Post MI Research Articles

Cardioprotection of Panax Notoginseng saponins against acute myocardial infarction and heart failure through inducing autophagy

Morbidity and mortality from acute myocardial infarction (AMI) remains substantial although interventional coronary reperfusion strategies are widely use and successful. MI remains the most common cause of heart failure (HF) worldwide. Here we demonstrated that Panax Notoginseng saponins (PNS), the extract of Panax notoginseng, exerts cardioprotective effect in AMI and the underlying mechanism refers to inducing cardiomyocyte autophagy, antiplatelet aggregation, enhancing endothelial migration and angiogenesis. PNS was initially tested to rescue the myocardial infarct size and cardiac function in left anterior descending (LAD) ligation-operated mice to mimic AMI. RNA-seq to profile transcriptome changes in the heart by treatment with PNS were then conducted. PNS and its main constituents Rg1 and Rd directly inhibited platelet aggregation of healthy subjects with VerifyNow Aspirin and P2Y12 assays but less affecting on coagulation compared with dual-antiplatelet (DAPT). In addition, wound healing scratch assay and heart staining demonstrated that PNS and its main constituents Rg1 and R1 significant enhanced the migration of endothelial cells and angiogenesis in response to MI injury. Interestingly, PNS rather than its constituents enhanced glucose deprivation (GD)-induced autophagy through phosphorylation of AMPK Thr172 and CaMKII Thr287 in cardiomyocytes. These findings provide new insights for drug development from natural products like PNS against ischemia heart diseases and HF post MI.

IN-HOSPITAL EARLY COMPLICATIONS IN DIABETICS VS NON DIABETICS WITH ACUTE ST ELEVATION MYOCARDIAL INFARCTION AGE GROUP 30-70 YEARS

Objective: To determine in hospital early complications in diabetics’ vs non diabetics with acute ST elevation myocardial infarction.
 Study Design: Comparative cross-sectional study.
 Place and Duration of Study: The study was conducted in emergency departments and adult cardiology wards of Armed Forces Institute of Cardiology/National Institute of Heart Diseases, from Aug to Nov 2019.
 Methodology: A comparative cross sectional study was conducted on 380 patients (190 patients with diabetes and 190 patients without diabetes) who presented with acute ST-Elevation MI in age group 30 to 70 years to emergency department of Armed Forces Institute of Cardiology/National Institute of Heart Disease during specified period. Patients with rescue PCI and new onset of LBBB were also included. Patients with age group lesser than 30 years or greater than 70 years with STEMI were excluded. Sampled with consecutive non probability technique in patients was assessed with ECG, cardiac enzymes, transthoracic echocardiography, renal Doppler and RFTs. All patients were admitted in wards and were followed up during hospital stay. Patients were evaluated and their record of Primary PCI and thrombolysis was also noted. Data was entered and analyzed with SPSS-23.
 Results: A total of 380 patients with STEMI were included in this study consisting of 292 (76.8%) male and 88 (23.1%) female from 30 to 70 years. The patients were divided in two groups i.e. diabetic and non-diabetic, 190 patients were included in each group. It was found that frequency of ST-Elevation MI was higher in diabetic group as compared to non-diabetic group. All the patients were analyzed for complications occurred after STElevation MI. LV failure, Brady arrhythmias, atrial fibrillation, post MI angina and cardiogenic shock were the main complications noted. It was found that all these complications are more in diabetic group post MI angina which occurred most frequently in non-diabetic group.
 Conclusion: In our study we observed that left ventricular failure and arrhythmias were the major complications. Mortality was higher in diabetic patients than non-diabetic patients. In both groups PPCI and SK reduced mortality. Post MI angina were found more frequent in non-diabetic group.

Is Physical Therapy the Early Solution for Post-Acute Myocardial Infarction Patients? A Meta-Analysis

Abstract Background: Physical rehabilitation is essential to improve the quality of life of patients with acute myocardial infarction (AMI). Study aim: The study intended to demonstrate the benefits of early rehabilitation in patients with AMI. Material and method: We performed a meta-analysis to document the benefits of physical treatment in patients who suffered an AMI. Studies were searched in the following databases: PubMed, PlosOne, Mendeley, and clinicaltrials.gov. The terms used in our research were “rehabilitation”, “physical exercise”, “physical training” “quality of life”, “early”, and “post MI”. The inclusion criteria consisted in the assessment of the following parameters: heart rate, maximal/submaximal capacity, and characteristics of the left ventricle – end-diastolic volume, ejection fraction, and left ventricle hypertrophy included in the study design. Results: The database search identified 710 studies, of which only 10 passed the inclusion criteria. Out of 1,515 patients who underwent early physical therapy, 960 reported improvement in the quality of their life (p <0.001). A number of 2,703 patients out of a total of 3,595 underwent a complete physical treatment and medication program. From the ten studies included in the meta-analysis, six had a positive feedback to the multimodal treatment within 1 month post-AMI. Patients who performed physical exercises within a month after the cardiac arrest (1,103 post-AMI patients from a total of 1,278) demonstrated a high heterogeneity represented by the coefficient I2 = 84% but with a significant statistical value of p <0.00001. Conclusion: Early physical therapy initiation significantly improves the quality of life of patients with AMI.

A study of etiology, clinical characteristics, electrocardiographic and echocardiographic findings in patients with cardiac tamponade in a tertiary care hospital in Western Odisha

Background: Cardiac tamponade is a life-threatening condition characterized by elevated intracardiac pressure, limitation of diastolic filling, and reduction of cardiac output and mostly requires urgent therapeutic intervention. Pericardial disease in on the rise attributed to improved survival of malignancy, growing no of cardiac interventions, chronic kidney diseases with dialysis, advent of modern chemo-radiotherapy. Still, there are paucity of data on etiology, clinical characteristics, electrocardiogram (ECG) and echocardiographic features in patients with cardiac tamponade from Odisha. Aim of this study was to emphasize the etiology, clinical characteristics, electrocardiographic and echocardiographic features in patients with cardiac tamponade.Methods: A prospective observational study of 1-year duration was undertaken for patients with cardiac tamponade admitted at VIMSAR, a cardiology unit. Data on etiology, clinical characteristics, Echocardiography, ECG findings were documented. Echo guided pericardiocentesis followed culture, cytological and biochemical analysis done.Results: Most common symptom was dyspnoea (88%), clinical signs were tachypnoea (96%), raised jugular venous pulse (64%), tachycardia (84%), pulsus paradoxus (60%). Classical beck’s triad was seen in 42% cases. X-ray showed cardiomegaly (94%) & pleural effusion (64%). Common ECG findings were sinus tachycardia (84%), low voltage QRS (68%) and electrical alternans (44%). Echocardiography showed 80% and 68% of patients had right atrium collapse and right ventricle collapse respectively. Both inferior vena cava plethora and transmitral flow variation were seen in 88% of cases. 96% had normal left ventricle function. 80% had large effusion. Pericardiocentesis yield was mostly in between 500-1000ml (mean 908 ml) with 72% with haemorrhagic aspirate. All malignancy cases and 76% tubercular cases had haemorrhagic effusion. Most common etiology was tubercular (50%), followed by malignancy (28%). 6% remained idiopathic. chronic kidney disease, systemic lupus erythematosus, post MI intervention, hypothyroid were some of the other causes.Conclusions: Initial assessment with investigation and careful follow-up can yield a causal diagnosis in most cases. Early diagnosis and intervention by pericardiocentesis can be lifesaving.

Abstract 17179: Stress-Mediated Platelet Activation Contributes to Thrombosis: Findings From the American Heart Association Go Red for Women Strategically Focused Research Network

Background: Psychological stress is a risk factor for cardiovascular disease (CVD). Despite advancements in CV-prevention, CVD remains the global leading cause of disease burden, suggesting that additional factors contribute to sustained CV risk. The mechanisms by which stress contributes to increased CVD are largely unknown. However, in preclinical models increased sympathetic nervous system activity promotes systemic inflammation (e.g. monocyte activation, cytokine production), and may underlie increased CVD risk. We investigated perceived stress in women with MI and its association with platelet activity, and validated our findings in a murine model. Methods: Monocyte-platelet aggregates (MPA) and psychological stress, using the validated Perceived Stress Scale (PSS4), were measured in women post MI (n=96; median age 62.2 years) and in control women (n=31; 66.7 years). A mouse model of chronic variable stress was utilized to explore the impact of stress on platelet activity and risk of thrombosis-mediated death. Results: Perceived stress was higher in MI patients than matched women (p=0.009). Platelet activity, assessed by MPA, was significantly elevated in MI vs. controls (p=0.0025). MPA significantly correlated with PSS4 scores (R=0.412, p =0.009). In a female mouse model of chronic variable stress, circulating MPA was increased in stressed mice compared to controls (p<0.05), and platelet activation markers P-selectin and JON/A were increased on platelets from stressed mice relative to stress free mice (p<0.05). Using a platelet mediated thrombosis model, time to thrombosis and survival was reduced in stressed mice. Conclusion: Platelet activity was increased at the time of MI in women, and positively associated with stress. In a mouse model, we find that stress is a significant contributor to increased platelet reactivity, and promotes thrombosis-mediated death. Cross-talk between platelets and monocytes is a critical mechanism linking thrombosis and inflammation, thus stress-induced MPAs may represent an unexplored pathway linked to stress-mediated CVD-risk. Future studies will examine whether reducing stress reduces platelet hyperactivity and MI risk.

Abstract 15792: Etiology, Treatment and Outcomes in Patients With Left Ventricular Thrombus - Experiences From an African Center

Introduction: Left ventricular thrombus (LVT) may lead to thromboembolism and has been associated with increased morbidity and mortality. Little is known about the incidence, etiology and outcomes in patients with LVT in Africa. Objectives: To determine the etiology, treatment practices, rate of resolution and outcomes in patients with LVT in the region. Methods: A review of all echocardiograms performed in 2017 and 2018 at the Aga Khan University Hospital, Nairobi was carried out and patients with LVT identified. Physician review of charts was performed to document clinical characteristics and outcomes. Results: During the study period 100 patients with LVT were identified (1.3% of adult echoes). The mean LVEF was 28.5% (±11.0%) and 88% of the patients had an LVEF of less than 40%. Underlying etiology of LV dysfunction was post MI in 28%, chronic ischemic cardiomyopathy in 42% and non ischemic cardiomyopathy in 30%. In 15% of the patients a stroke or TIA predated the diagnosis of LVT. Long term anticoagulation was given to 92 patients. Among these, 37% received warfarin while 63% were treated with a DOAC (rivaroxaban (50%), dabigatran(7.6%) and apixaban(5.4%)). In 60% of the patients, anticoagulation was continued beyond a year. In patients with reassessment imaging (64%, median time 177 days), complete thrombus resolution was noted in 59.4%. One year follow-up data was available for 85 patients: 13 (15.3%) patients had died, 4 (4.7%) had suffered a stroke, and 8(9.4%) had a bleeding episode. Rates of thrombus resolution, stroke and bleeding were not significantly different among patients treated with warfarin and DOAC (Figure 1). Conclusions: We noted a high incidence of LVT compared to contemporary Western series. The majority of our patients were treated with DOACs. There were no significant differences in outcomes between patients treated with a DOAC and those receiving warfarin. Prospective evaluation on the efficacy and safety of DOACs for this indication is needed.

Prognosis in patients with prior myocardial infarction and PEGASUS-TIMI 54 criteria in the CLARIFY registry

Abstract Background/Introduction The PEGASUS-TIMI 54 trial showed that prolonged treatment with ticagrelor reduces the cumulative occurrence of ischemic adverse events. CLARIFY is the biggest real life registry on chronic coronary syndrome. Purpose - To evaluate the percentage of patients eligible for long-term ticagrelor therapy in the CLARIFY registry. – To compare the outcome of this subgroup of patients with those with PEGASUS exclusion criteria or without PEGASUS inclusion criteria. Methods Within the CLARIFY population, we selected post MI patients and we excluded those with missing info (post MI evaluable population). Then, we divided patients into 3 groups: excluded (meeting PEGASUS exclusion criteria, namely use of P2Y12 receptor antagonists or chronic oral anticoagulant, any stroke, coronary-artery bypass grafting in the past 5 years); eligible (meeting PEGASUS high-risk inclusion criteria, namely age≥65 years; diabetes; multivessel disease; creatinine clearance <60 ml/min) and ineligible (not meeting PEGASUS high-risk inclusion criteria). We therefore compared the ischemic (CV death, MI and stroke) and bleeding (major bleeding) outcome of the 3 groups adjusting for age, sex, smoking and geographical region. Results Among the 11811 post-MI evaluable patients, 4706 (39.8%) were included in the eligible group, 5715 (48.4%) in the excluded group, and 1390 in the ineligible group (11.8%). Both the ischemic and bleeding endpoints were significantly different among the 3 groups with the excluded patients with the worst and ineligible patients with the best outcome (see table). The same trend was shown for CV death, while the occurrence of MI was not significantly different among the 3 groups. In the eligible group, the ratio between ischemic and bleeding events was 6:1, whereas between CV death and major bleeding was 3.5:1. Conclusions Around 40% of CLARIFY post-MI patients could benefit from prolonged ticagrelor therapy. In this group of patients, ischemic risk seems to be higher than the bleeding one. Ischemic & bleeding risk in the 3 groups Funding Acknowledgement Type of funding source: Private company. Main funding source(s): CLARIFY registry was funded by Servier

MicroRNA-146a regulates angiogenesis and functional regeneration after myocardial infarction

Abstract Background The growth or regeneration of new blood vessels is critical for physiological angiogenesis and for tissue repair in response to injury, such as myocardial infarction. However, the mechanisms underlying the angiogenic processes and, specifically, the regulation of neo-vascularization by microRNAs are not well understood. Purpose To study the potential beneficial role of miRNA-146a in vessel regeneration after myocardial infarction. Methods Mice were subjected to myocardial infarction or hind limb ischemia and vascular development was followed in zebra fish. microRNA-146a was blocked or overexpressed in endothelial cells in vitro or in mice or zebra fish in vivo. Furthermore, Blood samples from patients with ST-elevation myocardial infarction (STEMI) were studied for miR-146a expression. Results MicroRNA-146a was upregulated in the ischemic hind limb following ligation of the femoral artery and in the ischemic myocardium in male C57BL/6 mice following ligation of the left anterior descending (LAD) artery, as well as in patients with STEMI. In vitro, overexpression of microRNA-146a significantly attenuated endothelial cell proliferation and migration, abolished endothelial capillary network formation, and inhibited cell sprouting from endothelial spheroids. In contrast, microRNA-146a silencing had opposite effects. Mechanistically, Nox4, Notch1, and nRas were identified by in silico prediction and microarray mRNA expression analysis, and validated as direct targets and effector molecules of microRNA-146a in endothelial cells according to mRNA and protein expression profiles, as well as luciferase gene reporter assays and respective rescue experiments. In zebrafish, overexpression of microRNA-146a inhibited the development of the trunk vasculature. Blocking the upregulation of endothelial microRNA-146a in mice,using specific inhibitors, resulted in significantly enhanced 1 angiogenesis and revascularization both in an ischemic hind limb model and in the infarcted myocardium. This was accompanied by a significantly reduced myocardial infarct size and preserved cardiac function post MI. Conclusions Our findings identify microRNA-146a as a critical regulator of angiogenesis and vascular regeneration. Inhibition of microRNA-146a may represent an attractive strategy for the angiogenic therapy of ischemic tissue diseases. Funding Acknowledgement Type of funding source: None

Post-load glucose spike is a determinant of post-MI prognosis in patients without known or newly diagnosed diabetes

Abstract Background Post-prandial plasma glucose spikes contribute to the progression of atherosclerosis. Glycaemic variability may predict post-ACS prognosis. A third to two-thirds of these patients had diabetes mellitus (DM). Post-ACS prognosis is worse in DM than in those without. This has not been tested in patients without DM. Purpose To test whether post-load spike in plasma glucose in patients without known or newly diagnosed DM adversely affects prognosis. Methods Retrospective cohort analysis of 847 MI survivors without known or newly diagnosed DM who were followed up for MACE (death and non-fatal MI). The median post-glucose spike (PGS, defined as the difference between the 2h-PG and FPG) was 2.4 mmol/l for the whole cohort and 1.5 mmol/l for the patients with normal glucose tolerance (NGT). Group 1: PGS ≤2.4 mmol/l and Group 2: PGS >2.4 mmom/l were compared using Mann-Whitney test for continuous variables and chi-squared test for categorical variables. Event free survival in the two groups was estimated from the Kaplan–Meier curves and compared using log-rank test. Cox proportional hazard regression identified predictors of MACE. Continuous net reclassification improvement (NRI>0) and integrated discrimination improvement (IDI) and c-statistics determined the added predictive value of glycaemic matrices Results MACE was higher in group 2 (OR 1.99, 95% CI 1.36 to 2.91, p=0.0004) compared to group 1. In patients with NGT, MACE was higher in patients with PGS ≥1.5 mmol/l vs those below (OR 2.37, 95% CI 1.31 to 4.26, p=0.0041). Event free survival was worse in pre-diabetes than in the NGT groups (HR 1.57, 95% CI 1.17 to 2.12, p=0.003). and in group 2 than 1 (HR 2.01, 95% CI 1.49 to 2.71, p<0.001). Amongst the patients with NGT, event free survival was worse in patients with PGS ≥1.5 mmol/l (HR 2.09, 95% CI 1.35 to 3.25, p<0.001). PGS independently predicted MACE in the whole cohort (HR 1.16, 95% CI 1.06 to 1.26, p=0.002) and NGT group (HR 2.06, 95% 1.51 to 2.79, p<0.000). Group 2 independently predicted MACE in the whole cohort (HR 1.75, 95% CI 1.26 to 2.42, p<0.001). In the NGT group, PGS >median, independently predicted of MACE (HR 2.67, 95% CI 1.54 to 4.61, p<0.001). The c-statistic a model containing GRS only increased on addition of PGS (δAUC 0.0134, p=0.046) but not on addition of FPG. Within the whole cohort, PGS improved the net reclassification by 28% when added to the model containing GRS only. NGT cohort had higher net improvement at 46.6%. Addition of PGS to the model containing GRS and FPG resulted in NRI>0 of 25.5% in the whole cohort and 56.3% in the NGT cohort. Similar changes were seen in the IDI. Conclusion(s) PGS predicts post MI prognosis in patients without known or newly diagnosed DM including in patients with NGT. This suggests that PGS is a more powerful indicator of post-MI prognosis than FPG Funding Acknowledgement Type of funding source: None

PREDICTING PERSISTENT LEFT VENTRICULAR DYSFUNCTION FOLLOWING MYOCARDIAL INFARCTION

The use of ICDs has led to a reduction in mortality in patients with persistent left ventricular dysfunction after a MI. However, studies have failed to demonstrate a decrease in mortality with early implantation post MI. The PREDICTS score (PREDiction of ICd Treatment Study) has recently been developed to predict LVEF recovery to >35% at 90-day post MI in patients with acute MI and severe left ventricular dysfunction. A higher score (ranging from 0 to 8) is associated with a higher likelihood of recovery. This tool could allow early identification of patients who are at high risk of sudden cardiac death and will likely need an ICD. We aim to validate this score in an external cohort.

Proposal for a standardized discharge letter after hospital stay for acute myocardial infarction.

In patients admitted for acute myocardial infarction, the communication and transition from specialists to primary care physicians is often delayed, and the information imparted to subsequent healthcare providers (HCPs) may be sub-optimal. A French group of cardiologists, lipidologists and diabetologists decided to establish a consensus to optimize the discharge letter after hospitalization for acute myocardial infarction. The aim is to improve both the timeframe and the quality of the content transmitted to subsequent HCPs, including information regarding baseline assessment, procedures during hospitalization, residual risk, discharge treatments, therapeutic targets and follow-up recommendations in compliance with European Society of Cardiology guidelines. A consensus was obtained regarding a template discharge letter, to be released within two days after patient's discharge, and containing the description of the patient's history, risk factors, acute management, risk assessment, discharge treatments and follow-up pathway. Specifically for post acute MI patients, tailored details are necessary regarding the antithrombotic regimen, lipid-lowering and anti-diabetic treatments, including therapeutic targets. Lastly, the follow-up pathway needs to be precisely mentioned in the discharge letter. Additional information such as technical descriptions, imaging, and quality indicators may be provided separately. A template for a standardized discharge letter based on 8 major headings could be useful for implementation in routine practice and help to improve the quality and timing of information transmission between HCPs after acute MI.

In-hospital Outcome of Percutaneous Coronary Intervention among Very Elderly Patients with Ischemic Heart Disease in a Dedicated Cardiac Hospital

Background: Cardiovascular disease, and ischemic heart disease (IHD), is a major cause of morbidity and mortality in the very elderly patients (>80 years) worldwide. These patients represent a rapidly growing cohort presenting for percutaneous coronary intervention (PCI), now constituting more than one in five patients treated with PCI in real-world practice. Furthermore, they often have greater ischemic burden than their younger counterparts, suggesting that they have greater scope of benefit from coronary revascularization therapy. The elderly usually has higher prevalence of co morbidities and more often experience complications during and after revascularization procedures. Our aim was to evaluate clinical outcomes of PCI in patients older than 80 years, compared to their younger counterparts.
 Materials and methods: From July 2017 to July 2018 we included 212 patients with IHD purposively in Cardiology department of National Institute of Cardiovascular Diseases undergone PCI who were divided into 2 groups according to age: e” 80 years (n = 74) and < 80 years (n = 138). Baseline clinical characteristics, indications for coronary intervention, in hospital outcomes were obtained. Study endpoint were Renal impairment, MI, LVF, emergency revascularization and death.
 Results: Very elderly patients were more frequently male (86%) and nonsmoker at present (41% vs. 63%, p=0.003), had higher prevalence of hypertension (60% vs. 50%, p<0.13), and more often presented with NSTEMI (54% vs. 23%, p<0.001). Elderly group had higher incidence of TVD and LM disease (36% vs. 26% and 9.5% vs. 2.9%, p=0.07) and more incidence of ostial (16.2% vs.5.1%,p=0.007) and calcified lesions (31.1% vs. 14.5%, p=0.004). Procedural success (TIMI III) were high in both groups, but still lower in the elderly as compared to younger group (95% vs. 97%, p=0.65). Very elderly patients had higher incidence of post PCI bleeding, CIN, MI, LVF and death (9.5% vs.6.1%, 8.2% vs.3.7%, 6.8% vs.5.8%, 9.5% vs. 5.1% and 5.4%vs.3.6%,p=0.07), whereas emergency revascularization were higher in younger group (5.4% vs. 6.5%, p=0.07).
 Conclusion: Very elderly patients aged ≥80 years face more vascular site complications during PCI, usually have more LM and TVD with more ostial and calcified lesions in comparison with younger group. Though procedural success is similar with younger group, they face more post PCI CIN, LVF and MI. Repeat revascularization was higher in younger group.
 Bangladesh Heart Journal 2020; 35(1) : 61-65

Epidemiological Variation of Acute Myocardial Infarction Relevant to In-Hospital Outcomes-Tertiary Center Experience-Saudi Arabia.

BackgroundEpidemiological related differences in patients presenting with ST-elevation myocardial infarction (STEMI) have not yet been fully characterized in the Middle East countries. The aim of this study was to assess gender, ethnic and racial variation in clinical profiles, presentation and treatment strategies with relation to the in-hospital outcomes.MethodThis is a retrospective, single center study reviewing the epidemiological details of STEMI patients who were admitted to our center during the period between October 2015 and August 2019.ResultOut of 3079 patients presented with STEMI, 498 (16%) were women, 2170 (70%) were from Middle Eastern Countries and only 1200 (39%) were non- Arabic speakers. Women were older in age compared to men (60.04 ± 11.2 vs 55.35 ± 11.8; P < 0.001). They showed significantly higher rates of cardiovascular risk factors (P < 0.001 for diabetes mellitus (DM), hypertension (HTN) and obesity) and lower prevalence of smoking and old history of previous revascularization (P < 0.001 and 0.007, respectively). Middle Eastern Countries- STEMI patients were elderly, showed higher prevalence of DM, HTN, smoking and obesity compared to South Asian patients (p = 0.001, 0.057, <0.001, <0.001 respectively). Arabic speaking - STEMI patients showed more prevalence of DM, smoking and obesity compared to non-Arabic speaking patients (p < 0.001). Regarding STEMI localization, post myocardial infarction complications and in-hospital length of stay, there were no detected significant gender, ethnic or racial variation. Women showed higher rates of all in-hospital mortality compared to men (5% vs 3%; p = 0.027) however, no ethnic/racial mortality difference was recorded among STEMI patients. Being elderly, presence of multivessel coronary artery disease and left ventricular systolic dysfunction (LVEF < 30%) are the three independent predictors of mortality among our patients (p = 0.013, 0.048 and <0.0001 respectively).ConclusionOur study demonstrates that there are gender, ethnic/racial-related differences in the demographics and clustered cardiovascular risk factors. However, there were no significant detected variation between both genders and different ethnic groups regarding post MI complications, management provided, and hospital outcomes except for increased the mortality rates among women. Old age, presence of multi-vessel disease and severe left ventricular systolic dysfunction have the greatest effect on in-hospital mortality among STEMI patients.

An Observational Study to Assess Outcome of NSTEMI Patients with Raised Serum Uric Acid Level in a Tertiary Care Hospital of Bangladesh

Background: Non-ST segment elevation myocardial infarction (NSTEMI) is the commonest form of ACS and a leading global cause of premature morbidity and mortality. Evidences link serum uric acid with short and long-term major adverse outcomes (MACE) in patients with NSTEMI. Objective: To see in-hospital outcome of NSTEMI patients with raised serum uric acid level. Methodology: This cross-sectional observational study was conducted in the Department of Cardiology, Sylhet MAG Osmani Medical College Hospital, Sylhet during the period from July, 2017 to June, 2019. Fifty NSTEMI patients with raised serum uric acid (&gt;7mg/dl in male; &gt;6mg/dl in female) level (Group A) and fifty NSTEMI patients with normal serum uric acid level (group B) admitted within 24 hours of symptom onset were consequently enrolled. In-hospital complications and mortality were recorded while continuing standard treatment for the event. Results: The mean age was 60.82 (SD 9.62) years in group A and 49.90 (SD 10.40) years in group B. The mean age of the patients of group A was significantly higher than patients of Group B (p&lt;0.001). Male preponderance was in both groups (84.0% versus 80.0%; p=0.603). Diabetes mellitus (52.0% versus 22.0%; p=0.002), hypertension (78.0% versus 52.0%; p=0.039) and dyslipidaemia (48.0% versus 12.0%; p&lt;0.001) were more frequent in group A than that of group B. But smoking status (70.0% versus 66.0%; p=0.668), family history of CAD (10.0% versus 26.0%; p=0.476) did not differ significantly. Killip class did not differ significantly between group A and group B (p=0.127). In-hospital mortality was 5 (10.0%) patients in group A and 2 (4.0%) patients in group B; did not reach the level of significance (p&gt;0.05) and complications such as post MI angina, cardiogenic shock, acute left ventricular failure, re-infarction, sinus tachycardia, sinus bradycardia, atrial flutter, atrial fibrillation, bundle branch block, ventricular tachycardia, ventricular fibrillation did not differ significantly between the two groups (p&gt;0.05). Conclusion: There is no significant difference between in-hospital outcome (mortality and complications) of NSTEMI patients with raised and normal serum uric acid level.

FREQUENCY OF IN HOSPITAL MORTALITY IN PATIENTS WITH HIGH NEUTROPHIL/LYMPHOCYTE RATIO PRESENTING WITH ST ELEVATION MYOCARDIAL INFARCTION

Objective: To determine the frequency of in-hospital mortality in patients with high NLR presenting with STEMI. Methodology: Consecutive patients with STEMI and high NLR presenting at Cardiology department, Lady Reading Hospital, Peshawar were evaluated for our study. Out of the 236 patients admitted from 1st September 2015 to 28th February 2016, 191 patients qualified for study inclusion. NLR was calculated by dividing the total number of neutrophils over the total number of lymphocytes obtained via a computerized heamogram. A high NLR was defined as value &gt;4.7. In hospital mortality and the effect of various class of patients with or without conventional risk factors was assessed. Results: The mean high NLR in study population was 6.38±1.28. In-hospital mortality due to cardiac cause was 12% (n=23) which included 8.37% (n=16) males. Statistically significant higher values of mean high NLR were found to be associated with in-hospital mortality and presence of conventional risk factors including hypertension, diabetes, and smoking with the exception of hypercholesterolemia. Among the patients who died, more had adverse events in form of higher Killip class and arrythmias. Conclusion: High NLR has fair prognostic value in patients presenting with acute STEMI. Raised values correlate well with the presence of conventional risk factors which increase the risk of post MI adverse events and appears additive to conventional risk factors and biomarkers. Key Words: ST elevation myocardial infarction (STEMI), Neutrophil to lymphocyte ratio (NLR), Total leucocyte count (TLC), Coronary artery disease (CAD), Acute coronary syndrome (ACS)

Hematopoietic Stem-Cell Senescence and Myocardial Repair: Coronary Artery Disease Genotype/Phenotype Analysis of Post-MI Myocardial Regeneration Response Induced by CABG/CD133+ Bone Marrow Hematopoietic Stem Cell Treatment in RCT PERFECT Phase 3

Objective: Clonal hematopoiesis with mutational gene dysregulation of hematopoietic stem cell (HSC) precursors for immune or endothelial progenitor cell response is suspected to affect coronary artery disease bypass surgery (CABG) induced ischemic myocardial repair. Design: Transcriptome and variant expression analysis was studied in the phase 3 PERFECT (post MI CABG and CD133 + BMSC or Placebo) trial in myocardial regeneration responders (R, n=14; ∆LVEF +16% day 180/0) and non-responders (NR, n=9; ∆LVEF -1∙1% day 180/0), then validated in independent patient cohort (n=14) as well as under mouse SH2B3/LNK antisense or knockout deficient conditions. Findings: 1. Left ventricular functional recovery was accompanied by an increase in myocardial perfusion (R vs NR, p<0∙05). R differed from NR in a total of 161 genes in differential expression (n=23, q<0,05) and 872 genes in coexpression analysis (n=23, q<0,05). Machine Learning clustering analysis revealed distinct R vs NR preoperative gene-expression signature in peripheral blood. RvsNR ML-top selected genes were correlated to SH2B3 (p<0∙05). Mutation signature analysis performed by RNASeq revealed increased specific variants in NR vs R. (NR: 224 genes with 268 exon regions; R: 48 genes with 56 exon regions). 2. RvsNR ML-selected gene expression and phenotype was correlated to SH2B3 deficient mouse models. Competitive bone-marrow transplanted mice SH2B3/LNK silenced HSC clones displayed significant overgrowth of myeloid and immune cells in bone marrow, peripheral blood and tissue at day 160 after BMT. SH2B3/LNK-/- mice demonstrated enhanced cardiac repair through augmenting the kinetics of BM-derived EPCs, increased capillary density in ischemic myocardium and reduced left ventricular fibrosis with preserved cardiac function. 3. Validation analysis in 14 additional patients revealed 85% R vs NR prediction accuracy. Interpretation: Myocardial repair is affected by HSC gene response. Somatic mutation in adaptor proteins may alter response by clonal overgrowth as shown for SH2B3/LNK. ML guided predictions can be utilized to identify and predict pathological HSC response. Trial Registration: ClinicalTrials.gov NCT00950274 Funding Statement: German Ministry of Research and Education (BMBF): FKZ0312138A, FKZ031L0106C, EU ESF/IV-WM-B34-0011/08, ESF/IV-WM-B34-0030/10, and Miltenyi Biotec GmbH, Bergisch-Gladbach, Germany. Japanese Ministry of Health : Health and Labour Sciences Research Grant (H14-trans-001, H17-trans-002) Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: Approval by the Ethical committee, Rostock University Medical Center 2009; No. HV-2009-0012.

RETRACTED: Amphiregulin promotes cardiac fibrosis post myocardial infarction by inducing the endothelial-mesenchymal transition via the EGFR pathway in endothelial cells

The endothelial-mesenchymal transition (EndMT) plays a key role in the development of cardiac fibrosis (CF) after acute myocardial infarction (AMI). The results of our previous study showed that amphiregulin (AR) expression was enhanced after MI. However, the role of AR on EndMT post MI remains unknown. This study aimed to elucidate the impact of AR on EndMT post MI and the associated molecular mechanisms. AR expression was markedly enhanced in infarct border area post MI, and endothelial cells were one of the primary cell sources of AR secretion. Stimulation with AR promoted endothelial cell proliferation, invasion, migration, collagen synthesis and EndMT. In addition, EGFR and downstream gene expression was significantly enhanced. In vivo, EndMT was significantly inhibited after lentivirus-AR-shRNA was delivered to the myocardium post MI. In addition, silencing AR ameliorated cardiac function by decreasing the extent of CF. Furthermore, the levels of EGFR pathway components in endothelial cells extracted from infarct border myocardium were all significantly decreased in lentivirus-AR-shRNA-treated MI mice. Our results demonstrate that AR induces CF post MI by enhancing EndMT in endothelial cells. Thus, targeting the regulation of AR may provide a potentially novel therapeutic option for CF after MI.

SPONTANEOUS RESOLUTION OF VENTRICULAR STANDSTILL AFTER MYOCARDIAL INFARCTION WITH NON-OBSTRUCTIVE CAD

Ventricular Standstill is associated with electrolyte imbalances, increased vagal tone, and can occur post MI due to ischemia and subsequent conduction defects. A 64-year-old male presented with severe chest pain and nausea. His EKG had ST-elevations in the inferolateral leads. His initial cardiac

Serum IGF-1 düzeyleri akut miyokard infarktüsü sonrası gerçekten azalır mı ve sol ventrikül disfonksiyonu ile ilişkili midir?

Background: Insulin-like growth factor (IGF) is the primary mediator of growth hormone. IGF-1 may have an important role in protecting the myocardial functions following an acute myocardial infarction (AMI). Literature reveals only a limited number of studies investigating the relationship between the serum IGF-1/IGF binding protein-3 (IGFBP-3) levels and the left ventricular functions post AMI. We aimed to determine IGF-1 and IGFBP-3 levels and evaluate their effect on cardiac functions post AMI.Material and Method: Sixty five patients who were included in the study and the control group had 26 patients. Blood samples of the patients were obtained on the second day of their admission. The patients underwent echocardiographic examination on the 7th day of their hospitalization.Results: The serum IGF-1 and IGFBP-3 levels of the patient group were higher than those of the control group; however only IGF-1 levels were statistically significant (243,2±87,9 ng/mL versus 177,2±81,8 ng/mL p=0,001). The increase in the wall thickness and LV chamber size did not correlate with the decrease in LVEF and IGF-1/IGFBP-3 levels. The patients who had minor cardiac events had lower IGF-1 levels but this was not statistically significant (210.5±88.5 versus 253.1±86.1 p&amp;gt;0.05). Conclusion: IGF-1 and IGFBP-3 levels elevated following an the early AMI, but these markers were not correlated with the echocardiographical measurements in early post MI period.

Role of Cardiac Magnetic Resonance Imaging in Diagnosis of Myocardial Infarction

Introduction: Cardiac Magnetic Resonance Imaging provides an accurate and reproducible modality for the assessment of global ventricular volumes and function, and valuable in establishing a diagnosis of chronic and acute MI and distinguishing this condition from non-ischemic cardiomyopathies. Aim: To evaluate the role of cardiac Magnetic Resonance Imaging technique in diagnosis of myocardial infarction, assessment of myocardial viability. Subject and Method: The study was conducted over a period of 3 years at Assiut University Hospital. Fifty-six patients were recruited. All patients were subjected to full history taking and radiological evaluation using a 1.5-T MR system and echocardiography. Agreement regarding segmental wall motion was assessed by using Cohen’s Kappa statistics. Also ejection fraction measurement by both modalities was compared using bland-Altman plots. Agreement between Magnetic Resonance Imaging and conventional coronary angiography in detection of diseased coronary arteries was examined using Cohen’s kappa coefficient (κ). Results: It was found that ejection fraction detected by Echo were overestimated relative to Magnetic Resonance Imaging with statistically significant difference (p=0.004). While LV diameters detected by echocardiography were underestimated relative to Magnetic Resonance Imaging. Good agreement between Magnetic Resonance Imaging and Echo regarding segmental wall motion. There was positive very high correlation between the two modalities in evaluation of LV Functionality indices. Conclusion: CMR is superior to echo in evaluating left ventricular functionality indices with echo underestimating these indices except the ejection fraction which is overestimated by Echo. Moreover, CMR is better in evaluating post MI complications and associated cardiac abnormalities.