Irreversible Myocardial Injury Research Articles

Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids.

Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating clinically relevant in vitro cell models. This study focuses on generating self-organizing heart organoids (HOs) using human-induced pluripotent stem cells (hiPSCs). These organoids consist of cardiomyocytes, fibroblasts, and endothelial cells, mimicking the cellular composition of the human heart. The multi-cellular composition of HOs was confirmed through various techniques, including immunohistochemistry, flow cytometry, q-PCR, and single-cell RNA sequencing. Subsequently, HOs were subjected to hypoxia-induced ischemia and ischemia-reperfusion (IR) injuries within controlled culture conditions. The resulting phenotypes resembled those of acute myocardial infarction (AMI), characterized by cardiac cell death, biomarker secretion, functional deficits, alterations in calcium ion handling, and changes in beating properties. Additionally, the HOs subjected to IR efficiently exhibited cardiac fibrosis, displaying collagen deposition, disrupted calcium ion handling, and electrophysiological anomalies that emulate heart disease. These findings hold significant implications for the advancement of in vivo-like 3D heart and disease modeling. These disease models present a promising alternative to animal experimentation for studying cardiac diseases, and they also serve as a platform for drug screening to identify potential therapeutic targets.

Mechanisms of Atherosclerotic Plaque Instability

Cardiovascular disease (CVD) is the leading cause of mortality in humans worldwide. The main cause of CVD is the formation of thrombi due to by unstable atherosclerotic plaque rupture on the arterial wall. Long-term accumulation of thrombi results in vascular remodeling, and subsequent-stenosis of the lumen obstructs the blood flow, thereby leading to myocardial tissue ischemia and hypoxia. Sustained ischemia and hypoxia lead to myocyte necrosis, resulting in irreversible myocardial injury. Many molecular and cellular mechanisms are associated with atherosclerotic plaque instability (API). For example, macrophages can produce various inflammatory factors, adhesion factors, chemokines and matrix metalloproteinases (MMPs), which play important roles in the pathophysiological mechanisms of API and in maintaining plaque stability. These molecules may help predict unstable atherosclerotic plaques. If the plaque is stable, it will not be prone to rupture or thrombosis. Accordingly, in this review, we will discuss the different pathophysiological mechanisms of API and the related roles of macrophages in the mechanisms of API mainly in animal models and humans. We believe this review will provide a theoretical basis for the development of treatments and diagnostic approaches for the management of API.

The role of postoperative trimetazidine therapy in on-pump coronary artery bypass surgery.

Coronary artery bypass surgery remains the gold standard in the treatment of patients with ischemic heart disease. However, the increased oxidative stress caused by the release of free radicals during the ischemia-reperfusion time is a well-known pathophysiological process during and after coronary revascularization procedures. It may lead to reversible and irreversible myocardial injury.

Irreversible myocardial injury attenuates the benefits of sacubitril/valsartan in heart failure patients

BackgroundDespite the established benefits of angiotensin receptor-neprilysin inhibitor (ARNI) in heart failure with reduced ejection fraction (HFrEF) across various etiologies, there are controversies regarding the effects of ARNI in patients with irreversible myocardial injury. The aim of this study is to investigate the impact of irreversible myocardial injury on the benefits of ARNI treatment in patients with HFrEF, consisted of both ischemic and non-ischemic etiologies. Methods and resultsWe conducted a retrospective single-center study including 409 consecutive patients with HFrEF treated with ARNI between March 2017 and May 2020. Irreversible myocardial injury was defined as nonviable myocardium without contractile reserve, which suggests a limited potential for recovery of left ventricular function and geometry. At baseline, irreversible myocardial injury was observed in 129 (31.5%) patients. Composite outcome was cardiovascular death or hospitalization for heart failure, which occurred in 56 (43.4%) and 61 (21.8%) patients with and without irreversible myocardial injury, respectively. On multivariable analysis, irreversible injury presence, but not ischemic etiology, was an independent predictor of composite outcome (hazard ratio 2.16, 95% confidence interval 1.33–3.49). Mediation analysis revealed that the increased risk of the composite outcome due to irreversible myocardial injury was mediated by attenuated LV reverse remodeling (Z value = 2.02, P = 0.043). ConclusionsThe presence of irreversible myocardial injury was significantly associated with the response to ARNI treatment in patients with HFrEF, regardless of etiology.

The association between marathon running and high-sensitivity cardiac troponin: A systematic review and meta-analysis.

Marathon running is an extreme sport with a distance of about 42 kilometers. Its relationship to high-sensitivity cardiac troponin (hs-cTn) remains controversial. As the gold standard for detecting myocardial injury, the trends of hs-cTn before and after a marathon were investigated and analyzed. A literature search was conducted in PubMed, EMBASE, and Cochrane Library databases by combing the keywords marathon and troponin, and studies regarding high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) concentrations before and after marathon running (not for half-marathon and ultra-marathon) were included. "Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group" were used to assess the risk of bias. Statistical analysis was performed using Review Manager, presenting data as mean values and 95% confidence intervals (CIs). Sensitivity analysis and subgroup analysis were performed if there was high heterogeneity among studies based on I2 statistic. A total of 13 studies involving 824 marathoners were included in this systematic review and meta-analysis. Both hs-cTnI (MD 68.79 ng/L, [95% CI 53.22, 84.37], p< 0.001) and hs-cTnT (MD 42.91 ng/L, [95% CI 30.39, 55.43], p< 0.001) were elevated after running a marathon, but the concentration of hs-cTnT returned to baseline after 72 to 96 h post-race (MD 0.11ng/L, [95% CI -1.30, 1.52], p= 0.88). The results of subgroup analysis demonstrated that the 99th percentile upper reference limit of hs-cTnT might be the source of heterogeneity. The concentrations of hs-cTnI and hs-cTnT were increased after marathon running, but the change of hs-cTnT is usually not seen as irreversible myocardial injury.

Inhibition of Pyruvate kinase M2 (PKM2) by shikonin attenuates isoproterenol-induced acute myocardial infarction via reduction in inflammation, hypoxia, apoptosis, and fibrosis.

Myocardial infarction (MI) is a major cause of mortality and disability globally. MI results from acute or chronic myocardial ischemia characterized by an imbalance of oxygen demand and supply, leading to irreversible myocardial injury. Despite several significant efforts in the understanding of MI, the therapy of MI is not satisfactory due to its complicated pathophysiology. Recently, therapeutic potential of targeting pyruvate kinase M2 (PKM2) has been postulated in several cardiovascular diseases. PKM2 gene knockout and expression studies implicated the role of PKM2 in MI. However, the effects of pharmacological interventions targeting PKM2 have not been investigated in MI. Therefore, in the present study, effect of PKM2 inhibitor has been investigated in the MI along with elucidation of possible mechanism(s).MI in rats was induced by administrations of isoproterenol (ISO) at a dose of 100mg/kg s.c. for two consecutives days at 24-h interval. At the same time, shikonin (PKM2 inhibitor) was administered at 2 and 4mg/kg in ISO-induced MI rats. After the shikonin treatment, the ventricular functions were measured using a PV-loop system. Plasma MI injury markers, cardiac histology, and immunoblotting were performed to elucidate the molecular mechanism.Treatment of shikonin 2 and 4mg/kg ameliorated cardiac injury, reduced infarct size, biochemical alterations, ventricular dysfunction, and cardiac fibrosis in ISO-induced MI. Expression of PKM2 in the ventricle was reduced while PKM1 expression increased in the shikonin treated group, indicating PKM2 inhibition restores PKM1 expression. In addition, PKM splicing protein (hnRNPA2B1 & PTBP1), HIF-1α, and caspase-3 expression were reduced after shikonin treatment.Our findings suggest that pharmacological inhibition of PKM2 with shikonin could be a potential therapeutic strategy to treat MI.

Cyclocreatine Phosphate: A Novel Bioenergetic/Anti-Inflammatory Drug That Resuscitates Poorly Functioning Hearts and Protects against Development of Heart Failure

Irreversible myocardial injury causes the exhaustion of cellular adenosine triphosphate (ATP) contributing to heart failure (HF). Cyclocreatine phosphate (CCrP) was shown to preserve myocardial ATP during ischemia and maintain cardiac function in various animal models of ischemia/reperfusion. We tested whether CCrP administered prophylactically/therapeutically prevents HF secondary to ischemic injury in an isoproterenol (ISO) rat model. Thirty-nine rats were allocated into five groups: control/saline, control/CCrP, ISO/saline (85 and 170 mg/kg/day s.c. for 2 consecutive days), and ISO/CCrP (0.8 g/kg/day i.p.) either administrated 24 h or 1 h before ISO administration (prophylactic regimen) or 1 h after the last ISO injection (therapeutic regimen) and then daily for 2 weeks. CCrP protected against ISO-induced CK-MB elevation and ECG/ST changes when administered prophylactically or therapeutically. CCrP administered prophylactically decreased heart weight, hs-TnI, TNF-α, TGF-β, and caspase-3, as well as increased EF%, eNOS, and connexin-43, and maintained physical activity. Histology indicated a marked decrease in cardiac remodeling (fibrin and collagen deposition) in the ISO/CCrP rats. Similarly, therapeutically administered CCrP showed normal EF% and physical activity, as well as normal serum levels of hs-TnI and BNP. In conclusion, the bioenergetic/anti-inflammatory CCrP is a promising safe drug against myocardial ischemic sequelae, including HF, promoting its clinical application to salvage poorly functioning hearts.

Changes in myocardial work associated with pediatric kidney transplantation: A pilot study of short-term postoperative effect.

The study was mainly to evaluate the changes of left ventricular (LV) myocardial work (MW) in children with CKD stage 5 within 3 months after kidney transplantation (KTx). Forty-three successful KTx recipients (mean age 10.6 years, 58% male) in childhood and 28 healthy children were enrolled. General clinical characteristics and laboratory parameters were collected. Cardiac structure, function, and LV MW were assessed by echocardiography before and after KTx. The results showed that significantly improvement was observed in LV global MW index (GWI), constructive MW (GCW), and wasted MW (GWW) (p<.01), but not in MW efficiency (GWE) and global longitudinal strain (GLS) (p>.05). Besides, blood pressure (BP), renalgraftfunction, LV ejection fraction (LVEF), and LV mass index (LVMi) had obviously improved after KTx (p<.05). Nevertheless, compared with healthy children, higher BP, LVMi, GWW, more deteriorated LV diastolic function and lower GWE were still observed in patients after KTx. The ratio of dialysis duration to CKD course were negatively correlated with the improvements of GWE (p=.004), GWI (p=.01), and GCW (p=.01). In conclusion, a portion of LV MW parameters were obviously improved in children received KTx. Thus, LV MW was superior to GLS in evaluating LV systolic function recovery in these patients. Those patients with insignificant MW improvement should be closely monitored, and adjusted the treatment strategies timely to avoid serious and irreversible myocardial injury after KTx.

Pulsed-field ablation: Computational modeling of electric fields for lesion depth analysis.

BackgroundPulsed-field ablation (PFA) is an emerging and promising nonthermal technology for cardiac ablation. The effective applied voltage to achieve adequate irreversible myocardial injury is not well studied. The pulsed-field strength remains independent of tissue contact; therefore, PFA is assumed to be an ablation technology, not mandating the need for tissue contact.ObjectiveDetermine the effect of applied voltage and distance to surface on depth of myocardial injury using PFA.MethodsA computational model was developed and validated based on extracted data from in vivo studies to examine the effect of different applied voltages and the impact of distance between the catheter and endocardial surface on the depth of irreversible myocardial injury using PFA.ResultsThe depth of lesions created by PFA are dose-dependent, and there is a direct correlation between applied PFA voltages and depth of irreversible myocardial injury. The minimum applied voltage of PFA required to create a lesion deeper than 1 mm is 300 volts. The catheter-tissue contact plays a pivotal role in determining lesion depth. With optimal catheter contact in the absence of trabeculation, the minimal applied energy required to achieve a 3-mm-deep lesion is 700 volts. A minor increase in the catheter-tissue distance of 1–2 mm doubles the minimum required applied voltage, increasing it to 1500 volts.ConclusionPFA is an important new technology that is proposed to be more efficacious and safer than currently used thermal ablation. Here we demonstrate the impact of dose dependence and the need for maintaining tissue contact during ablation.

The value of perioperative biomarker release for the assessment of myocardial injury or infarction in cardiac surgery

Abstract OBJECTIVES Cardiac biomarkers are indicators of irreversible cell damage. Current myocardial infarction (MI) definitions require concomitant clinical characteristics. For perioperative MI, a correlation of biomarker elevations and mortality has been suggested. Definitions emerged relying on cardiac biomarker release only. This approach is questionable as several clinical and experimental scenarios exist where relevant biomarker release can occur apart from MI. METHODS We reviewed the clinical and basic science literature and revealed important aspects regarding the use and interpretation of cardiac biomarker release with special focus on their interpretation in the perioperative setting. RESULTS Ischaemic biomarkers may be released without cell death in multiple conditions, such as after endurance runs in athletes, temporary inotropic stimulation in animal models and flow variations in in vitro cell models. In addition, access through atrial tissue during cannulation or concomitant valve procedures adds sources of enzyme release that may not be related to ventricular ischaemia (i.e. MI). Such non-cell death-related mechanisms may explain the lack of poor correlations of enzyme release and long-term outcomes in recent trials. In addition, the 3 main biomarkers, troponin T, I and creatine kinase myocardial band, differ in their release kinetics, which may differentially trigger MI events in trial patients. CONCLUSIONS The identification of irreversible myocardial injury in cardiac surgery based only on biomarker release is unreliable. Cell death- and non-cell death-related mechanisms create a mix in the perioperative setting that requires additional markers for proper identification of MI. In addition, the 3 most common ischaemic biomarkers display different release kinetics adding to the confusion. We review the topic.

Perturbations in cardiac metabolism in a human model of acute myocardial ischaemia

IntroductionAcute myocardial ischaemia and the transition from reversible to irreversible myocardial injury are associated with abnormal metabolic patterns. Advances in metabolomics have extended our capabilities to define these metabolic perturbations on a metabolome-wide scale.ObjectivesThis study was designed to identify cardiac metabolic changes in serum during the first 5 min following early myocardial ischaemia in humans, applying an untargeted metabolomics approach.MethodsPeripheral venous samples were collected from 46 patients in a discovery study (DS) and a validation study (VS) (25 for DS, 21 for VS). Coronary sinus venous samples were collected from 7 patients (4 for DS, 3 for VS). Acute myocardial ischaemia was induced by transient coronary occlusion during percutaneous coronary intervention (PCI). Plasma samples were collected at baseline (prior to PCI) and at 1 and 5 min post-coronary occlusion. Samples were analyzed by Ultra Performance Liquid Chromatography-Mass Spectrometry in an untargeted metabolomics approach.ResultsThe study observed changes in the circulating levels of metabolites at 1 and 5 min following transient coronary ischaemia. Both DS and VS identified 54 and 55 metabolites as significant (P < 0.05) when compared to baseline levels, respectively. Fatty acid beta-oxidation and anaerobic respiration, lysoglycerophospholipids, arachidonic acid, docosahexaenoic acid, tryptophan metabolism and sphingosine-1-phosphate were identified as mechanistically important.ConclusionUsing an untargeted metabolomics approach, the study identified important cardiac metabolic changes in peripheral and coronary sinus plasma, in a human model of controlled acute myocardial ischaemia. Distinct classes of metabolites were shown to be involved in the rapid cardiac response to ischemia and provide insights into diagnostic and interventional targets.

Increased nitric oxide availability worsens the cardiac performance during early re-perfusion period in adult rats.

Re-perfusion is the standard therapy for acute myocardial infarction, despite the associated pathologies that may contribute to irreversible myocardial injury. The present study aims to clarify the alterations in cardiac activities in response to experimental cardiac ischemic arrest followed by re-perfusion in isolated hearts perfused with nitric oxide (NO) donor, l-arginine, or NO inhibitor, Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME), to shed light on the possible role of NO in the re-perfusion process. Hearts isolated from adult Wistar rats were studied on Langendorff preparation under basal conditions and during 30min re-perfusion following 30min of total global ischemia. Rats were randomly divided into three groups; control and l-arginine or l-NAME infused heart groups. Cardiac tissue content of malondialdhyde, catalase and nitrite was also measured. Compared to the control group, both l-arginine and l-NAME infused hearts showed increased basal chronotropy and myocardial flow rate. Following ischemia and during the whole period of re-perfusion, the three groups demonstrated significant deterioration in the inotropic activity and compromised myocardial flow rate. l-arginine infused hearts revealed depressed inotropy and chronotropy, weak systolic and diastolic functions with compromised myocardial flow at early 5min of re-perfusion, yet with significantly higher myocardial flow rate by the end of re-perfusion. Reducing NO availability by l-NAME revealed mild impact on the ischemia re-perfusion induced contractile dysfunction, whereas excess NO worsens cardiac performance at the early re-perfusion period.

Predictive Value of Apoptotic Factor M30 for Negative Left Ventricular Remodeling in Patients Undergoing Primary Percutaneous Coronary Intervention

Background: Left Ventricular Negative Remodeling (LVNR) following Primary Percutaneous Coronary Intervention (PPCI) is an important cause of LV systolic dysfunction due to Irreversible Myocardial Injury (IMI). Both necrosis and apoptosis contribute to IMI and LVNR. We assessed the role of specific apoptotic marker M30 in predicting LVNR in patients of anterior wall ST Elevation Myocardial Infarction (STEMI) undergoing PPCI within 12 hours of symptom onset. Methods: This prospective study was done on 100 consecutive patients of anterior wall STEMI (87 men and 13 women, mean age 52.15±12.08 years) meeting our inclusion and exclusion criteria. Blood sample for M30 was drawn at 24 hours after symptom onset, when it reaches peak level. Transthoracic echo was done in each patient at 24 hours after PPCI and at 6 months. LVNR was defined as ≥20% increase in LV end diastolic volume at 6 months after PPCI. Results: 44 patients (44%) developed LVNR at 6 months post PPCI. Diabetes mellitus (p=0.032), symptom onset to balloon time (p=0.059), CPK-MB (p=0.007) and M30 level (p=0.012) were independent predictors of LVNR. The cutoff value of M30 for predicting LVNR was 81.18u/ml with positive predictive value of 70.4% (AUC 85.3, p&lt;0.001). Conclusion: In patients of anterior wall STEMI undergoing PPCI, the apoptotic marker M30 is useful for early prediction of LVNR. This can assist in better risk stratification of patients after successful PPCI and identify the subgroup of patients who require more intensive medical follow up with antiremodeling drugs to attenuate the development of LVNR.

Abstract 13311: Cyclocreatine Phosphate: A Novel Mechanism for Preventing Development of Heart Failure

Introduction: Demand ischemia causes irreversible myocardial injury (MI) through exhaustion of cellular adenosine triphosphate (ATP). We demonstrated that enhancing myocardial ATP stores during ischemia using Cyclocreatine Phosphate (CCrP), prevents myocardial injury and maintains cardiac contractility in a variety of models. The FDA has granted CCrP Orphan Drug Status with the designation of “ Prevention of Ischemic Injury to Enhance Cardiac Graft Recovery and Survival in Heart Transplantation ” . Hypothesis: CCrP administration will prevent ischemic injury and the subsequent development of heart failure in standard isoproterenol (ISO) rat model. Methods: 20 male Wistar rats (180-220 g) were used: ISO/saline (n=6), ISO/CCrP 0.8 gm/kg/day (n=5), control/saline (n=5), control/CCrP 0.8 gm/kg/day (n=4). Rats were injected S.C. with ISO for two consecutive days at doses of 85 and 170 mg/kg/day, respectively, then left for 2 weeks. CCrP and saline were injected IP (1 ml) 24 hours and 1 hour before ISO administration, then daily for 2 weeks. Serum CK-MB (U/L) measured 24 hours after last ISO injection. After 14 days, ECHO analysis for Ejection Fraction (EF%) was conducted, as well as heart weight (mg), fibrosis and deposition of collagen. Mean ± S.E.M and one-way ANOVA analysis were used. Results: Table I shows evidence of MI after 24 hours by high elevation of CK-MB in ISO rats, while significant protection was seen in ISO/CCrP rats. After 14 days, ISO/CCrP rats showed normal EF% and heart weight, while ISO/saline rats showed significant drop in EF% and an increase in heart weight. Blinded pathology indicated marked increase of fibrin and collagen deposition in ISO/saline rats, which were not seen in ISO/CCrP rats. Healthy rats treated with CCrP for 14 days, showed no toxicity in liver and renal function. Conclusions: The bioenergetic Cyclocreatine Phosphate is a promising first-in-class cardio-protective drug that prevents the development of heart failure due to ischemia.

High-sensitivity methods for cardiac troponins: The mission is not over yet.

The measurement of cardiac troponin (cTn) is recommended by all guidelines as the gold standard for the differential diagnosis of Acute Coronary Syndromes. The aim of this review is to discuss in details some key issues regarding both analytical and clinical characteristics of the high-sensitivity methods for cTn (hs-cTn), which are still considered controversial or unresolved. In particular, the major clinical concern regarding hs-cTn methods is the difficulty to differentiate the pathophysiological mechanism responsible for biomarker release from cardiomyocytes after reversible or irreversible injury, respectively. Indeed, recent experimental and clinical studies have demonstrated that different circulating forms of cTnI and cTnT can be respectively measured in plasma samples of patients with reversible or irreversible myocardial injury. Accordingly, a new generation of hs-Tn methods should be set up, based on immunometric immunoassays or chromatographic techniques, specific for circulating peptide forms more characteristics for reversible or irreversible myocardial injury. It is conceivable that this new generation of hs-cTn methods will complete the mission regarding the laboratory tests for specific cardiac biomarkers, started more than 20 years ago, which has already revolutionized the diagnosis, prognosis and management of patients with cardiac diseases.

A RARE CASE OF FULMINANT MYOCARDITIS CAUSED BY MYCOPLASMA PNEUMONIAE SUCCESSFULLY TREATED WITH IVIG

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Fulminant myocarditis (FM) is a clinical condition which main characteristic is a rapidly progressive clinical course associated with hemodynamic compromise and high mortality risk.It is associated with an infectious process but rarely reported alongside Mycoplasma pneumoniae infection.It is unclear if the primary problem is ongoing damage from a virus, post-infectious inflammatory reactions, or both. Therefore,immunosuppressive therapy such as IVIG could be of potential benefit for treating FM.We report a rare case of FM caused by M.pneumoniae in a 27 y/o F showing improvement with IVIG therapy. CASE PRESENTATION: 27 y/o F with DM1 presented to ED with lethargy,hypotension,and tachycardia.Labwork showed DKA.She was intubated, transferred to the ICU and then started on insulin drip.On day 2, the she developed ST segment elevations,along with elevated troponin(11.86 ug/L).Echocardiogram showed EF of 42% along diffuse hypokinesis. Cardiac angiogram revealed nonobstructive CAD.On day 3, DKA resolved and patient was transitioned off insulin drip. Echocardiogram revealed worsened EF of 10-15%.Her workup showed positive M. pneumoniae IgM serology and doxycycline therapy was started, however she developed hemodynamic instability and was started on IVIG therapy.On day 4,she was weaned off vasopressor support and extubated.Repeat echocardiogram revealed EF>50% without wall motion abnormalities.Patient completed 2 days of IVIG therapy and was discharged after 8 days of hospitalization. DISCUSSION: Despite FM’s rareness, up to 12% of cases of sudden death in patients aged <40 years exhibit myocarditis.Our patient was admitted to the ICU with severe DKA, and within 24 hours she developed FM with positive M. pneumoniae IgM serology. M. pneumoniae is among the most common bacterial causes of respiratory tract infections and also associated with carditis. Myocarditis should be suspected in patients with or without cardiac signs and symptoms who present a rise in cardiac biomarker levels; changes in ECG or abnormalities of ventricular systolic function. Definitive diagnosis of myocarditis is achieved via endomyocardial biopsy(EMB).Yet, 2013 ACCF/AHA guidelines suggest excluding other causes of HF as EMB might be helpful when the results influence the management.Therefore,our patient underwent heart catheterization to rule out obstructive CAD upon the documented STEMI findings.IVIG therapy was started when she worsened hemodynamically.Yet, the use of IVIG for acute myocarditis should not be part of routine practice as its use is obscured by poor quality evidence making its use for infectious myocarditis debatable. CONCLUSIONS: The response to IVIG therapy suggests that the rapid decline of this case of infectious FM may be caused in part by an autoimmune process.Immunosuppressive treatment with IVIG in FM associated to M.pneumoniae may reduce the mortality rate and prevent irreversible myocardial injury. Reference #1: Veronese, G. (2018). Fulminant myocarditis: Characteristics, treatment, and outcomes. The Anatolian Journal Of Cardiology. https://doi.org/10.14744/anatoljcardiol.2017.8170 Reference #2: Tretjak, M., Verovnik, F., Vujkovac, B., Slemenik-Pusnik, C., & Noc, M. (2003). Severe Diabetic Ketoacidosis Associated With Acute Myocardial Necrosis. Diabetes Care, 26(10), 2959-2960. https://doi.org/10.2337/diacare.26.10.2959 Reference #3: Gupta, A., Ghimire, G., & Hage, F. (2013). Guidelines in review: 2013 ACCF/AHA Guideline for the Management of HF. Journal Of Nuclear Cardiology, 21(2), 397-399. https://doi.org/10.1007/s12350-013-9832-x DISCLOSURES: No relevant relationships by Sabree Abedrabo, source=Web Response No relevant relationships by Violeta Alvarez-Retamales, source=Web Response No relevant relationships by Mukul Bhattarai, source=Web Response No relevant relationships by Phyo Kyaw, source=Web Response No relevant relationships by Odalys Lara-Garcia, source=Web Response No relevant relationships by Suhayb Ranjha, source=Web Response No relevant relationships by Mingchen Song, source=Web Response

The study of border zone formation in ischemic heart using electro-chemical coupled computational model.

Myocardial infarction (MI) is the most common cause of a heart failure, which occurs due to myocardial ischemia leading to left ventricular (LV) remodeling. LV remodeling particularly occurs at the ischemic area and the region surrounds it, known as the border zone. The role of the border zone in initiating LV remodeling process urges the investigation on the correlation between early border zone changes and remodeling outcome. Thus, this study aims to simulate a preliminary conceptual work of the border zone formation and evolution during onset of MI and its effect towards early LV remodeling processes by incorporating the oxygen concentration effect on the electrophysiology of an idealized three-dimensional LV through electro-chemical coupled mathematical model. The simulation result shows that the region of border zone, represented by the distribution of electrical conductivities, keeps expanding over time. Based on this result, the border zone is also proposed to consist of three sub-regions, namely mildly, moderately, and seriously impaired conductivity regions, which each region categorized depending on its electrical conductivities. This division could be used as a biomarker for classification of reversible and irreversible myocardial injury and will help to identify the different risks for the survival of patient. Larger ischemic size and complete occlusion of the coronary artery can be associated with an increased risk of developing irreversible injury, in particular if the reperfusion treatment is delayed. Increased irreversible injury area can be related with cardiovascular events and will further deteriorate the LV function over time.

Myocardial extracellular volume fraction radiomics analysis for differentiation of reversible versus irreversible myocardial damage and prediction of left ventricular adverse remodeling after ST-elevation myocardial infarction.

Our study sought to explore the prognostic value of radiomic TA (texture analysis) on quantitative ECV (extracellular volume) fraction mapping to differentiate between reversible and irreversible myocardial damage and to predict left ventricular adverse remodeling in patients with reperfused STEMI (ST-elevation myocardial infarction). This observational prospective cohort study identified 70 patients (62 ± 9years, 62 men [85.70%]) with STEMI for TA who consecutively performed native and contrast T1 mapping. Texture features were extracted from each stack of ECV mapping based on ROI (region of interest) analysis. After texture feature selection and dimension reduction, five selected texture features were found to be statistically significant for differentiating the extent of myocardial injury. ROC (receiver operating characteristic) curve analysis for the differentiation of unsalvageable infarction and salvageable myocardium demonstrated a significantly higher AUC (area under the curve) (0.91 [95% CI, 0.86-0.96], p < 0.0001) for horizontal fraction than other texture features (p < 0.05). LVAR (left ventricular adverse remodeling) was predicted by those selected features. The differences in qualitative and quantitative baseline parameters and horizontal fractions were significant between the patients with and without LVAR. LGE (late gadolinium enhancement) and horizontal fraction features of infarcted myocardium in acute STEMI were the only two parameters selected in forming the optimal overall multivariable model for LVAR at 6months. Radiomic analysis of ECV could discriminate reversible from irreversible myocardial injury after STEMI. LGE as well as radiomics TA (texture analysis) of ECV may provide an alternative to predict LVAR and functional recovery. • ECV quantification was able to differentiate between infarcted myocardium and non-infarcted myocardium. • Radiomics analysis of ECV could discriminate reversible from irreversible myocardial injury. • Radiomics TA analysis shows a promising similarity with LGE findings which could aid the prognosis of myocardial infarction patients.

A REVIEW ON MANAGEMENT PRINCIPLES AND MEDICATION OF MYOCARDIAL INFARCTION

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

Myocardial Extracellular Volume Fraction Allows Differentiation of Reversible Versus Irreversible Myocardial Damage and Prediction of Adverse Left Ventricular Remodeling of ST‐Elevation Myocardial Infarction

The relationship between dynamic changes of myocardial injury in ST-elevation myocardial infarction (STEMI) patients and long-term prognosis is still unclear. To evaluate the extracellular volume fraction (ECV) in the differentiation of reversible from irreversible myocardial injury and the prediction value of left ventricular adverse remodeling in patients with STEMI after reperfusion. Prospective. Twenty-four STEMI patients after reperfusion were included FIELD STRENGTH/SEQUENCE: 3.0 T, T1 mapping, ECV, T2 -STIR, and late gadolinium enhancement (LGE). All the patients underwent cardiac MRI at four timepoints (days 1, 3, and 7, and at 6 months). The regions of interest (ROIs) were selected at the infarcted myocardium (with/without intramyocardial hemorrhage [IMH] and microvascular obstruction [MVO]). One-way analysis of variance and the Kruskal-Wallis test were used for the statistical analysis. Native T1 of MI (without MVO/IMH) gradually decreased after reperfusion (P < 0.05). The ECV of MI increased during the first 3 days and then slowly declined. Native T1 of MI with MVO/IMH was the lowest (1184 msec; 1108.5-1266), while ECV (78%; 65.5-87%) was the highest, P < 0.001. Native T1 and ECV of salvageable myocardium were higher than those of the remote myocardium but lower than those of the MI without MVO or IMH (P < 0.001). ROC analysis revealed an area under the curve (AUC) of ECV (0.85, P < 0.001) for differentiating infarcted and salvageable myocardium was higher than that of native T1 mapping (AUC: 0.63, P < 0.001) in the first week after STEMI (P < 0.0001). T1 and ECV differed significantly between patients with and without left ventricle adverse remodeling (P < 0.05). Dynamic temporal changes in reversibly and irreversibly damaged myocardia were differentiated via native T1 and ECV mapping after primary percutaneous coronary intervention in STEMI patients. ECV may better reflect microvascular injury severity and myocardial viability. MI with higher native T1 and ECV or with severe microvascular injury (MVO and IMH) was correlated with adverse LV remodeling. 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020. J. Magn. Reson. Imaging 2020;52:476-487.