Large Myocardial Infarction Research Articles

Granulocyte colony-stimulating factor for stem cell mobilisation in acute myocardial infarction: a randomised controlled trial

BackgroundTo determine whether granulocyte colony-stimulating factor (G-CSF) improves clinical outcomes after large ST-elevation myocardial infarction (STEMI) when administered early in patients with left ventricular (LV) dysfunction after successful percutaneous coronary...

Association between peak troponin level and prognosis among patients admitted to intensive cardiovascular care unit

IntroductionHigh-sensitivity cardiac troponin (hs-cTn) is a key biomarker for myocardial injury, yet its prognostic value in intensive cardiovascular care units (ICCU) remains poorly understood. We aimed to assess the association between peak hs-cTn levels and prognosis in ICCU patients. MethodsAll patients admitted to a tertiary care center ICCU between July 2019 – July 2023 were prospectively enrolled. Patients were divided into five groups according to their peak hs-cTnI levels: A) hs-cTnI <100 ng/L; B) hs-cTnI of 100–1000 ng/L; C) hs-cTnI of 1000–10,000 ng/L; D) hs-cTnI of 10,000–100,000 ng/L and E) hs-cTnI ≥100,000 ng/L. The primary outcome was all-cause mortality at one year. ResultsA total of 4149 patients (1273 females [30.7 %]) with a median age of 69 (IQR 58–79) were included. Group E was highly specific for myocardial infarction (97.4 %) and especially for ST segment elevation myocardial infarction (STEMI) (87.5 %). Patients in group E were 56 % more likely to die at 1-year in an adjusted Cox model (95 % CI 1.09–2.23, p = 0.014) as compared with group A. Subgroup analyses revealed that among STEMI patients, higher peak hs-cTnI levels were not associated with higher mortality rate (HR 1.04, 95 % CI 0.4–2.72, p = 0.9), in contrast to patients with NSTEMI (HR 7.62, 95 % CI 1.97–29.6, p = 0.003). ConclusionsPeak hs-cTnI levels ≥100,000 ng/L were linked to higher one-year mortality, largely indicative of large myocardial infarctions. Notably, the association between elevated hs-cTnI levels and mortality differed between STEMI and NSTEMI patients, warranting further investigation.

A CASE REPORT OF AN ASYMPTOMATIC PATIENT WITH TYPE 2 WELLENS’ SYNDROME AND RENAL CARCINOMA

Abstract A 65–year–old male with renal cell carcinoma, previously treated with nephrectomy and recently diagnosed with lung metastases, presented to the cardiology clinic for investigations before starting chemotherapy. He reported a history of ischemic heart disease, a non–ST–elevation myocardial infarction for which he refused coronary angiography in 2005, and a negative maximal stress test for ischemia in 2017. Additionally, the patient reported insulin–dependent type 2 diabetes mellitus and well–controlled arterial hypertension. The patient was referred for a cardiological evaluation due to a reported short–term rhythmic heartbeat without other cardiological symptoms. Cardiological parameters were stable (blood pressure: 140/95 mmHg; heart rate: 42 bpm, and oxygen saturation without oxygen supplementation: 98%). Physical examination was normal. Laboratory investigations did not show elevated levels of high–sensitivity troponin I, and only signs of mild chronic kidney disease were observed. The initial ECG showed sinus bradycardia with deeply inverted T–waves in the extended anterior area (Fig. 1), which were not present in an ECG performed one month earlier. There was no reported chest pain. An echocardiogram examination demonstrated hypertensive heart disease with marked hypokinesia of the mid–apical portion of the anterior wall and anterior interventricular septum, together with a moderate reduction in global systolic function (LV ejection fraction: 40%). The patient was hospitalized, and underwent coronary angiography the following day. He had a low–risk score (GRACE: 95 pts) As shown in Fig. 2, there was evidence of long sub–occlusive stenosis of the proximal part of the anterior descending coronary artery that was treated with angioplasty and a single drug–eluted stent placement, resulting in a good angiographic result. After the procedure, there was a rapid recovery of regional kinetics but a slower normalization of the electrocardiographic morphology (Fig. 3). Comment Wellens‘ syndrome identifies a particular subtype of unstable angina characterized by the appearance of ischemic changes on the ECG,. The clinical risk assessment of this subgroup of patients with ACS, apparently having a more benign prognosis due to their definition as unstable angina with a low GRACE risk score, potentially has an evolution toward a large myocardial infarction if not promptly diagnosed.

Wellens Syndrome the Previous Room to A Large Previous Myocardial Infarction. Report of A Case.

Wellens syndrome or also called anterior descending T wave syndrome, described for the first time in 1982 by Wellens and Zwaan, as a subtype of high-risk unstable angina that progresses to myocardial infarction in the anterior face, which can be massive and fatal; Documentation of this pattern on the ECG would be essential to initiate pharmacological treatment and priority referral to the hemodynamics room; A case of a 74-year-old male patient is described who begins symptoms in the early morning with typical chest pain and adrenergic discharge that progressively disappears. The patient is sent to a High Specialty Medical Center for Catheterization, which correlates injury in a rare anatomical site of the middle segment of the anterior descending artery. Knowledge of Wellens Syndrome in the emergency room is of utmost importance to reduce morbidity in patients and avoid its consequences, as well as the importance of primary referral for cardiac catheterization.

Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction

BackgroundMost trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin–angiotensin–aldosterone system antagonists.MethodsIn a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction.ResultsFrom September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no–beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P=0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no–beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no–beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%.ConclusionsAmong patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.)

Neutrophils are indispensable for adverse cardiac remodeling in heart failure

Persistent immune activation contributes significantly to left ventricular (LV) dysfunction and adverse remodeling in heart failure (HF). In contrast to their well-known essential role in acute myocardial infarction (MI) as first responders that clear dead cells and facilitate subsequent reparative macrophage polarization, the role of neutrophils in the pathobiology of chronic ischemic HF is poorly defined. To determine the importance of neutrophils in the progression of ischemic cardiomyopathy, we measured their production, levels, and activation in a mouse model of chronic HF 8 weeks after permanent coronary artery ligation and large MI. In HF mice, neutrophils were more abundant both locally in failing myocardium (more in the border zone) and systemically in the blood, spleen, and bone marrow, together with increased BM granulopoiesis. There were heightened stimuli for neutrophil recruitment and trafficking in HF, with increased myocardial expression of the neutrophil chemoattract chemokines CXCL1 and CXCL5, and increased neutrophil chemotactic factors in the circulation. HF neutrophil NETotic activity was increased in vitro with coordinate increases in circulating neutrophil extracellular traps (NETs) in vivo. Neutrophil depletion with either antibody-based or genetic approaches abrogated the progression of LV remodeling and fibrosis at both intermediate and late stages of HF. Moreover, analogous to murine HF, the plasma milieu in human acute decompensated HF strongly promoted neutrophil trafficking. Collectively, these results support a key tissue-injurious role for neutrophils and their associated cytotoxic products in ischemic cardiomyopathy and suggest that neutrophils are potential targets for therapeutic immunomodulation in this disease.

QRS fragmentation does not predict mortality in survivors of acute myocardial infarction.

Despite advances in coronary revascularization and in heart failure management, myocardial infarction survivors remain at substantially increased mortality risk. Precise risk assessment and risk-adapted follow-up care are crucial to improve their outcomes. Recently, the fragmented QRS complex, i.e. the presence of additional spikes within the QRS complexes on a 12-lead electrocardiogram, has been discussed as a potential non-invasive risk predictor in cardiac patients. The aim of this study was to evaluate the prognostic meaning of the fragmented QRS complex in myocardial infarction survivors. 609 patients with narrow QRS complexes <120 ms were included in a prospective cohort study while hospitalized for myocardial infarction and followed for 5 years. The prevalence of the fragmented QRS complex in these patients amounted to 46.8% (285 patients). These patients had no increased hazard of all-cause death (HR 0.84, 95%-CI 0.45-1.57, p = 0.582) with a mortality rate of 6.0% compared to 7.1% in patients without QRS fragmentations. Furthermore, the risks of cardiac death (HR 1.28, 95%-CI 0.49-3.31, p = 0.613) and of non-cardiac death (HR 0.6, 95%-CI 0.26-1.43, p = 0.25) were not significantly different in patients with QRS fragmentations. However, patients with QRS fragmentations had increased serum creatine kinase concentrations (1438U/l vs. 1160U/l, p = 0.039) and reduced left ventricular ejection fractions (52% vs. 54%, p = 0.011). The hypothesis that QRS fragmentation might be a prognostic parameter in survivors of myocardial infarction was not confirmed. But those with QRS fragmentation had larger myocardial infarctions, as measured by creatine kinase and left ventricular ejection fraction.

Integrin alpha 11 is cardioprotective post myocardial infarction, regulating infarct formation and collagen organization

Abstract Background Post Myocardial Infarction (MI), fibrosis and in particular collagen production is an important response in order to replace apoptotic cells within the injured area and stabilize the heart wall1. Cardiac fibroblasts in and around the infarct region under mechanical and biochemical stress transform into myofibroblasts, secreting collagen to help stabilize the infarct segment2. In the short term this is an appropriate response to avoid rupture and death3. However, Long term collagen deposition will increase ventricular stiffness reducing compliance leading to further cardiac dysfunction and heart failure4. Mechanical activation of collagen production and fibrosis is understood to be a significant mediator of cardiac fibrosis, yet the mechanisms controlling mechanical activation of fibrosis are not well understood5,6. Purpose Here, we sort to investigate the role of Integrin α11 in cardiac remodelling post MI, a collagen binding integrin which preferentially binds to type I collagen and, is significantly upregulated post MI4,7. Methods Fibroblast Conditional α11 knockout (KO) and Wildtype Littermates (WT) underwent either SHAM or left anterior descending aorta (LAD) ligation surgery. Cardiac function was assessed with echocardiography and pressure volume loops. Ventricle samples were processed for FFPE histological/immunohistochemical analysis with hematoxylin/eosin, Collagen I &amp; III antibodies. Finally, Second Harmonic generation microscopy was undertaken to identify collagen organisation with previously validated CurveAlign and CT-Fire algorithms. Results α11KO and WT mice demonstrated similar cardiac function. There was evidence of basal structural differences as Collagen I (P&amp;lt;0.05) and III (P&amp;lt;0.0001) deposition was reduced along with cardiac myocyte size (P&amp;lt;0.0001) in α11KO mice. In response to LAD ligation α11KO mice had significantly worse mortality (∼57% v’s ∼22%, P&amp;lt;0.05) which, correlated with an increased MI size (WT=∼39%, α11KO=∼64% P&amp;lt;0.05). Cardiac function 2 days following ligation measured by echo demonstrated that Fractional Area Change (FAC) (23%±2 v’s 16%±2 P&amp;lt;0.05) and Cardiac Output (8.5ml±1 v’s 5ml±0.7, P&amp;lt;0.05) were significantly worse in α11 KO compared to WT mice. The reduced function persisted 4 weeks post ligation as FAC was significantly worse in α11KO mice (∼9%±2%, P&amp;lt;0.0001) compared to WT (∼19%±1%). Moreover, α11KO mice that survived MI had significantly more collagen I (P&amp;lt;0.0001) content in the remote, peri-infarct and infarct zone’s than that of WT along with a lack of hypertrophic response. Finally, Collagen alignment measured using SHG images with CurveAlign demonstrated collagen fibres had significantly less structural alignment in α11KO mice (P&amp;lt;0.05). Conclusion We demonstrate a cardioprotective role for Integrin α11 post myocardial infarction. Where, the lack of α11 leads to worsened mortality, larger MI, worsened cardiac function and impaired collagen organisation in the infarct post MI.

Abstract 14730: The Effect of Electronic Cigarette Exposure With Nicotine on Expression of Inflammatory Genes and Blood Parameters in a Chronic Myocardial Infarction Model

Background: There are no data available regarding the effects of chronic electronic cigarette (eC) exposure on inflammatory gene expressions after myocardial infarction (MI) and whether eC could alter blood counts and chemistries in this setting. We determined the effect of eC on expression of genes for inflammatory cytokines and receptors and blood parameters during the healing phase of MI. Methods and Results: Sprague Dawley rats of either sex were subjected to a proximal left coronary artery occlusion to induce a large anterior wall MI. At 1 week, rats were randomized to exposure to air or E-cig with nicotine (eC Nic + ) for 12 weeks. After 12 weeks of exposure, rat inflammatory cytokine and receptor PCR array was performed (n=4 in each group). The data showed 70 out of 84 inflammatory-related genes were downregulated in the eC Nic+ group versus the air group and 11 downregulated genes reached a significant difference. Interleukin 6 (IL6), Tumor necrosis factor superfamily (TNF), Chemokine (C-C motif) ligand 12 (Ccl12), and C-X-C Motif Chemokine Receptor 3 (Cxcr3) gene expressions were significantly decreased by -6.49 fold, p=0.0048, -2.63 fold, p=0.0227, -2.71 fold, p=0.0146, and -2.28 fold, p=0.0067, respectively, in the eC Nic+ group vs air group. The rats in eC Nic+ group had significantly decreased white blood cell (WBC), lymphocyte and platelet count compared to the air group (Figure). Conclusions: Exposure to eC Nic+ alters the expression of inflammatory genes and decreases blood immune cells during the healing phase of MI. Our findings suggest that chronic inhalation of e-cigarette aerosols can suppress the immune and inflammatory response in the already compromised setting of MI.

Abstract 13361: The Effect of Electronic Cigarette Exposure on Flow Mediated Vasodilation and LV Remodeling in a Chronic Myocardial Infarction Model

Introduction: There is little information about the effect of electronic cigarette (e-C) exposure on the cardiovascular system in the setting of myocardial infarction (MI) and whether e-C’s could alter vascular or cardiac function during the healing phase of MI. We determine the effect of e-C on endothelial function, cardiac remodeling and function during the healing phase of MI. Methods: Sprague Dawley rats (both sexes) were anesthetized and subjected to a proximal left coronary artery occlusion to induce a large anterior wall MI. At one week, rats were randomized to receive either 12 weeks of exposure to purified air (n=37) or e-cig vapor plus 15 mg/ml of nicotine (e-Cn=32). At 12 weeks endothelial function was tested by assessing femoral artery diameter and blood flow following a 5- minute femoral artery occlusion and reperfusion (ultrasound and flow probe). Cardiac function was assessed by echocardiography; remodeling was also assessed by quantitative histologic analysis. Results: Baseline blood flow in the femoral artery did not differ between groups, but peak reperfusion blood flow was blunted in the e-Cn group (1.59 ± 0.15 ml/min) vs. the air group (2.11 ± 0.18 ml/min; p=0.034). Femoral artery diameter after reperfusion was narrower in the e-Cn group (0.54 ± 0.02mm) compared to the air group (0.60 ± 0.02mm; p=0.023). Postmortem left ventricular (LV) volumes were similar in the e-Cn (0.69 ± 0.04 ml) and air groups (0.73 ± 0.04 ml; p=NS); and myocardial infarct expansion index did not differ between groups (1.4 ± 0.1 in e-Cn group versus 1.3 ± 0.1 in air group; p=NS). Gross pathology LV wall thickness was greater in the e-Cn group (1.38 ± 0.12 mm) versus the air group (1.04 ± 0.10 mm) despite no increase in blood pressure at 12 weeks in the e-CN group. LV fractional shortening by echo did not differ between groups at 12 weeks (e-Cn at 29 ± 2% and air at 27 ± 1%; p=NS). Conclusion: Exposure to e-Cn during the healing phase of MI was associated with altered endothelial function with reduced femoral artery blood flow and diameter at reperfusion, but not with worsened LV dilation or worsened cardiac function. E-Cn did increase gross pathologic LV wall thickness. E-Cn exposure during the healing phase of MI has deleterious effects on the CV system but does not dilate the LV.

Second-generation extracellular matrix patch for epicardial infarct repair

Current myocardial infarction treatments focus on improving hemodynamics rather than addressing the problem of lost myocardium impairing left ventricular function. Epicardial infarct repair with a bioactive patch placed on the ischemic area is an emerging approach to promote endogenous myocardial repair. We report the use of a second-generation CorMatrix-extracellular matrix (ECM) patch as an adjunct to surgical revascularization in treating a young patient with diffuse, multivessel coronary artery disease unamenable to PCI and a large anterior myocardial infarction. The progressive myocardial scar shrinkage and increase in left ventricular ejection fraction from 10 to 51% are generally not observed with surgical revascularization therapy alone, suggesting this new patch has adjunctive potential to current revascularization therapy.

The Impact of Mitral Regurgitation on Long-Term Outcomes in Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

It is important to clarify the precise impact of mitral regurgitation (MR) on long-term outcomes in acute myocardial infarction (AMI) patients who underwent percutaneous coronary intervention (PCI). In the Coronary Revascularization Demonstrating Outcome study in Kyoto Acute Myocardial Infarction (CREDO-Kyoto AMI) Registry Wave-2, the study population consisted of 5,266 patients with AMI who underwent PCI. The clinical outcomes of all-cause death, cardiovascular death, and hospitalization for heart failure (HF) were compared according to the severity of MR. Mild and moderate/severe MR were identified in 2,112 (40%) and 531 patients (10%), respectively. Patients with greater severity of MR were more likely to be old, had more co-morbidities, and more often presented with large myocardial infarction with HF. During median follow-up duration of 5.6 (interquartile range: 4.2 to 6.6) years, as the MR severity increased from no, mild, to moderate/severe MR, the cumulative 5-year incidences of all-cause death, cardiovascular death and hospitalization for HF incrementally increased ([15.3%, 19.6%, 33.3%], [8.9%, 11.7%, 21.0%] and [5.9%, 12.4%, 23.9%], respectively, P for all<0.001). After adjusting for confounders, however, mild and moderate/severe MR were not independently associated with the higher risks for all-cause death (hazard ratio [95% confidence interval]:1.05 [0.92 to 1.19], p=0.51, and 1.10 [0.92 to 1.32], p=0.28) and cardiovascular death (1.01 [0.85 to 1.21], p=0.89, and 0.93 [0.73 to 1.18], p=0.54) as compared with no MR. Both mild and moderate/severe MR were independently associated with the higher risks for hospitalization for HF (1.73 [1.42 to 2.11], p <0.001, and 2.23 [1.73 to 2.87], p <0.001). In a large population of patients with AMI who underwent PCI, MR was not independently associated with higher long-term mortality risk but was independently associated with higher risk for hospitalization for HF.

Brown Adipose Tissue and BMP3b Decrease Injury in Cardiac Ischemia-Reperfusion.

Despite advances in treatment, myocardial infarction (MI) is a leading cause of heart failure and death worldwide, with both ischemia and reperfusion (I/R) causing cardiac injury. A previous study using a mouse model of nonreperfused MI showed activation of brown adipose tissue (BAT). Recent studies showed that molecules secreted by BAT target the heart. We investigated whether BAT attenuates cardiac injury in I/R and sought to identify potential cardioprotective proteins secreted by BAT. Myocardial I/R surgery with or without BAT transplantation was performed in wild-type (WT) mice and in mice with impaired BAT function (uncoupling protein 1 [Ucp1]-deficient mice). To identify potential cardioprotective factors produced by BAT, RNA-seq (RNA sequencing) was performed in BAT from WT and Ucp1-/- mice. Subsequently, myocardial I/R surgery with or without BAT transplantation was performed in Bmp3b (bone morphogenetic protein 3b)-deficient mice, and WT mice subjected to myocardial I/R were treated using BMP3b. Dysfunction of BAT in mice was associated with larger MI size after I/R; conversely, augmenting BAT by transplantation decreased MI size. We identified Bmp3b as a protein secreted by BAT after I/R. Compared with WT mice, Bmp3b-deficient mice developed larger MIs. Increasing functional BAT by transplanting BAT from WT mice to Bmp3b-deficient mice reduced I/R injury whereas transplanting BAT from Bmp3b-deficient mice did not. Treatment of WT mice with BMP3b before reperfusion decreased MI size. The cardioprotective effect of BMP3b was mediated through SMAD1/5/8. In humans, the plasma level of BMP3b increased after MI and was positively correlated with the extent of cardiac injury. The results of this study suggest a cardioprotective role of BAT and BMP3b, a protein secreted by BAT, in a model of I/R injury. Interventions increasing BMP3b levels or targeting Smad 1/5 may represent novel therapeutic approaches to decrease myocardial damage in I/R injury.

The effect of plasma transfusion in an experimental two-hit animal model of transfusion-associated circulatory overload with heart failure.

Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-related morbidity and mortality. TACO follows a two-hit pathophysiology, where comorbidities like cardiac or renal failure act as the first hit followed by blood transfusion as a second hit. Observational studies suggest that plasma transfusion is more likely to cause TACO than other blood products. We conducted a randomized animal study to gather evidence that plasma transfusion can induce TACO. As a first hit a large myocardial infarction was created in male Wistar rats. Then animals were randomized to receive 4 units of solvent/ detergent-treated pooled plasma (SDP), fresh frozen plasma (FFP), a colloid control (albumin 5%) or a crystalloid fluid control (Ringer's lactate) (n=10 per group). The primary outcome was the difference between pre- and post-transfusion left-ventricular end diastolic pressure (ΔLVEDP). Secondary outcomes were markers for acute lung injury; lung wet/dry weight ratio, PaO2/FiO2 ratio and pulmonary histological assessment. Pre-transfusion characteristics were similar between groups. ΔLVEDP increased significantly after transfusion with SDP (7.7 mmHg; 4.5-10.5) and albumin (13.0 mmHg; 6.5-15.2), but not after FFP (7.9 mmHg, 1.1; 11.3) compared to infusion with Ringer's lactate (0.6 mmHg; 0.4-2.2), p=0.007, p=0.0005 and p=0.14 respectively. There were no significant differences in ΔLVEDP between groups receiving SDP, FFP or albumin. There was no increase in acute lung injury in any group compared to other groups. Circulatory overload, measured as ΔLVEDP, was induced after transfusion of SDP or albumin, but not after infusion of Ringer's lactate. These results show that the effect of plasma transfusion on ΔLVEDP differs from fluid overload induced by crystalloid infusion. Colloid osmotic pressure may be an important component in the development of TACO and should be a target for future research.

Severe Left Ventricular Dysfunction Earlier after Acute Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention: Predictors and In-Hospital Outcome- A Middle Eastern Tertiary Center Experience.

A single-center retrospective study included 2863 myocardial infarction patients who were admitted to our center and treated with successful PPCI. Out of 2863 consecutive patients who underwent PPCI from May 2018 to August 2021, 1021 (36%) developed server LV dysfunction. They showed a higher history rate of ischemic heart disease and previous revascularization before AMI (P = 0.05 and 0.001 respectively). Also, they presented more with anterior myocardial infarction (P < 0.001) and heavy thrombus burden (P = 0.002 and 0.004 for indication of peri-procedural glycoprotein IIb/IIIa inhibitors use and thrombus aspiration) compared to the other group of patients. Moreover, they also had a more critical anatomy of coronary artery disease (P < 0.001 for both left main and multi-vessel coronary artery disease). The independently associated predictors for early severe LV dysfunction post-AMI treated with PPCI were anterior localization of AMI, the greater value of troponin, renal impairment, and severe coronary artery disease (P= <0.001, 0.036, 0.002, and <0.07 respectively). Despite optimal treatment for those patients, they showed poor outcomes including in-hospital morbidity and mortality (P < 0.001). Sizable proportion of patients following successful PPCI develop severe LV systolic dysfunction and associated with poor clinical outcomes. Larger myocardial infarction, renal impairment, and severe coronary artery disease are independent predictors of severe LV systolic dysfunction post-PPCI.

Mechanical complications of myocardial infarction: basic aspects of pathogenesis and approaches to surgical treatment

Ischemic heart disease is a leading cause of mortality of the adult population. The most mortality of all forms of ischemic heart disease is occurred with development of myocardial infarction. Meanwhile, the direct cause of death are complications of myocardial infarction. Since the advent of catheter-based and surgical reperfusion, there has been a significant decrease in the frequency of these complications. However, patients with large myocardial infarctions or those who do not receive necessary revascularization in time remain at risk of mechanical complications of acute myocardial infarction. The most common mechanical complications are rupture of the papillary muscles of the mitral valve and acute mitral regurgitation, interventricular septal defect, forming of aneurysms and pseudoaneurysms, and free-wall rupture. Although these complications are rare, their prognosis is unfavourable and is associated with high mortality at the prehospital and hospital stage. Early diagnosis, determination of optimal treatment tactics are crucial for increasing the survival rate of patients.

SGLT2 Inhibition in Acute Myocardial Infarction-A Comprehensive Review.

In heart failure as well as in chronic kidney disease sodium-glucose cotransporter 2 (SGLT2) inhibitors have changed the landscape of medical therapy. Originally developed for use in diabetes, an unforeseen cardiovascular benefit extended SGLT2 inhibitor use from antihyperglycemic agents to cardiovascular and renal risk modifying agents. As their benefit in cardiovascular disease is independent from the diabetic state as well as the left ventricular ejection fraction it is the only class of therapy recommended throughout the spectrum of heart failure. Until very recently, the remaining gap in evidence has been data on the safety and efficacy of SGLT2 inhibitors in patients with acute myocardial infarction (MI) as former trials of SGLT2 inhibitors to date have excluded patients with recent ischemic events. As the first out of three trials conducted in post MI SGLT2 inhibitors therapy the EMMY trial was published. EMMY randomized 476 patients shortly after percutaneous intervention for recent large MI to either 10 mg of empagliflozin daily or placebo. The primary endpoint of changes in N-terminal pro brain natriuretic peptide (NT-proBNP) over 26 weeks as well as the functional and structural secondary endpoints were met. This provides first evidence of SGLT2 inhibitors-mediated beneficial results in this group of patients. We here discuss these results in the light of the two upcoming outcome trials (DAPA-MI and EMPACT-MI) with regard to the future role of this class of drugs early after MI.

Fibrin-Enriched Cardiac Extracellular Matrix Hydrogel Promotes In Vitro Angiogenesis.

Angiogenesis is essential for cardiac repair after myocardial infarction. Promoting angiogenesis has been demonstrated as an effective approach for myocardial infarction treatment. Several different strategies for inducing myocardial angiogenesis have been explored, including exogenous delivery of angiogenic genes, proteins, microRNAs, cells, and extracellular vesicles. Various types of injectable hydrogels have been investigated for cardiac tissue repair. One of the most promising injectable hydrogels in cardiac regeneration is a cardiac extracellular matrix hydrogel that is derived from decellularized porcine myocardium. It can be delivered minimally invasively via transendocardial delivery. The safety and efficacy of cardiac extracellular matrix hydrogels have been shown in small and large animal myocardial infarction models as well as clinical trials. The main mechanisms underlying the therapeutic benefits of cardiac extracellular matrix hydrogels have been elucidated and involved in the modulation of the immune response, downregulation of pathways related to heart failure progression and fibrosis, upregulation of genes important for cardiac muscle contraction, and enhancing cardiomyocyte differentiation and maturation from stem cells. However, no potent capillary network formation induced by cardiac extracellular matrix hydrogels has been reported. In this study, we tested the feasibility of incorporating a fibrin matrix into cardiac extracellular matrix hydrogels to improve the angiogenic properties of the hydrogel. Our in vitro results demonstrate that fibrin-enriched cardiac extracellular matrix hydrogels can induce robust endothelial cell tube formation from human umbilical vein endothelial cells and promote the sprouting of human mesenchymal stem cell spheroids. The obtained information from this study is very critical toward the future in vivo evaluation of fibrin-enriched cardiac extracellular matrix hydrogels in promoting myocardial angiogenesis.

Abstract 15385: Integrin Alpha 11 is a Critical Regulator of Cardiac Remodelling, Fibrosis and Infarct Formation Following Myocardial Infarction

Cardiac fibrosis (CF), a key feature of cardiac remodelling, defined as the accumulation of excessive amounts of extracellular matrix (ECM), in response to injuries such as myocardial infarction (MI). Cardiac fibroblasts within and surrounding the injured area respond to biochemical and mechanical stimuli transforming into myofibroblasts and begin to secrete collagen. Long term collagen production reduces ventricular compliance and ultimately results in further cardiac dysfunction leading to heart failure. Mechanical activation of collagen production is understood to be a significant mediator of cardiac fibrosis. However, the mechanisms via which mechanical stimuli initiate cardiac fibroblast activation are not well understood. Therefore, we sort to investigate the role of Integrin ⍺11, a collagen binding integrin which preferentially binds to type I collagen, in response to cardiac injury. Fibroblast conditional ⍺11 knockout (KO) mice demonstrated similar cardiac function to that of Wildtype littermates (WT). However, interstitial collagen I (P&lt;0.05) and III (P&lt;0.0001) content was reduce along with cardiac myocyte size (P&lt;0.0001). In response to ligation of the left anterior descending aorta ⍺11 KO mice had significantly increased Infarct size 24 hours post MI (WT=39%, ⍺11KO=64% P&lt;0.05). Larger MI’s resulted in increased mortality in ⍺11 KO mice (22% v’s 57%, P&lt;0.05) due to rupture. Cardiac function 2 days following MI measured by echo demonstrated that Fractional Area Change (FAC) (23% ±1.812 v’s 16%±2.311, P&lt;0.05) and Cardiac Output (8.53ml±1.045 v’s 4.98ml±0.67, P&lt;0.05) were significantly worse in ⍺11 KO compared to WT mice. In the later remodelling response 4 weeks post MI, FAC was again significantly worse for ⍺11 KO mice (~9% ±1.659%, P&lt;0.0001) compared to WT (~19% ± 0.9810%). Moreover, ⍺11 KO mice that survived MI had significantly more collagen I (P&lt;0.0001) content in the remote, peri-infarct and infarct zone’s than that of WT along with, a lack of hypertrophic response. In conclusion, the loss ⍺11 results in increased ventricular dilation, impairs cardiac function and, was associated with increased mortality due to rupture following MI. In mice which survived MI ⍺11 deletion led to increased CF and blunted cardiac myocyte hypertrophy.

Abstract 10121: Hypoimmunogenic Human Induced Pluripotent Stem Cells Derived Cardiomyocytes for Cardiac Regeneration

Introduction: Post-transplant rejection resulting from human leukocyte antigen (HLA) mismatch is a challenge in allogeneic cell therapy. Human amniotic fluid stem cell-derived iPSCs (hAFSC-iPSCs) are proved to have immune privilege. Hypothesis: hAFSC-iPSC derived cardiomyocytes (hAFSC-iPSC-CMs) are less immunogenic. Methods and Results: hAFSC-iPSCs and hAFSC-iPSC-CMs expressed classical HLA-Ia (HLA-A, -B and -C) and non-classical HLA-Ib but did not have HLA-II expression, indicating that these cells may not be highly immunogenic. We did T Cell Assays to confirm low immunogenicity of hAFSC-iPSC-CMs. We did ischemia-reperfusion surgery of left anterior descending coronary artery to create large transmural myocardial infarction in rats. At post-infarct 4 days, we injected human pluripotent stem cell-derived cardiomyocytes (1.0х10 7 cells/kg), including human embryonic stem cell-derived cardiomyocytes (hESC-CMs), hiPSC-CMs and hAFSC-iPSC-CMs, into the infarcted myocardium. Using very low dose of cyclosporine A (CsA, 2.5 mg/kg/day), only hAFSC-iPSC-CMs transplantation could improve post-infarct cardiac function (left ventricular ejection fraction improvement in hAFSC-iPSC-CMs, hESC-CMs and hiPSC-CMs: 13.1 ± 1.8%, 0.6 ± 1.7% and -1.9 ± 1.6%, respectively). Compared with hESC-CMs and hiPSC-CMs, hAFSC-iPSC-CM transplantation remuscularized the infarcted myocardium with infarct size reduction. Using very low dose CsA, these engrafted hAFSC-iPSC-CMs resulted in a 3-month survival in vivo. hAFSC-iPSC-CMs expressing non-classical HLA-Ib evaded detection and attack by natural killer (NK) cells and cytotoxic T cells because these hAFSC-iPSC-CMs activated the protein tyrosine phosphatase SHP-1/SHP-2 signalling pathway of NK cells and cytotoxic T cells which downregulated signal transducer and activator of transcription 1 (STAT-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression. Conclusions: We demonstrated the immune privilege of hAFSC-iPSC-CM for cardiac regeneration. HLA-Ib-expressing hiPSCs with reduced HLA-II expression are less immunogenic and may serve as platforms for regenerative medicine.