Myocardial gene expression in patients with myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction. Myocardial infarction (MI) and following heart failure (HF) have various clinical scenarios. However, despite the clinical heterogeneity, the management of MI lacks effective personalized approaches. The response to ischemic injury in the infarct zone and remote myocardium has a definite spatio-temporal sequence and underlies the mechanism of adverse cardiac remodeling. Understanding its myocardial biology remains unclear due to insufficiency of heart tissue molecular and genetic analysis. Although animal models play an important role in data accumulation, they failure to reflect all the compounds of response to ischemic injury and following HF syndrome. Purpose. The purpose of the study was to investigate myocardial expression profile in the infarct zone in comparison to remote myocardium in patients with MI. Methods. The study included 4 patients with fatal MI type 1. All patients died within 48 hours of MI. The post-mortem examination was performed according to country policy. In each case, we obtained myocardial samples from the infarct zone and remote myocardium. Genome-wide gene-level expression was assessed by microarray analysis. We used transcriptome analysis software to analyze and visualize global expression patterns of genes. The analysis included normalization process. Differentially expressed genes (DEGs) were defined as gene-level fold change <-2 or >2 and adjusted P-value of <0.05. Results. We studied expression of 21448 genes. A total of 1785 DEGs, including 1692 up-regulated genes and 93 down-regulated genes in the infarct zone, were identified (Figure 1). According to the fold change, the first 10 up-regulated genes were TNFSF10 (TRAIL), SUCLA2, NAE1, PDCL3, OSBPL5, FCGR2C, SELE, CEP63, ST3GAL3, C4orf3. Fold changes for TNFSF10 (TRAIL), SUCLA2, and NAE1 were 19.83 (p = 0.049), 10.68 (p = 0.048), and 10.24 (p = 0.008), respectively. These 3 up-regulated genes were enriched in apoptotic signaling pathways, immune response, angiogenesis, inflammation, tricarboxylic acid cycle, and protein binding. Conclusions. We performed myocardial transcriptomic analysis in patients with MI. DEG analysis clearly distinguishes the infarct zone and remote myocardium. Genes overexpressed in the infarct zone included TNFSF10 (TRAIL), SUCLA2, NAE1. TNFSF10 (TRAIL) regulates vasodilation, angiogenesis, and inflammation. TNFSF10 (TRAIL) regulated effects could be both protective and harmful in ischemic heart disease. The enzyme encoded by SUCLA2 is active in tissues that require a large amount of energy, such as those of the heart, brain, and muscle. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation. It is known that the protein encoded by NAE1 binds to the beta-amyloid precursor protein, and it is thought to play a role in the pathogenesis of Alzheimer"s disease. Thus, our pilot study emphasized the potential of translational approach and identified targets to consider for precision diagnostics and therapeutics. Abstract Figure. С1: infarct zone; C2: remote myocardium

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Assessment of Admission Time Cell Blood Count (CBC) Parameters in Predicting Post-primary Percutaneous Coronary Intervention TIMI Frame Count in Patients with ST-segment Elevation Myocardial Infarction

Cardiovascular & Haematological Disorders - Drug Targets ◽

10.2174/1871529x20666200206123118 ◽

2020 ◽

Vol 20 (3) ◽

pp. 191-197

Author(s):

Hossein Vakili ◽

Isa Khaheshi ◽

Amirsina Sharifi ◽

Negin Nickdoost ◽

Mohammad H. Namazi ◽

...

Keyword(s):

Myocardial Infarction ◽

Platelet Count ◽

P Value ◽

Primary Pci ◽

Blood Samples ◽

Timi Frame Count ◽

Admission Time ◽

No Reflow ◽

Corrected Timi Frame Count ◽

No Reflow Phenomenon

Objectives: In this study, we aimed to assess the value of admission time CBC parameters in predicting post-primary PCI corrected TIMI frame count. Background: Recent years have witnessed a large series of studies evaluating different laboratory variables to predict no-reflow phenomenon following primary PCI (PPCI) in patients with STEMI. However, a general agreement about the most reliable predictor of the no-reflow phenomenon is challenging and also intriguing. Methods: The current study concluded 208 consecutive patients who underwent primary PCI for ST-Elevation Myocardial Infarction (STEMI) from January 2014 to February 2016. Blood samples were obtained after taking ECG. Complete blood samples were collected and analyzed within 5 minutes from sampling. Post-PCI corrected Thrombolysis in Myocardial Infarction (TIMI) frame count was determined by one interventional cardiologist blinded to patients’ clinical data. The correlation between admission time blood parameters and post-primary PCI corrected TIMI frame count in patients with STEMI were assessed. Results: Corrected TIMI frame count was positively correlated with WBC count (R: 0.18, P-value: <0.01), neutrophil count (R: 0.34, P-value: <0.01), and platelet count (R: 0.23, P-value: <0.01) and negatively correlated with lymphocyte count (R: -0.2, P-value: <0.01). Multiple linear regression results demonstrated that corrected TIMI frame count was positively correlated with neutrophil count (P < 0·001) and platelet count (P < 0·001) and negatively correlated with lymphocyte count (p=0.004). Conclusion: High counts of WBC, neutrophil, and platelet and low count of lymphocyte may be predictors of no-reflow in STEMI patients undergoing PPCI. The clinical significance of such predictive parameters becomes clear as we consider the treatment approach in STEMI patients. Appropriate risk stratification leads to better treatment planning and allocation of resources.

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P5525Impact of clinical presentation at admission on long-term clinical outcomes in patients undergoing percutaneous coronary interventions - a contemporary registry data

European Heart Journal ◽

10.1093/eurheartj/ehz746.0473 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

L Piatek ◽

L Zandecki ◽

J Kurzawski ◽

A Janion-Sadowska ◽

M Zabojszcz ◽

...

Keyword(s):

Myocardial Infarction ◽

Unstable Angina ◽

Stable Angina ◽

Clinical Presentation ◽

P Value ◽

Cardiac Events ◽

St Segment Elevation ◽

St Segment ◽

Adverse Cardiac Events ◽

Percutaneous Coronary

Abstract Background Both unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) are still classified together in non-ST-elevation acute coronary syndromes despite the fact they substantially differ in both clinical profile and prognosis. Purpose The aim of the present study was to evaluate contemporary clinical characteristics and outcomes of UA patients after percutaneous coronary intervention (PCI) in comparison with stable angina (SCAD) and myocardial infarction (NSTEMI as well as STEMI) in Swietokrzyskie District of Poland in years 2014–2017. Methods A total of 7'187 patients after PCI from ORPKI Registry (38% with diagnosis of UA) were included into the analysis. Impact of clinical presentation (UA, SCAD, NSTEMI, STEMI) on 3-year outcomes were determined. Results UA patients were older that SCAD but younger than NSTEMI individuals. Diabetes and hypertension were more often encountered into UA group than in NSTEMI but less often than in SCAD cases. In UA group the percentage of previous myocardial infarction (MI), PCI or coronary artery bypass grafting (CABG) was the highest among all analyzed groups. In 3-year observation the risk of death as well as myocardial infarction (MI) and major adverse cardiac events (MACE) in unstable angina after PCI was higher than in stable angina but considerably lower than in NSTEMI group. Multivariate analysis confirmed that prognosis in NSTEMI was substantially worse in comparison with UA (RR 1.365, 95% CI: 1.126–1.655, p=0.0015). On the contrary there were no difference in mortality risk between UA and SCAD patients (RR 1.189, 95% CI: 0.932–1.518, p=0.1620). Parallel results were observed in respect of MI and MACE. Independ predictors of death were: age, kidney disease, hypertension, diabetes, previous stroke or previous PCI. Multivariate logistic regression analyse Clinical presentation Death Myocardial infarction MACE RR 95% CI p-value RR 95% CI p-value RR 95% CI p-value NSTEMI/UA 1.365 1.126–1.655 0.0015 1.822 1.076–3.055 0.0260 1.514 1.267–1.807 <0.0001 NSTEMI/SCAD 1.624 1.251–2.109 0.0003 1.882 0.982–3.789 0.0568 1.604 1.275–2.094 <0.0001 UA/SCAD 1.189 0.932–1.518 0.1620 1.033 0.557–2.034 0.9219 1.060 0.855–1.323 0.6023 MACE, major adverse cardiac events; NSTEMI, non-ST-segment elevation myocardial infarction; UA, unstable angina; SCAD, stable angina. Conclusion Unstable angina accounted for 38% of all cases and was the most common diagnosis in patients that underwent PCI in that time. 3-year prognosis in UA was considerable better in comparison with NSTEMI. On contrary there was no difference in outcomes (death, MI, MACE) between UA and SCAD patients.

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Effect of remote ischemic post conditioning on kidney function in STEMI patients undergoing primary percutaneous coronary intervention

European Heart Journal Acute Cardiovascular Care ◽

10.1093/ehjacc/zuab020.110 ◽

2021 ◽

Vol 10 (Supplement_1) ◽

Author(s):

D Arara ◽

M Fadil ◽

Y Karani ◽

RD Nindrea

Keyword(s):

Myocardial Infarction ◽

Percutaneous Coronary Intervention ◽

Kidney Function ◽

Primary Percutaneous Coronary Intervention ◽

Coronary Intervention ◽

Control Group ◽

P Value ◽

Baseline Characteristic ◽

Simple Method ◽

Percutaneous Coronary

Abstract Funding Acknowledgements Type of funding sources: None. Background Primary percutaneous coronary intervention (PPCI) is a treatment of choice in ST elevation myocardial infarction patients (STEMI). However, this approach could affect the kidney function due to iodinated contrast exposure to the patient. Remote ischemic post conditioning (RIPostC) is a non-invasive and simple method that not only has cardioprotective but also renoprotective effect for kidney function. Purpose The aim of this study was to investigate the effect of RIPostC to kidney function in STEMI patients undergoing PPCI. Methods This study uses pre and post-test only with control group design with experimental research designs. Data was taken at an Indonesian Heart Center from June 2019 until March 2020, there were 66 patients with ST-segment elevation myocardial infarction (STEMI) being performed RIPostC procedure with intermittent ischaemia and reperfusion applied to the arm through five cycles of 5-min inflation and 5-min deflation of an automated cuff device after crossing wire. Creatinine and eGFR were measured pre and 48 hours post PPCI. Kidney function were determined by eGFR post PPCI, ΔeGFR (pre and 48 hours post PPCI), creatinine post PPCI and Δcreatinine (pre and 48 hours post PPCI). Bivariate analysis was performed to determine the effect RIPostC to kidney function using the Chi-square test. Result A total of 66 patients who underwent the PPCI procedure were divided into two groups RIPostC (n = 33) and without RIPostC (n = 33). The baseline characteristic in both of group was similar. We found that there were no differences of eGFR (70,46 ± 23,06 vs 65,88 ± 23,36, p = 0,424), ΔeGFR (0 [-34,68 - 37,32] vs 0 [-121,53 - 29,70], p value= 0,406), creatinine (1,00 [0,70 - 4,60] vs 1,20 [0,60-4,10], p value= 0,633) and Δcreatinine (0 [-1,20-1,10] vs 0 [-0,50-0,90], p value= 0,390) RIPostC group had a lower CI-AKI incident if we compare with the non RIPostC (15,2% vs 42,4%, p < 0,05). Conclusion Remote ischaemic conditioning does not significantly improve kidney function (eGFR, ΔeGFR, creatinine and Δcreatinine) in patients with STEMI undergoing PPCI The differences of kidney functionVariableRIPostCControlp valueeGFR post PPCI (ml/min/1,73 m2), mean70,46 ± 23,0665,88 ± 23,360,424aΔeGFR(ml/min/1,73 m2), median0 [-34,68 - 37,32]0 [-121,53 - 29,70]0,406bCreatinine post PPCI (mg/dL), median1,00 [0,70 - 4,60]1,20 [0,60-4,10]0,633bΔcreatinine (mg/dL), median0 [-1,20-1,10]0 [-0,50-0,90]0,390ba = Independent sample T testb = mann whitney testAbstract Figure. ΔeGFR and Δcreatinine pre and post PPCI

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Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection

BMC Immunology ◽

10.1186/s12865-021-00400-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Birhan Alemnew ◽

Soren T. Hoff ◽

Tamrat Abebe ◽

Markos Abebe ◽

Abraham Aseffa ◽

...

Keyword(s):

Mrna Expression ◽

Expression Patterns ◽

Fold Change ◽

Mrna Levels ◽

Healthy Children ◽

Toll Like Receptors ◽

Relative Expression ◽

Latently Infected ◽

Latent Tb ◽

Latent Tb Infection

Abstract Background Understanding immune mechanisms, particularly the role of innate immune markers during latent TB infection remains elusive. The main objective of this study was to evaluate mRNA gene expression patterns of toll-like receptors (TLRs) as correlates of immunity during latent TB infection and further infer their roles as potential diagnostic biomarkers. Methods Messenger RNA (mRNA) levels were analysed in a total of 64 samples collected from apparently healthy children and adolescents latently infected with tuberculosis (n = 32) or non-infected (n = 32). Relative expression in peripheral blood of selected genes encoding TLRs (TLR-1, TLR-2, TLR-4, TLR-6 and TLR-9) was determined with a quantitative real-time polymerase chain reaction (qRT-PCR) using specific primers and florescent labelled probes and a comparative threshold cycle method to define fold change. Data were analysed using Graph-Pad Prism 7.01 for Windows and a p-value less than 0.05 was considered statistically significant. Results An increased mean fold change in the relative expression of TLR-2 and TLR-6 mRNA was observed in LTBI groups relative to non-LTBI groups (p < 0.05), whereas a slight fold decrease was observed for TLR-1 gene. Conclusions An increased mRNA expression of TLR-2 and TLR-6 was observed in latently infected individuals relative to those non-infected, possibly indicating the roles these biomarkers play in sustenance of the steady state interaction between the dormant TB bacilli and host immunity.

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Clinical significance of Q waves in ischemic cardiomyopathy

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.340 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

E Rodenas Alesina ◽

P Jordan ◽

L Herrador ◽

C Espinet-Coll ◽

N Pizzi ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Primary Endpoint ◽

Ischemic Cardiomyopathy ◽

Cox Regression ◽

Cox Model ◽

Cardiovascular Death ◽

P Value ◽

Heart Failure Hospitalization ◽

Total Cohort

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): CIBER-CV AIMS The scintigraphic translation of Q waves in patients with ischemic cardiomyopathy and LVEF < 40% has not yet been assessed. The aim of this study was to explore the relationship between Q waves and necrotic tissue and to analyze their impact in prognosis. METHODS AND RESULTS A retrospective study enrolling 487 consecutive patients (67,0 [57,4 – 75,4] years), with ischemic cardiomyopathy, LVEF <40% and narrow QRS who underwent stress-rest SPECT was conducted. Patients with Q waves (320 patients [65,7%]) had less comorbidity and ischemia, but more necrosis. Q waves correlated poorly with lack of viability (AUC = 0,63) and were independently associated with the subendocardial extent of the necrosis. After a follow-up of 5,07 years, the primary outcome (cardiovascular death, heart failure hospitalization or myocardial infarction) occurred in 192 (39,4%) patients, without differences between groups in multivariate analysis. After accounting for non-cardiovascular death as a competitive risk, the interaction between >10% of ischemia and revascularization remained in Cox model both in the total cohort (aHR= 0,46 [0,24 – 0,86]), and in patients with Q waves (aHR = 0,27 [0,11–0,69]). CONCLUSION Patients with ischemic cardiomyopathy with Q waves have larger subendocardial scarring and more transmural necrosis, although correlation between Q waves and transmural scarring is poor. Revascularization if >10% ischemia is present is associated with a better prognosis. Ischemia burden should be assessed and accordingly treated in these patients, and no differences in management should be made in the presence of Q waves. Table 1. Cox proportional hazards model Total cohort (N = 471) Patients with Q waves (N = 315) aHR p-value 95% CI aHR p-value 95% CI Age (per year) 1,02 0,007 1,01 - 1,04 n.s. Diabetes mellitus 1,35 0,047 1,00 - 1,81 1,54 0,016 1,09 - 2,20 eGFR < 60 ml/min 1,59 0,005 1,15 - 2,21 1,96 <0,001 1,36 - 2,82 Previous HF hospitalization 1,71 0,002 1,23 - 2,38 1,76 0,007 1,17 - 2,64 Previous PCI 1,32 0,069 0,98 - 1,78 n.s. Previous CABG n.s. 1,77 0,009 1,15 - 2,72 Angina or dyspnea 1,68 0,001 1,24 - 2,28 1,71 0,004 1,19 - 2,46 Indexed TDV (per quartile) 1,16 0,047 1,02 - 1,33 n.s. Revascularization*ischemia > 10% 0,46 0,015 0,24 - 0,86 0,27 0,006 0,11 - 0,69 Cox regression for the primary endpoint (cardiovascular death, heart failure hospitalization or myocardial infarction), accounting for non-cardiovascular death as a competitive risk. Abstract Figure. Survival for the primary endpoint

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Sex Differences in Circadian Clock Genes and Myocardial Infarction Susceptibility

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8050053 ◽

2021 ◽

Vol 8 (5) ◽

pp. 53

Author(s):

Ivana Škrlec ◽

Jasminka Talapko ◽

Martina Juzbašić ◽

Robert Steiner

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Disease ◽

Circadian Rhythm ◽

Single Nucleotide Polymorphisms ◽

Clock Genes ◽

P Value ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Biological Sex ◽

Significant Difference

The growing body of evidence shows a significant difference in the circadian rhythm of cardiovascular disease based on biological sex. The incidence of cardiovascular disease varies between women and men. Additionally, biological sex is vital for the timely application of therapy—chronotherapy, which benefits both sexes. This study aimed to examine the potential difference of single nucleotide polymorphisms (SNPs) of the circadian rhythm genes ARNTL, CLOCK, CRY2 and PER2 in women and men with myocardial infarction. A cross-sectional study was conducted, including 200 patients with myocardial infarction. Altogether, ten single nucleotide polymorphisms in the ARNTL, CLOCK, CRY2 and PER2 genes were analyzed. The Chi-square test yielded statistically significant differences in CLOCK gene rs11932595 polymorphism in a recessive genotype model between women and men with a p-value of 0.03 and an odds ratio 2.66, and a corresponding 95% confidence interval of 1.07 to 6.66. Other analyzed polymorphisms of the circadian rhythm genes ARNTL, CRY2, and PER2 did not significantly differ between the sexes. According to the study’s current results, the CLOCK gene’s genetic variability might affect myocardial infarction concerning biological sex.

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Longitudinal change in left ventricular 4D flow kinetic energy after myocardial infarction

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.282 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

H Ben-Arzi ◽

A Das ◽

C Kelly ◽

RJ Van Der Geest ◽

A Chowdhary ◽

...

Keyword(s):

Myocardial Infarction ◽

Kinetic Energy ◽

Left Ventricular ◽

Three Dimensions ◽

Longitudinal Change ◽

P Value ◽

4D Flow ◽

Longitudinal Changes ◽

Funding Sources ◽

End Diastolic Volume

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation HRUK Background. Four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR) imaging provides quantification of intra-cavity left ventricular (LV) flow kinetic energy (KE) parameters in three dimensions. Myocardial infarction (MI) is known to cause acute alterations in intra-cardiac blood flow but assessments of longitudinal changes are lacking. Purpose. Assess longitudinal changes in LV flow post ST-elevation myocardial infarction (STEMI). Method. Twenty acutely reperfused STEMI patients (13 men, 7 women, mean age 54 ± 9 years) underwent 3T CMR acutely (within 5-7 days) and 3 months post-MI. CMR protocol included functional imaging, late gadolinium enhancement and 4D flow. Using Q-MASS, LV KE parameters were derived and indexed to LV end-diastolic volume (LVKEiEDV). Based on acute ejection fraction (EF), patients were grouped as follows: preserved (pEF) EF >50%, reduced (rEF) EF <50% including mild (rEF= 40-49%), moderate to severe (EF <40%) impairment. Results. Out of 20 patients, 13 had rEF acutely (7 mild rEF, 6 moderate to severe rEF). Acute LVKEiEDV parameters varied significantly between pEF and rEF (Table). At 3 months, pEF and mild rEF patients showed a significant (P < 0.05) reduction in average, systolic and peak-A wave LVKEiEDV. Mild rEF patients also had significant (P < 0.05) reduction in minimal and peak-E wave LVKEiEDV. However in patients with moderate to severe rEF in the acute scan, there were no significant change by 3 months (Figure). Conclusion. Following MI, 4D flow LVKE derived biomarkers significantly decreased over time in pEF and mild rEF groups but not in moderate to severe rEF group. 4D flow assessment might provide incremental prognostic value beyond EF assessment alone. Table pEF (n = 7) rEF (n = 13) V1 V2 P-value V1 V2 P-value EF(%) 56 ± 5 55 ± 4 0.40 41 ± 7 47 ± 9 0.01 Infarct Size(%) 31 ± 20 15 ± 9 0.04 18 ± 13† 16 ± 11 0.41 LV KEiEDV parameters Average(µJ/ml) 9 ± 2 7 ± 2 0.02 10 ± 3† 8 ± 3 0.01 Minimal(µJ/ml) 1 ± 0.6 1 ± 0.5 0.46 1.3 ± 0.5 1 ± 0.6 0.03 Systolic(µJ/ml) 10 ± 4 7 ± 2 <0.01 12 ± 4† 7 ± 3 <0.01 Diastolic(µJ/ml) 8 ± 3 7 ± 2 0.13 9 ± 3 8 ± 3 0.09 Peak-E wave(µJ/ml) 22 ± 9 23 ± 8 0.44 20 ± 7 18 ± 10 0.23 Peak-A wave(µJ/ml) 18 ± 10 11 ± 4 0.04 17 ± 9 14 ± 7 0.02 †P < 0.05 V1 comparison between pEF and rEF Abstract Figure

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Knowledge, attitude, and perception of oral and maxillofacial surgery specialty amongst healthcare professionals, and the General Public from a Gulf Cooperation Council (GCC) Country

BMC Surgery ◽

10.1186/s12893-021-01064-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mohammad Kamal ◽

Mohammad Abdulwahab ◽

Ahmed Al-Zaid

Keyword(s):

Cosmetic Surgery ◽

General Public ◽

Healthcare Professionals ◽

Maxillofacial Surgery ◽

P Value ◽

Oral And Maxillofacial Surgery ◽

Medical Doctors ◽

Surgical Specialty ◽

Cross Sectional ◽

Clinical Scenarios

Abstract Background Oral and maxillofacial surgery specialty has grown rapidly in Kuwait in recent years. However, the general public and healthcare professionals remain unaware of its expanding scope of practice. The aim of the study is to assess public and professional (dental and medical) perception of the oral and maxillofacial surgical specialty in Kuwait. Methods This is a cross-sectional study evaluating responses of dental professionals, medical professionals, and general public in Kuwait toward the oral and maxillofacial surgical specialty using a previously validated survey instrument with 100 participants in each group. Participants were asked to choose the most appropriate specialist to treat certain procedures across 4 disciplines: reconstruction, trauma, pathology, and cosmetic. Statistical comparison was conducted between dentists and medical doctors using Fisher’s exact test with a p-value of < 0.05. Results Disparities were noted each group’s responses. Oral and maxillofacial surgery was preferred overall for most clinical scenarios in trauma (p < 0.001), pathology (p < 0.001), and reconstructive surgery (p < 0.001). Plastic surgery was preferred for cosmetic surgeries (p < 0.001). Conclusions This study indicates the need to increase awareness especially towards cosmetic surgery procedures, and conduct health campaigns regarding oral and maxillofacial surgery among healthcare professionals, especially medical doctors, and the general public.

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Abstract 12117: The Cardioprotection of Trimetazidine Against Ischemic Injury is Mediated by AMPK and ERK Signaling Pathway

Circulation ◽

10.1161/circ.130.suppl_2.12117 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Zhenling Liu ◽

Yina Ma ◽

Michelle Kuznicki ◽

Xingchi Chen ◽

Wanqing Sun ◽

...

Keyword(s):

Myocardial Infarction ◽

Fatty Acid ◽

Fatty Acid Oxidation ◽

Glucose Oxidation ◽

Ex Vivo ◽

Ischemic Injury ◽

Erk Signaling ◽

Acid Oxidation ◽

Ampk Signaling ◽

Heart Perfusion

Introduction: Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. Hypothesis: AMP-activated protein kinase (AMPK) is an energy sensor that control ATP supply from substrate metabolism and protect heart from energy stress. TMZ changes the cardiac AMP/ATP ratio via modulating fatty acid oxidation, thereby it may trigger AMPK signaling cascade that contribute to protection heart from ischemia/reperfusion (I/R) injury. Methods: The mouse in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) were used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results: TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p<0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p<0.05). Intriguingly, the administration of ERK inhibitor, PD 98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Conclusions: Both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration.

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Abstract 17356: Gender Differences in Clinical Presentation and Outcomes of Patients With Acute Myocardial Infarction and Spontaneous Coronary Artery Dissection: A Nationwide Inpatient Sample Matched Analysis

Circulation ◽

10.1161/circ.138.suppl_1.17356 ◽

2018 ◽

Vol 138 (Suppl_1) ◽

Author(s):

Setri Fugar ◽

Juliet A Yirerong ◽

Alfred Solomon ◽

Ahmed A Kolkailah ◽

Tauseef Akthar ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Gender Differences ◽

Clinical Presentation ◽

Artery Dissection ◽

P Value ◽

Spontaneous Coronary Artery Dissection ◽

Coronary Artery Dissection ◽

Men And Women ◽

Significant Difference

Introduction: Spontaneous Coronary Artery Dissection (SCAD) is reported to occur predominantly in young women. Gender differences in the clinical presentation and outcomes of patients with SCAD have not been studied on a population level. We sought to compare the in-hospital outcomes of men and women presenting with acute myocardial infarction (AMI) and SCAD. Methods: We identified patients from the National Inpatient Sample (NIS) between 2005 and 2015 who presented with primary diagnoses of AMI and SCAD. We identified SCAD with ICD-9 code 414.12. A 1:1 propensity-matched cohort was created to examine the outcomes between men and women. Primary endpoint was in-hospital mortality. Secondary endpoints included in-hospital cardiac and non-cardiac complications. Results: Of the 6617 (32017 weighted national estimates) patients with SCAD over the study period, majority were males 3667 (55.4%). Males were younger than females (60.32 yr vs. 61.59 yr) and presented more often with ST-elevation myocardial infarction (STEMI) (53.0% vs. 45.9% P=<0.001). Propensity matching yielded 2366 males and 2366 females. In the matched group, there was no significant difference in in-hospital mortality between males and females (OR 1.20 95% CI -0.93-1.54). With regards to in-hospital complications, ventricular tachycardia (V-Tach) was significantly less frequent in females as compared to males (8.0% vs. 10.1% OR 0.76 p-value 0.003). There was no significant difference between females and males in the frequency of other complications, including intracranial hemorrhage (0.2% vs 0.2% OR 1.45 p-value 0.50), GI bleed (1.8% vs 1.3% OR 1.35 p-value 0.13), cardiogenic shock (9.8% vs 9.7% OR 1.01 p-value 0.86), acute heart failure (3% vs 2.6% OR 1.18 p-value 0.26), ventricular fibrillation(vfib) (5.6% vs 6.0% OR 0.928 p-value 0.48) or stroke ( 1.5% vs 1.0% OR 1.535 p-value 0.06) Conclusion: In our large population-based analysis, compared to females, males were more likely to present with STEMI as compared to females. With the except of V-Tach, which was higher in males, there were no significant gender differences in hospital outcomes namely inpatient mortality, cardiogenic, Vfib or acute heart failure.

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