MI Patients Research Articles

Assay of macrotroponin I not complexed with troponin T: effect on the performance of troponin T to predict myocardial infarction

Abstract Background Cardiac troponin-immunoglobulin (Ig) complexes (macrotroponin) can interfere with cardiac troponin (cTn) test performance. However, the role of this interference has not been fully explored. We developed a specific, novel, 2-hour prototype immunoassay of monomer IgG-bound TnI (bTnI-IgG). Using this assay, our purpose was to examine the potential contribution of cTnT binding to macro-TnI, and report its effects on the clinical diagnostic and predictive performance of highly sensitive TnT (hs-TnT) and TnI (hs-TnI) assays. Methods Using the bTnI-IgG assay, we evaluated EDTA blood samples taken at presentation (t=0) from two ED acute chest pain studies; SPACE (n=1066) and FAST-TRAC (n=1440), with statistical analysis (logistic regression, ROC curves), to AMI and 1-year outcomes, alone and in combination, with hsTnT (Roche) and hsTnI (Abbott/Beckmann) tests. Pathway analysis was used to identify if single bTnI-IgG measurements improve risk stratification in low and high AMI risk. Results In individual and combined study datasets, bTnI-IgG concentrations in patients with adjudicated acute MI (n=336) were lower than all other diagnoses (p<0.001). Singularly, and in multivariable models containing hs-TnT or hs-TnI concentrations, bTnI-IgG was an independent predictor of MI. Amongst all patients with MI not ruled-out on presentation (hs-TnT >5ng/L) and not high-risk (hsTnT<14ng/L), the addition of bTnI-IgG to a model containing hs-TnT, HxMI and sex improved discrimination (AUC increase of 0.014 (95%CI: 0.004 to 0.025) from 0.788 to 0.802, p=0.009). Within a diagnostic pathway analyses of n=2126 matched patient data points, adding presentation bTnI-IgG measurement alone to an MI risk stratification model consisting of hs-TnT ≤URL, HxMI and sex yielded 14% more low risk patients identified (n=586 v 667 patients) through improved specificity (77% to 88%) whilst maintaining an overall sensitivity of >99%. bTnI-IgG also predicted 1-year mortality and new stroke in all patients (Odds Ratios 0.292 [95%CI 0.130 to 0.654] p=0.009) and 0.255 ([95%CI 0.078 to 0.834] p=0.024), respectively. Conclusions Measurement of bTnI-IgG that is free from cTnT could potentially improve ED presentation diagnostic test performance and risk stratification of MI patients using criteria that includes hs-TnT. No effects upon hs-TnI assays were observed. This data suggests current hs-TnT test design and measurements may be impacted by binding interactions between TnT and TnI. Finally, bTnI-IgG can independently predict mortality and stroke outcomes within 1 year of index presentation.

Standard modifiable risk factors and mortality in patients with ST-segment elevation myocardial infarction: findings from the FRENCHIE cohort

Abstract Background Improvements in the treatment of the 4 main standard modifiable cardiovascular (CV) risk factors (SMuRFs), hypertension (HTN), diabetes, hypercholesterolemia, and smoking, have led to better survival in patients with acute myocardial infarction (AMI). Recent large observational studies have reported that an increasing and sizable proportion of AMI patients have no SMuRF, and these SMURFless patients have (counterintuitively) worse outcomes than patients with at least one SMuRF. Purpose Using a French nationwide MI registry, we aimed to describe the proportion, characteristics and in-hospital mortality of ST-segment elevation MI (STEMI) patients according to the burden of SMuRFs. Methods The French Cohort of Myocardial Infarction Evaluation (FRENCHIE) is a large ongoing MI cohort, which collects data from all patients hospitalized for AMI < 48 h of symptom onset in 21 french centres. For the present analysis, patients with STEMI and without prior coronary artery disease (CAD) admitted in 2019 and 2020 were studied. SMuRFless patients were compared to patients with 1 SMuRF or ≥2 SMuRFs. Results Among 4692 STEMI patients, 986(21%) were SMuRFless, 2001(43%) had 1 SMuRF, and 1705(36%) had ≥2 SMuRFs . Among patients with SMuRFs, smoking (51.8%) and HTN (51.1%) were the most frequent SMuRF and HTN+hypercholesterolemia (10.3%) and HTN+smoking (8.3%) the most frequent SMuRFs associations. When compared with patients with 1 or ≥ 2 SMuRFs, SMuRFless patients were characterized by older age (64.1 vs 60.2 and 62.8 y, respectively), but lower rate of female sex (21.7 vs 22.2 and 26.2%, respectively), LVEF<40% (24.5 vs 26.7 and 26.2%), and lower admission CRP (14.8±38.3 vs 15.3±38.7 and 17.3±40.1 mg/L, respectively). There was a slight increase in BMI with increasing SMURFs (0 SMURF : 26±3.9 ; 1 SMuRF : 26.3±4.5 ; ≥2 SMuRFs : 28.0±5 kg/m²). As expected, SMuRFless patients were less frequently under chronic CV medications (7.9 vs 23.5 and 57.7%, respectively). However, acute STEMI medications were similar across the 3 groups. Crude in-hospital mortality showed a trend toward an increase with the number of SMuRFs (p = 0.123). By multivariate logistic regression analysis, the number of SMURFs was associated with increasing in-hospital mortality (Figure). In stratified analyses, the odds were similar for both sexes. Conclusion In French patients with an inaugural STEMI, one in 5 patient was SMURFless. The burden of risk factors was independently correlated to worse in-hospital survival. These observations emphasize the importance of standard RF on acute MI outcomes.SMuRF and in-hospital death(forest plot)

Abstract 18201: Intracoronary Optical Coherence Tomography versus Intravascular Ultrasound in ST and Non-ST Elevation Myocardial Infarction: A Nation-Wide Analysis

Introduction: Intravascular ultrasound (IVUS) and intracoronary optical coherence tomography (OCT) are the 2 techniques of intracoronary imaging that are currently accessible modalities to precisely measure coronary diameters and characterize morphology of lesions. We aimed to compare the impact of IVUS and OCT on outcomes and 30-day readmission rates following STEMI and NSTEMI. Methods: We queried the National Readmission database (2010-2019) to identify patients with STEMI and NSTEMI, undergoing PCI and compared outcomes and 30-day readmission rates between patients undergoing IVUS-guided PCI and OCT-guided PCI. Multivariable logistic regression was performed to evaluate the odds ratios (OR) of adverse outcomes in the 2 groups Results: Of 67,479 STEMI admissions undergoing ICI-guided PCI, 65,137 underwent IVUS and 2,342 underwent OCT. Patients undergoing OCT compared to IVUS had lower Length of stay (LOS) (OR 0.98 [0.96-0.99], P<0.05). However, there was no significant difference in in-hospital mortality, 30-day readmission rate and 90-day readmission rate. Of 103,901 NSTEMI admissions undergoing ICI-guided PCI, 100,127 underwent IVUS and 3774 underwent OCT. Patients undergoing OCT compared to IVUS had lower LOS (OR 0.95 [0.93-0.98], P<0.001) and 30-day readmission rates (OR 0.84 [0.71-0.99], P<0.05), but no significant differences were found in in-hospital mortality and 90-day readmission rates Conclusions: In acute MI patients undergoing ICI-guided PCI, OCT-guided PCI during index hospitalization is associated with similar outcomes compared to IVUS-guided PCI (except better LOS and 30-day readmission rates in NSTEMI).

Associations between ECG Changes and Echocardiographic Findings in Patients with Acute Non-ST Elevation Myocardial Infarction

Background: STEMI shows specific ECG changes due to sudden coronary blockage, but NSTEMI has varied ECG characteristics, including ST depressions and T wave inversions. Echocardiography, especially tissue Doppler imaging and speckle tracking, is crucial for diagnosing and predicting outcomes in acute coronary syndrome. The study aims to correlate ECG changes with echocardiographic findings in NSTEMI, offering potential diagnostic insights. Objective: The study aims to connect ECG alterations with echocardiographic findings in NSTEMI patients. Methods and Materials: This cross-sectional study took place from January to June 2023 at a Mymensingh Medical College Hospital, Mymensingh, Bangladesh. The research included 109 NSTEMI patients, both with and without cardiac history. Inclusion criteria were age above 30 and ischemic type of chest pain. Results: Out of 109 admitted patients, 67.4% were male and 6.4% were female. The average age was 54.34 ± 2.31 years, and prevalent conditions included 7.3% with diabetes, 11% with dyslipidemia, and 0.9% with edema, while 73% had a family history of ischemia. Conclusion: There were inconsistencies between the ECG and Echo in identifying the site of the infraction in the MI patients. Pulmonary hypertension, infection, ischemic stroke, and inferonasal regional wall motion abnormalities. Maximum no association was found in ECG changes and echocardiographic findings with acute non-ST elevation myocardial infarction.

68Ga]Ga-NODAGA-E[(cRGDyK)]2 angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure

BackgroundAngiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin αvβ3 is highly expressed in cells during angiogenesis and are therefore a promising target for imaging. In this study, we aimed to investigate the PET tracer [68Ga]Ga-RGD as a marker of angiogenesis following MI and its ability to predict cardiac functional parameters. MethodsFirst, the real-time interaction between [68Ga]Ga-RGD and integrin αvβ3 was investigated using surface plasmon resonance (SPR). Second, an animal study was performed to investigate the [68Ga]Ga-RGD uptake in the infarcted area after one and four weeks following MI in a rat model (MI = 68, sham surgery = 36). Finally, the specificity of the [68Ga]Ga-RGD tracer was evaluated ex vivo using histology, autoradiography, gamma counting and flow cytometry. ResultsSPR showed that [68Ga]Ga-RGD has a high affinity for integrin αvβ3, forming a strong and stable binding. PET/CT showed a significantly higher uptake of [68Ga]Ga-RGD in the infarcted area compared to sham one week (p < 0.001) and four weeks (p < 0.001) after MI. The uptake of [68Ga]Ga-RGD after one week correlated to end diastolic volume (r = 0.74, p < 0.001) and ejection fraction (r = − 0.71, p < 0.001) after four weeks. ConclusionThis study demonstrates that [68Ga]Ga-RGD has a high affinity for integrin αvβ3, which enables the evaluation of angiogenesis and remodeling. The [68Ga]Ga-RGD uptake after one week indicates that [68Ga]Ga-RGD may be used as an early predictor of cardiac functional parameters and possible development of heart failure after MI. These encouraging data supports the clinical translation and future use in MI patients.

Disease trajectories following myocardial infarction: insights from process mining of 145 million hospitalisation episodes

Knowledge of post-myocardial infarction (MI) disease risk to date is limited-yet the number of survivors of MI has increased dramatically in recent decades. We investigated temporally ordered sequences of all conditions following MI in nationwide electronic health record data through the application of process mining. We conducted a national retrospective cohort study of all hospitalisations (145,670,448 episodes; 34,083,204 individuals) admitted to NHS hospitals in England (1st January 2008-31st January 2017, final follow-up 27th March 2017). Through process mining, we identified trajectories of all major disease diagnoses following MI and compared their relative risk (RR) and all-cause mortality hazard ratios (HR) to a risk-set matched non-MI control cohort using Cox proportional hazards and flexible parametric survival models. Among a total of 375,669 MI patients (130,758 females; 34.8%) and 1,878,345 matched non-MI patients (653,790 females; 34.8%), we identified 28,799 unique disease trajectories. The accrual of multiple circulatory diagnoses was more common amongst MI patients (RR 4.32, 95% CI 3.96-4.72) and conferred an increased risk of death (HR 1.32, 1.13-1.53) compared with matched controls. Trajectories featuring neuro-psychiatric diagnoses (including anxiety and depression) following circulatory disorders were markedly more common and had increased mortality post MI (HR ranging from 1.11 to 1.73) compared with non-MI individuals. These results provide an opportunity for early intervention targets for survivors of MI-such as increased focus on the psychological and behavioural pathways-to mitigate ongoing adverse disease trajectories, multimorbidity, and premature mortality. British Heart Foundation; Alan Turing Institute.

Rivaroxaban attenuates neutrophil maturation in the bone marrow niche

Pharmacological inhibition of factor Xa by rivaroxaban has been shown to mediate cardioprotection and is frequently used in patients with, e.g., atrial fibrillation. Rivaroxaban's anti-inflammatory actions are well known, but the underlying mechanisms are still incompletely understood. To date, no study has focused on the effects of rivaroxaban on the bone marrow (BM), despite growing evidence that the BM and its activation are of major importance in the development/progression of cardiovascular disease. Thus, we examined the impact of rivaroxaban on BM composition under homeostatic conditions and in response to a major cardiovascular event. Rivaroxaban treatment of mice for 7 days markedly diminished mature leukocytes in the BM. While apoptosis of BM-derived mature myeloid leukocytes was unaffected, lineage-negative BM cells exhibited a differentiation arrest at the level of granulocyte–monocyte progenitors, specifically affecting neutrophil maturation via downregulation of the transcription factors Spi1 and Csfr1. To assess whether this persists also in situations of increased leukocyte demand, mice were subjected to cardiac ischemia/reperfusion injury (I/R): 7 d pretreatment with rivaroxaban led to reduced cardiac inflammation 72 h after I/R and lowered circulating leukocyte numbers. However, BM myelopoiesis showed a rescue of the leukocyte differentiation arrest, indicating that rivaroxaban's inhibitory effects are restricted to homeostatic conditions and are mainly abolished during emergency hematopoiesis. In translation, ST-elevation MI patients treated with rivaroxaban also exhibited reduced circulating leukocyte numbers. In conclusion, we demonstrate that rivaroxaban attenuates neutrophil maturation in the BM, which may offer a therapeutic option to limit overshooting of the immune response after I/R.

Interleukin-34-NF-κB signaling aggravates myocardial ischemic/reperfusion injury by facilitating macrophage recruitment and polarization

Macrophage infiltration and polarization are integral to the progression of heart failure and cardiac fibrosis after ischemia/reperfusion (IR). Interleukin 34 (IL-34) is an inflammatory regulator related to a series of autoimmune diseases. Whether IL-34 mediates inflammatory responses and contributes to cardiac remodeling and heart failure post-IR remains unclear. IL-34 knock-out mice were used to determine the role of IL-34 on cardiac remodeling after IR surgery. Then, immunofluorescence, flow cytometry assays, and RNA-seq analysis were performed to explore the underlying mechanisms of IL-34-induced macrophage recruitment and polarization, and further heart failure after IR. By re-analyzing single-cell RNA-seq and single-nucleus RNA-seq data of murine and human ischemic hearts, we showed that IL-34 expression was upregulated after IR. IL-34 knockout mitigated cardiac remodeling, cardiac dysfunction, and fibrosis after IR and vice versa. RNA-seq analysis revealed that IL-34 deletion correlated negatively with immune responses and chemotaxis after IR injury. Consistently, immunofluorescence and flow cytometry assays demonstrated that IL-34 deletion attenuated macrophage recruitment and CCR2+ macrophage polarization. Mechanistically, IL-34 deficiency repressed both the canonical and noncanonical NF-κB signaling pathway, leading to marked reduction of P-IKKβ and P-IκBα kinase levels; downregulation of NF-κB p65, RelB, and p52 expression, which drove the decline in chemokine CCL2 expression. Finally, IL-34 and CCL2 levels were increased in the serum of acute coronary syndrome patients, with a positive correlation between circulating IL-34 and CCL2 levels in clinical patients. In conclusion, IL-34 sustains NF-κB pathway activation to elicit increased CCL2 expression, which contributes to macrophage recruitment and polarization, and subsequently exacerbates cardiac remodeling and heart failure post-IR. Strategies targeting IL-34-centered immunomodulation may provide new therapeutic approaches to prevent and reverse cardiac remodeling and heart failure in clinical MI patients after percutaneous coronary intervention. This study was supported by the National Nature Science Foundation of China (81670352 and 81970327 to R T, 82000368 to Q F).

Torsades De Pointes Complicating Acute Myocardial Infarction, Twisting the Prognosis

Introduction Torsades de pointes (TdP), a form of polymorphic ventricular tachycardia that manifests in the setting of an acquired or congenital QT interval prolongation. Polymorphic VT can occur in hyper acute phase or healing phase of an acute myocardial infarction. The presence of necrotic area caused by the infarction explains the existence of a possible circuit as well as the appearance of a re-entry arrhythmia. Aims and Objectives Our aim is to study the incidence of long Qt induced TdP in acute MI patients and its prognostic implications. We also want to analyze the impact of primary percutaneous transluminal coronary angioplasty in the management of these subset of patients. Methods In this cross-sectional observational study done from May 2021 to May 2022, We have studied 320 cases of acute MI, of which 6 were found to have TdP (1.9%). Four patients had inferior wall myocardial infarction and 2 patients had Non-ST elevation MI. Thrombolysis was done in 2 cases. Two cases underwent primary angioplasty. One case was recommended for coronary artery bypass grafting. All cases underwent appropriate electrolyte correction, besides cardioversion, as needed. Results All patients with TdP had prolonged QT interval. 50% of patients had mild hypokalemia. Two patients had complete heart block. Three patients had severe left ventricular dysfunction. Patients who underwent primary angioplasty survived. Thrombolysis had less impact on survival in Acute Mi with TdP. Conclusion Early percutaneous coronary angioplasty, combined with electrolyte correction, improves the prognosis in TdP complicating acute MI.

The effect of trehalose administration on the serum expression levels of microRNAs associated with lipid metabolism and autophagy process in patients with myocardial infarction - the post-hoc analysis of the TREAT-IR trial.

IntroductionThis study aimed to evaluate the TRE-induced changes in the serum expression levels of miRNAs associated with lipids metabolism and autophagy process in MI patients to assess the potential protective effects of TRE in these patients.Material and methodsThis post hoc investigation was performed on serum samples obtained from a pilot randomized, double blind, placebo-controlled clinical trial that recruited 14 men (aged 18-80) who had MI and systemic inflammation. The patients were randomized in a 2:1 ratio to either TRE (15 g/week, intravenous (IV) ad-ministration) (N=10) or placebo groups (equal volume of saline 0.9 %) (N=4) for a period of 12 weeks. To measure the relative serum expression levels of miRNA-155, miRNA-221, and miRNA-33, the SYBR Green qPCR method was used.ResultsmiRNA-155 showed significantly higher serum expression levels in the TRE group (2.772±0.73; P=0.009) when compared to the placebo group. Also, significant reductions in miRNA-155 (0.171±0.03; P=0.016), miRNA-221 (0.116±0.07; P=0.013), and miRNA-33a (0.076±0.07; P=0.025) were observed in the placebo group at the end of the study. Nevertheless, the reduction (normalized to the baseline) of the serum expres-sion levels of miRNA-221 (FC:0.87±0.20 vs FC:0.18±0.08; P=0.009) and miRNA-33a (FC:0.73±0.22 vs FC:0.13±0.08; P=0.025) were significantly less in TRE group than in the placebo group.ConclusionsIV TRE administration did not reduce the expression of miRNA-221 and miRNA33a as much as placebo. Keeping a steady state of the serum expression levels of these miRNAs associated with lipoproteins metabolism and autophagy in the TRE group might have protective effects in patients with MI.

Platelet miRNAs: differential expression in coronary artery disease and associations with course of left ventricular systolic function

BackgroundMicroRNAs are paramount in post transcriptional gene regulation. We investigated platelet miRNAs in patients with CAD and examined potential associations with course of left ventricular ejection fraction (LVEF%).Materials and methodsIn a first cohort, 62 MiRNAs were measured in platelets of 100 patients suffering from CAD. Expression profiles of individuals with chronic coronary syndrome (CCS) and MI were compared (CCS n = 67, MI n = 33). Also, associations between miRNA profiles and change in left ventricular ejection fraction (LVEF%) were investigated. In a second cohort of patients suffering from CCS (n = 10), MI (n = 11) or no CAD (n = 13), we measured miRNA expression in platelets, platelet supernatant and serum. This was carried out before and after in vitro platelet activation with CRP.ResultsPlatelet miRNAs 103a-3p and 155-5p demonstrated higher expression in patients with CCS then in individuals with MI. Furthermore, multiple miRNAs were significantly higher expressed in matched controls compared to MI patients. 8 miRNAs showed higher expression in patients with improving LVEF% after a 1-year follow-up. In our second cohort, we found higher concentrations of 6 miRNAs in the platelet supernatant of patients with CCS, MI and no CAD after in vitro platelet activation. Most of these miRNAs showed a higher abundance in serum of MI patients as compared to CCS.ConclusionSeveral miRNAs show higher expression in platelets of CCS compared to MI. After in vitro platelet activation, a release of multiple miRNAs out of the thrombocyte was observed. Furthermore, upregulation of serum miRNAs was found in MI patients when compared to CCS patients and individuals without CAD. Hence, platelets could present a source of upregulated circulating miRNAs in MI and additionally affect course of LVEF%.

Individualized assessment and optimization of post myocardial infarction care by introducing a hybrid clinic - A DGH experience

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Optimal secondary prevention remains key in improving cardiovascular outcomes post myocardial infarction. Barriers to achieving timely and individualized medical optimization include unavailability of close follow up’s, compliance to secondary prevention, and more recently, the impact of COVID pandemic on outpatient face to face clinic appointments. With the recent emphasis from the European Society of Cardiology on secondary prevention in addition to optimizing lipid therapy, a dedicated service for post MI patients to address individualized risks can provide a timely opportunity to improve holistic cardiovascular care. Purpose To assess established secondary prevention practices, we initially audited 52 patients who presented with ACS between Jan 2020 and July 2020. These patients were assessed for post MI care optimization at 6 weeks post discharge. Utilizing ESC guidelines as audit targets, in our 6-week post discharge audit, we identified that there was scope of ACE-inhibitor up titration in 55.8% of the patients, beta-blocker optimization in 9.6%, Lipid lowering agents in 15.4%, mineralocorticoid receptor antagonist addition in patients with impaired LV systolic function in 5.8% of the patients. 5% of patients with new diagnosis of diabetes required referral to specialist teams for diabetic medication initiation or optimization. These results provided an opportunity to introduce a structured post MI clinic that will allow individualized risk assessment on an outpatient basis. Method We proposed a one stop hybrid clinic where all patients discharged following a myocardial infarction received a consultation 6 – 8 weeks following a discharge. These patients were sent blood forms 2-3 weeks prior to their appointment for full blood count levels, renal functions, liver profile, HBa1c levels and lipid profile. Focus of this consultation was to assess and educate the patient on risk factors (smoking, diabetes, cardiac rehab program), assess and address compliance to secondary prevention medications and finally titrate medications to maximum tolerated doses whilst achieving ESC defined targets for secondary prevention (post MI target systolic BP&amp;lt;140mmHg in non diabetics and &amp;lt;130mmHg in diabetics, LDLc &amp;lt;1.4, smoking cessation, HBa1c &amp;lt;49). Where appropriately identified, referral to lipid specialist and diabetes specialist teams were made to provide holistic multi-disciplinary management. Results To understand the Impact made by the clinic we obtained patient list through local electronic records to filter those discharged with a primary diagnosis of myocardial infarction in 2022. An audit tool was created and data collection was performed including baseline characteristics as per table 1 and interventions made Table 2. Conclusion(s) By establishing the post MI clinic we were able to demonstrate efficient individualized assessment and optimization of secondary prevention risk factors and pharmacotherapy.

Low-dose dobutamine infusion and single-dose tocilizumab in acute myocardial infarction patients with high risk of cardiogenic shock development - rationale and design of the DOBERMANN trial

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Fonden Background Cardiogenic shock (CS) is seen in up to 10% of patients with ST-elevation myocardial infarction (STEMI) and is associated with a high mortality rate of up to 50%. Approximately 1/3 of STEMI-patients developing CS are not in overt shock at time of hospital admission but will develop hemodynamical instability within the following hours to days. Patients at risk of CS development may be clinically stable but with normal lactate levels (Society for Cardiovascular Angiography and Interventions classification, SCAI A/B). The Observatoire Régional Breton sur l'Infarctus (ORBI) clinical risk score has recently been developed and validated for predicting the risk of in-hospital (late) CS. STEMI-patients with an ORBI score &amp;gt;=10 have a risk of in-hospital CS development of more than 8-10%. NTproBNP is a biomarker released from the myocardium reflecting neurohormonal activation which is strongly correlated with hemodynamic parameters. Neurohormonal activation as well as a systemic inflammatory response are present acutely at hospital admission in STEMI patients developing late CS compared to non-CS patients suggesting an early subclinical hemodynamic deterioration. Dobutamine induces significant positive inotropic- and dose-dependent chronotropic effects and decreases afterload by peripheral vasodilatation, which increases cardiac output and organ perfusion. The interleukin-6 receptor antagonist Tocilizumab has been shown to reduce troponin leakage and increase myocardial salvage in acute MI patients. The effects of Dobutamine and Tocilizumab in a high-risk population have not previously been investigated. Methods DOBERMANN is an investigator-initiated, double blinded randomized clinical trial. Consecutive patients with acute MI admitted for acute coronary angiography and treated with percutaneous coronary intervention are screened with the ORBI risk score in the catheterization laboratory. One hundred adult patients presenting without CS at hospital admission with an intermediate-high risk of CS development (ORBI risk score of &amp;gt;=10) will be randomized 2x2 to receive a continuous intravenous infusion of dobutamine (5 micrograms/kg/minute, 24h) vs. placebo, and a single dose of Tocilizumab (280 mg, 1h) vs. placebo. NTproBNP as a proxy for development of CS and hemodynamic instability will be sampled for primary endpoint analysis. Effects on clinical parameters, mortality, morbidity as well as specific indicators of inflammation, cardiac function, and infarct size will secondarily be assessed noninvasively at 48h and at three months follow-up. Enrollment began in March 2022 and is commencing as planned. Discussion We hypothesize that inflammatory and neurohormonal responses are associated with subclinical hemodynamic instability in patients with AMI with intermediate/high risk of CS. The potentially unstable condition may be targeted pharmacologically as an add-on to existing therapy.

Kompanse Böbrek Yetmezlikli Hastalarda Koroner Bypass Morbiditesini Azaltan bir Teknik; Peroperatif Ultrafiltrasyon

INTRODUCTION: Preoperative renal dysfunction is one of the most important risk factors affecting postoperative morbidity and mortality in patients undergoing cardiac surgery. While patients with end-stage renal disease and dialysis-dependent constitute 1-3% of the renal failure spectrum, it should not be forgotten that coronary revascularization surgery is performed at a rate of 2-5% in the remaining asymptomatic majority. However, an optimal perioperative strategy has not been developed for this group of patients who have not yet undergone hemodialysis. In our study, conventional ultrafiltration was applied with a modified peroperative heart-lung machine and it was aimed to decrease mortality and morbidity. METHOD: 6303 patients who underwent coronary bypass surgery with the cardiopulmonary bypass technique between 2004 and 2011 at Başkent University Adana Hospitals were examined, and 99 patients with a preoperative serum creatinine level higher than 1.5 mg/dl were included in this retrospective study. 99 patients were divided into two groups as UF performed (35) and not performed (64); They were evaluated in terms of drainage amounts, length of hospital stay, early/late mortality and morbidity, and newly developing dialysis needs. RESULTS: There was no significant difference between the groups in terms of post-operative hemodialysis need, length of hospital stay and major complications. However; Peroperative ultrafiltration in obese, diabetic, recent MI, COPD and congestive heart failure patients; postoperatively less inotrope (P=0.0001), less diuretic requirement (P=0.0001), less colloidal fluid replacement (p=0.009), and relatively fewer minor complications. DISCUSSION AND CONCLUSION: Ultrafiltration to be applied during cardiopulmonary bypass in order to create a more balanced intravascular volume in patients with compensated renal failure, to reduce the need for volume expander fluid used for this purpose, to remove inflammation mediators that occur during cardiopulmonary bypass, and therefore to protect renal functions without the need for additional medication, especially COPD. We recommend it in the diabetic and obese patient group.

PECULIARITIES OF CONNECTIVE TISSUE METABOLISM IN PATIENTS WITH POST-INFARCTION REMODELING AND REPERFUSION SYNDROME

Early restoration of coronary blood flow in acute myocardial infarction with elevation helps reduce the area of myocardial necrosis, prevent dilatation of the ventricular cavity, and reduce the development of arrhythmias and mortality. However, despite modern technologies in STEMI treatment, the development of reperfusion syndrome, in particular, arrhythmias, is possible after the restoration of blood flow in the infarct-related artery, which is a consequence of acute cellular, metabolic and local electrophysiological changes in the myocardium.&#x0D; The aim: is to investigate the long-term effects of reperfusion syndrome on the catabolic/anabolic activity of connective tissue and the processes of connective tissue framework formation in the post-infarction period in patients with myocardial infarction.&#x0D; Materials and methods. The study involved 156 patients with acute myocardial infarction with ST segment elevation (STEMI), and 15 apparently healthy individuals (control of laboratory parameters). The average age of the patients was (57.8±1.2) years. The percent of male patients prevailed (76 %).&#x0D; All MI patients were divided into two groups: Group I (98 people) – MI patients without clinical signs of reperfusion syndrome during revascularization, Group II (58 people) – MI patients with the signs of reperfusion syndrome in the form of rhythm and conductivity disturbances during revascularization of coronary arteries by percutaneous coronarography intervention (PCI) with prolonged stenting of the infarct-dependent coronary artery.&#x0D; Peculiarities of connective tissue metabolism were studied by the content of free and bound oxyproline, glycosaminoglycans, and antibodies to atypical collagens (Ig M and Ig G) in blood serum.&#x0D; Results. The recovery period after myocardial infarction showed an increase in collagen catabolism over collagen synthesizing processes in patients with MI who had reperfusion syndrome. The described patterns were also established by changes in glycosaminoglycans. The study showed an increase in the level of antibodies to atypical collagens. Particularly, the level of Ig M, which was within the norm (0.43±0.18) ng/ml, in patients with MI without reperfusion manifestations was three times higher (p&lt;0.001), and in cases of combination of MI and reperfusion syndrome – the highest (p&lt;0.001).&#x0D; Conclusions:&#x0D; &#x0D; Changes in collagen-synthesizing processes are observed in patients with MI, with a tendency to increase the processes of catabolism of the connective tissue matrix.&#x0D; The presence of reperfusion syndrome manifestations in MI patients after revascularization aggravates the processes of catabolism, even in the recovery period after MI.&#x0D; Increase in the activity of catabolic processes stimulates fibrosis and formation of rigid matrix and atypical collagen, to which antibodies are synthesized, thus blocking the pathological circuit of restructuring of the heart connective tissue framework, and accordingly its pathological remodeling.&#x0D; The obtained study results contribute to the identification of more sophisticated approaches to revascularization techniques to avoid negative effects of reperfusion syndrome, as well as new effective medications for collagen synthesis correction, which can increase the effectiveness of rehabilitative management of such&#x0D;

Is Vitamin D Deficiency &amp; Increased BMI – An Independent Risk Factor of MI? - A Comparative Analysis among MI Patients

Background: Cardiovascular diseases (CVD) are the commonest cause of mortality and morbidity worldwide. Despite the rising proportions of CAD, only limited data are available on the relationship between Vitamin D. This study was aimed to assess the serum levels of 25(OH) Vitamin D and its causal association of Vitamin D deficiency as an independent risk factor in patients with Acute ST-Elevation Myocardial Infarction in National Institute of Medical Sciences and Research, Jaipur, Rajasthan. Material and Methods: Patients admitted with acute ST- Elevation and NON-ST- Elevation Myocardial Infarction in the CCU unit of the National Institute of Medical Science &amp; Research, Jaipur were chosen as cases. Rest healthy same age and sex-match ambulatory subjects were kept as controls. The data entered in the MS EXCEL spreadsheet and analysis will be done using Statistical Package for Social Sciences (SPSS) version 23.0. Continuous variables were presented as mean ± SD. Categorical variables were expressed as frequencies and percentages. The Chi-square test of association or Fischer exact test has been used to determine if there is an association between two categorical variables. Results: Among 50 study cases, the prevalent age group where 50-60 years was 16(32%) followed by 40-50 years (28%) while in control the majority of the participants were in between 40-50 years, 16(32%) followed by 15 cases (30%) in 30-40 years. It was observed that the mean BMI of the study cases was 29.11 ± 3.1 and for controls was 24.41 ± 1.92. Fifty-four percent of cases were found overweight with a BMI range between 25-29.9 and 21(42%) were found obese. In considering the control group, 21(42%) subjects were found overweight with a BMI range between 25-29.9 while no subject was obese with above 30. Most of the cases with vitamin deficiency and vitamin insufficiency were either overweight or obese and had BMI above 25 and a statistically significant difference with p=0.02828. ......

Sex Differences in Outcome and Prescribing Practice in ST-elevation MI Patients with Multivessel Disease and Incomplete Revascularisation.

Objective: To investigate the extent to which multivessel disease, incomplete revascularisation and prescribing differences contribute to sex-based outcome disparities in patients with ST-elevation MI (STEMI) and establish whether differences in cardiac death and MI (CDMI) rates persist at long-term follow-up. Methods and results: This observational study evaluates sex-based outcome differences (median follow-up 3.6 years; IQR [2.4-5.4]) in a consecutive cohort of patients (n=2,083) presenting with STEMI undergoing percutaneous coronary intervention). Of the studied patients 20.3% (423/2,083) were women and 38.3% (810/2,083) had multivessel disease (MVD). Incomplete revascularisation was common. The median residual SYNTAX score (rSS) was 5.0 (IQR [0-9]) in women and 5.0 (IQR [1-11]) in men (p=0.369), and in patients with MVD it was 9 (IQR [6-17]) in women and 10 (IQR [6-15]) in men (p=0.838). The primary endpoint CDMI occurred in 20.3% of women (86/423) and in 13.2% of men (219/1,660) (p=0.028). Differences persisted following multivariable risk adjustment: female sex was independently associated with CDMI (aHR 1.33; IQR [1.02-1.74]). Women with MVD had CDMI more often than all other groups (p<0.001 for all). Significant sex-based prescribing differences were evident: women were less likely to receive guideline-recommended potent P2Y12 inhibitors than men (31% versus 43%; p=0.012), and differences were particularly evident in patients with MVD (25% in women versus 45% in men, p=0.011). Conclusion: Sex-based differences in STEMI patient outcome persist at long-term follow-up. Poor outcomes were disproportionately found in women with MVD and those with rSS>8. Observed differences in P2Y12 prescribing practices may contribute to poor outcomes for women with MVD and incomplete revascularisation.

Wearable cardioverter defibrillator for preventing sudden cardiac death in patients at risk: An updated systematic review of comparative effectiveness and safety.

To synthesise the available evidence of wearable cardioverter defibrillator (WCD) therapy as an add-on measure to optimal medical therapy (OMT) or as a replacement of hospital stay. An update systematic review (SR) of comparative effectiveness and safety of WCD therapy was conducted. We included randomised controlled trials (RCT), prospective comparative studies and prospective uncontrolled studies with at least 100 patients. A narrative synthesis of the evidence was conducted. One RCT (n = 2348) and further eleven observational studies (n = 5345) fulfilled our inclusion criteria. In the only available RCT, the use of the WCD was not statistically associated with a clinical benefit on arrhythmic mortality in post-myocardial infarction (MI) patients with an ejection fraction of ≤35%. The compliance with WCD therapy was low in the RCT and high in observational studies, with ten observational studies reporting on a daily wear time between 20 and 23.5 h. The range of percentage of patients receiving at least one appropriate shock was 1-4.8% and the rate of first shock success was reported to be 100% in three studies. Serious adverse events (SAEs) such as inappropriate shocks occurred rarely, with between 0% and 2% of patients being inappropriately shocked within ten observational studies. In one of the observational studies, two patients (2%) were allergic to nickel developing skin rash and false alarms occurred in 58 patients (57%) in this study. Another registry study (n = 448) reported milder AEs, such as dermatitis and pressure marks, occurring in 0.9% and 0.2% of enrolled patients, respectively. The only available RCT failed to show superiority of add-on use of WCD in post MI patients. Observational evidence shows that the compliance with WCD is good, but the evidence is afflicted with selection bias and the inclusion of diverse mixed patient populations diluting the ability to draw indication-specific conclusions on the utility of the device. More comparative data is needed to justify continuing or expanding use of WCD therapy.

Investigation into miRNA profile in patient groups with and without ST elevation

Abstract Objectives Because acute myocardial infarction (AMI) may occur suddenly and cannot be predicted, it is critical to identify early diagnosis markers. In recent years, in addition to the developing diagnostic methods, other markers that may be related to the diagnosis of AMI are miRNA molecules. The specificity of miRNAs involved in the pathogenesis of atherosclerosis and regulation of cardiac functions has been shown. The present study aimed to investigate the changes in miRNA expression levels in MI patients with ST-elevation (STEMI) and without ST elevation (NSTEMI). Methods In this study, 25 patients with STEMI, 25 with NSTEMI, and 20 healthy participants were included. Expression analysis of miRNAs isolated from the plasma of individuals was performed using high-throughput real-time PCR. Results Compared with the control group, miR-221-3p and miR-30d-5p were downregulated, while miR-25-3p, miR-92a-3p, miR-34a-5p and miR-150 upregulated in the patient group with NSTEMI; miR-221-3p, miR-25-3p, miR-30d-5p and miR-92a-3p were downregulated while miR-208a-3p was upregulated in patients with STEMI (p&gt;0.05). Conclusions In conclusion, miRNAs may be an early biomarker for diagnosing AMI; however, further and larger studies are needed.

Clinical Features and Long-Term Outcomes in Very Young Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries

Background and Aim: The most common cause of acute coronary syndrome (ACS) is the erosion causing the development of atherosclerotic plaque. There is, however, a subset of individuals with ACS-like symptoms but no significant coronary artery obstruction characterized as myocardial infarction with non-obstructive coronary arteries (MINOCA). The purpose of the present study was to assess the clinical features and long-term outcome of young MI patients with non-obstructive coronary arteries. Patients and Methods: This prospective observational study was carried out on 926 patients underwent coronary angiographies in the Cardiology Department of Medical Teaching Institute (MTI) Lady Reading Hospital, Peshawar from January 2019 to December 2022. All the patients (age ≤45 years) with suspected acute coronary syndrome were enrolled. Participants were categorized into three groups: Group-I [obstructive coronary artery disease (o-CAD)], Group-II (MINOCA diagnosed patients), and Group-III [control (non-coronary artery disease)]. Demographic details, clinical features, and outcomes of patients were recorded. Results: Of the total 926 patients underwent coronary angiographies, about 122 (13.2%) patients were ≤45 years old. Out of 122 patients, the incidence of o-CAD, MINOCA, and control (non-coronary artery disease) was 60.7% (n=74), 13.1% (n=16), and 26.2% (n=32) respectively. Chest pain was the most prevalent symptom found in 95.1% (n=116) group-I, 93.8% (n=15) in group-II, and 81.3% (n=26) respectively. MINOCA patients had similar high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels with o-CAD patients, however, the triglyceride values was significantly higher (180.8±90.6) than control (136.2±82.8). Conclusion: The present study found that MINOCA and o-CDA group patients had similar long-term poor outcomes. Triglyceride levels, depression, BMI &gt;30 kg/m2, and family history of CAD are significant risk factors for MINOCA during follow-up. Secondary preventive initiatives are required in these patients to avoid recurrences and enhance outcomes. Keywords: CAD, MINOCA, Young patients, Clinical features, Long-term outcomes