioration in indicators (creatinine, I: 2.3%; II: 5.9%; glomerular filtration rate - I: -5.8 and -6.3%, respectively; p<0.0001) during the observation period. The risk of recurrent ischemia increases with creatinine1 levels≥0.11 mmol/l and a glomerular filtration rate1˂70 ml/min/1.73 m2. In the study group, the risk of poor outcome is high with normal renal function. In the control group, it increased at creatinine1 levels≥0.10 mmol/l, glomerular filtration rate1˂65 ml/min/1.73 m2. Conclusions. Patients with recurrent ischemia have higher creatinine levels than controls. In both groups, during the study, there was a slight increase in creatinine and a decrease in glomerular filtration rate. The above values of renal function indices should be used in the formation of groups at high risk of early recurrence of ischemia and poor outcomes, as well as for predictive modeling of these complications.

PERIPHERAL HEMODYNAMICS PECULIARITIES IN YOUNG AND MIDDLE-AGED MEN WITH A RECIDIVATING MYOCARDIAL INFARCTION

Relevance. Hemodynamics changes in recidivating myocardial infarction and early postinfarction angina are not well understood. In recent years, the frequency of these complications has been increasing. Aim. To evaluate peripheral hemodynamics changes in men under 60 years old with recurrent myocardial infarction and early postinfarction angina to improve prevention and outcomes. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with recurrent myocardial infarction - 102 patients; II - control, without it - 541 patients. A comparative assessment of hemodynamics changes in first 48 hours (1) and the end of third week disease (2), also risk analysis of recurrent ischemia and poor outcome in selected groups were performed. Results. The study group was distinguished by a high level of total peripheral resistance1 (2055.5±965.2 (dyn×sec×cm-5)) from the control (2055.5± 965.2 (dyn×sec×cm-5); p=0.02). In both groups, a decrease in the values of all indicators was noted (p<0.05). A more pronounced decrease in total peripheral resistance was found in the study group, and in the parameters of blood pressure and heart rate - in the control group. The values of total peripheral resistance1 ≥1600 dyne×sec×cm-5 were the markers of the risk of ischemia recurrence. Predictors of poor outcome are blood pressure levels1 (systolic <97; diastolic <70; mean <93.3 (mm Hg)); total peripheral resistance1 <1746.2 dyne×sec×cm-5 and heart rate (˃92 per min). Conclusions. Patients with recurrent ischemia are characterized by higher levels of total peripheral resistance in the first hours of myocardial infarction. For both groups, a decrease in all studied indicators is determined. The above values of hemodynamic parameters should be used in the formation of groups with a high risk of early recurrence of ischemia and an unfavorable outcome, as well as for prognostic modeling of these complications.

Abstract P569: Adherence to Preventive Therapy and Early Recurrent Cerebral Ischemia in Patients With Symptomatic Intracranial Atherosclerotic Disease: Analysis of the Myriad Study

Background: Intracranial atherosclerotic disease (IAD) is a common cause of stroke with high rate of early recurrence despite maximal medical therapy. We sought to determine adherence to secondary preventive therapy and its association with early recurrent ischemia in patients with symptomatic IAD. Methods: The Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study included patients with recent stroke or transient ischemic attack due to moderate-to-severe IAD. Although MyRIAD did not mandate treatment, patients were recommended to follow standard secondary preventive management including antiplatelet therapy, lipid-lowering medications, antihypertensives for blood pressure (BP) goal <140/90 mmHg, smoking cessation and regular physical activity. Patients underwent 6-8 weeks assessment for medication adherence, smoking status, and physical activity compliance. Adherence to preventive therapy was correlated with new infarcts in the affected vessel territory on brain MRI. Results: Eighty-nine out of 105 patients enrolled in MyRIAD completed 6-8 weeks clinical and brain MRI assessment (mean age 64 +/- 12 years; 57% men). During follow up, 99% were on antiplatelets, 89% on lipid-lowering medications, 81% on antihypertensives, 48% had systolic BP at goal, 79% had diastolic BP at goal, 93% were not active smokers, and 47% were compliant with physical activity. Overall, new infarcts on brain MRI were found in 25% patients. Although no significant differences were found, patients with uncontrolled BP, active smokers and those not compliant with physical activity had a higher frequency of new infarcts in the affected vessel territory (Table). Conclusions: Medication adherence was high after IAD-related stroke. However, a noteworthy fraction of patients had uncontrolled BP, continue to smoke, and were not compliant with physical activity. The latter may represent important therapeutic targets to prevent early recurrent ischemia.

Abstract 12899: Early Intervention in Transient ST-Elevation Myocardial Infarction Decreases Mortality: A Meta-Analysis

Introduction: About one-fourth of patient with acute coronary syndrome present with transient ST-elevation myocardial infarction (STEMI). No specific recommendations exist in current guidelines regarding the timing of intervention for such patients due to lack of high-quality randomized trials. Methods: The Cochrane library and PubMed databases were searched for relevant studies. Two authors independently screened and included studies that were randomized controlled trials or observational studies comparing early with delayed invasive strategies in transient STEMI. Efficacy outcomes included target vessel revascularization, reinfarction and recurrent ischemia rates. Primary safety outcome was major bleeding. Random-effects model was used for pooled calculation of odds ratio (OR). Results: Out of all studies found, only 4 studies were included in our analysis (295 patients in early intervention group and 307 patients in delayed intervention group). Delayed intervention was associated with significant increase in all-cause mortality (OR: 2.81 [1.39-5.68], I 2 = 0%, p value = 0.004) (Figure 1). We did not find any significant difference in reinfarction rate (OR: 0.75 [0.12-4.66], I 2 = 0%, p value = 0.75), target vessel revascularization rate (OR: 0.66 [0.11-4.14] I 2 = 0%, p value = 0.66) and recurrent ischemia rate (OR 1.52[0.40-5.84], I 2 = 18 %, p value = 0.54). In addition, major bleeding rate was also similar in both groups (OR 0.68 [0.25-2.25], I 2 = 12%, p value = 0.60). Conclusions: This low to moderate-quality evidence suggests that early invasive strategy might reduce the mortality rate in transient STEMI. There is need of well-designed large randomized studies to gather further evidence regarding the best management of transient STEMI.

A REVIEW ON MANAGEMENT PRINCIPLES AND MEDICATION OF MYOCARDIAL INFARCTION

Myocardial infarction is the most common public health issue and a major cause of death including disorders of heart and blood vessels. Among all heart problems, ventricular fibrillation is the major cause that occurs soon after the onset of ischemia. As the patient reaches hospital major aim is to decrease the size of the infarct. The control and management of MI depend on the pathophysiological conditions and the time course of irreversible myocardial injury. The fundamental goals of managing acute MI include: (i) Duration of exposure of myocardium to ischemia should be minimized. (ii) Rapid reperfusion (iii) Preventing recurrent ischemia and re-occlusion. (iv) Managing cardiac arrhythmia and other mechanical complications. Management of MI requires prompt diagnosis and therapy including Fibrinolytic therapy, Antithrombin agents, Antihypertensive, and currently discovered many kinds of drugs including LCZ696 and new FDA- Approved treatment and therapies.

P1696Clinical value of QRS spatial dispersion in non-ST elevation myocardial infarction

Background More than 40% of patients with non-ST Elevation Myocardial Infarction (NSTEMI) have multi-vessel disease with the rate of in-hospital emergent bypass surgery ranging from 11–13%. So, rapid scoring is critical for optimum management even before P2Y12 loading. Purpose We aimed to determine the role of QRS dispersion at emergency department, as a simple and rapid sign, in predicting coronary anatomy complexity and in-hospital outcome. Methods 192 (126 males, age 57.4±6.8 years) patients with NSTEMI and QRS duration <120 ms who underwent coronary angiography were included. QRS dispersion was automatically measured. Results Using Spearman's rank correlation, SYNTAX score was found to be positively correlated with admission HR (r 0.54, p value <0.001), maximum HsTnT level (r 0.523, p value <0.001), age (r 0.262, p value 0.015), male gender (r 0.286, p value 0.005), QRS dispersion (r 0.248, p value 0.015), QTc dispersion (r 0.289, p value 0.01), and Grace score (r 0.247, p value 0.015). ROC curve analyses for prediction of SYNTAX score >33 were done for variables with significant correlation. By multivariate logistic regression, male gender (OR 5.042, 95% CI 1.633 –15.567, p value 0.005), admission HR >80 bpm (OR 1.088, 95% CI 1.024 –1.157, p value 0.017) and QRS dispersion >20ms (OR 1.020, 95% CI 1.003 –1.037, p value 0.02) were independent predictors of SYNTAX score >33 (table). Patients with QRS dispersion >20 ms had in-hospital higher Killip class (P<0.001), recurrent ischemia (P 0.003), serious ventricular arrhythmias (P 0.01) and higher GRACE score (P<0.001). Binary logistic regression for prediction of SYNTAX score >33 Variables Univariate analysis Multivariate analysis OR (95% CI) P value OR (95% CI) P value Age >61 (years) 1.337 (1.019–4.392) 0.015 0.953 (0.878–1.033) 0.242 Male gender 4.851 (2.014–5.301) 0.001 5.042 (1.633–15.567) 0.005 HR >80 (bpm) 3.945 (1.706–6.953) 0.002 1.088 (1.024–1.157) 0.017 QRS dispersion >20 (ms) 2.911 (0.617–13.738) 0.013 1.020 (1.003–1.037) 0.02 QTc dispersion >53 (ms) 6.101 (1.926–19.323) 0.002 2.378 (1.890–2.561) 0.043 Maximum HsTnT >1105 (ng/L) 3.837 (0.236–8.965) 0.004 2.785 (2.501–3.012) 0.034 Grace Score >112 (points) 7.122 (0.632–12.216) <0.001 2.912 (2.703–3.309) 0.030 Conclusion In NSTEMI, QRS dispersion was positively correlated with SYNTAX score and a cut-off value of 20 ms independently predicted SYNTAX score >33. Regarding in-hospital outcome, QRS dispersion >20 ms was associated with in-hospital higher Killip class, recurrent ischemia, serious ventricular arrhythmias and higher GRACE score

Neutrophil Extracellular Traps Promote Hypercoagulability in ST-Elevated Myocardial Infarction Following Fibrinolytic Administration

Introduction:Fibrinolysis plays an important role in the treatment of ST-elevated myocardial infarction (STEMI) when percutaneous coronary intervention is not readily available. Early and successful myocardial reperfusion with thrombolytic therapy effectively reduces the infarct size and improves the clinical outcome. However, the process of restoring blood flow to the ischemic myocardium can induce injury and reduce the beneficial effects of myocardial reperfusion. Previous studies had shown that platelets, leukocytes and TF play important role in thrombotic complications after fibrinolysis in AMI. However, there are still 10-15% patients who have risk for re-occlusion after antiplatelet and anticoagulant therapies. Thus, we speculate that there may be other mechanisms involved in the hypercoagulability after STEMI fibrinolysis. Neutrophil extracellular traps (NETs) are double-edge swords that could ensnare and kill microbial pathogens but also contribute to thrombosis. However, the role of NETs during STEMI fibrinolysis-induced re-occlusion is largely unknown. Our aims were to determine the procoagulant role of NETs after successful thrombolysis, and to elucidate its interaction with endothelial cells (ECs). Methods:31 STEMI patients with successfully fibrinolysis and 12 healthy controls were enrolled. Patient blood samples were collected at 0 h, 2 h, 6 h, 12 h and 24 h after fibrinolysis. Cell-free DNA (cf-DNA) was quantified using the Quant-iT PicoGreen dsDNA Assay Kit. ELISA was used to detect MPO-DNA complexes and TAT (thrombin-antithrombin) complexes. Wright-Giemsa and immunofluorescence confocal microscope were used to analyze and quantify NETs formation in neutrophil cells. ECs were incubated in growth media containing 20% pooled serum obtained from healthy donors in the presence or absence of 20-fold concentrated neutrophil extracellular chromatin. The procoagulant activity (PCA) of neutrophils and ECs was measured by clotting time and purified coagulation complex assays. DNase I or anti-TF were included in the inhibition assays. Results: We found that cf-DNA, MPO-DNA and TAT are significantly reduced at 2 hours in STEMI patients with successful fibrinolysis. Their levels then increased and peaked at 6 hours (Figure 1A, B, E). Interestingly, the level of cf-DNA at 6 hours in STEMI thrombotic patients was positively correlated with TAT (r=0.959; p<0.01; Figure 1G). Wright-Giemsa and immunofluorescence staining showed that NETs were released by STEMI reperfusion neutrophils or by control neutrophils treated with plasma obtained from STEMI patients with fibrinolysis (Figure 1D,F), and the percentage of NETs-releasing PMNs was about 30% (Figure 1C). Isolated neutrophils from fibrinolytic patients in vitro demonstrated significantly shortened coagulation time and increased fibrin formation after 2 hours fibrinolysis, and peaked at 6 hours. DNase I but not anti-tissue factor antibody could inhibit these effects. Co-incubation assays revealed that NETs triggered PS exposure on ECs, converting them to a procoagulant phenotype. Confocal imaging of NETs-treated ECs illustrated that bound FVa and FXa colocalized within PS-enriched areas of ECs to form prothrombinase, and further supported fibrin formation. Moreover, patients with recurrent ischemia showed significantly higher NETs release and thrombin generation than non-recurrent ischemia. Conclusions: Our study reveals that the PCA of STEMI following fibrinolytic administration decrease after 2 hours, then increase and peak at 6 hours, which is at least partly due to the release of NETs induced by activated PMNs. Additionally, NETs partly contribute to ECs injury after myocardial reperfusion. DNase I can disconnect NETs and may therefore serve as a promising therapeutic target in STEMI reinfarction and recurrent ischemia. Disclosures No relevant conflicts of interest to declare.