Subacute Myocardial Infarction Research Articles

Widely distributable and retainable in-situ gelling material for treating myocardial infarction

Intramyocardial hydrogel injection is a promising therapy to prevent negative remodeling following myocardial infarction (MI). In this study, we report a mechanism for in-situ gel formation without external stimulation, resulting in an injectable and tissue-retainable hydrogel for MI treatment, and investigate its therapeutic outcomes. A liquid-like polymeric solution comprising poly(3-acrylamidophenylboronic acid-co-acrylamide) (BAAm), polyvinyl alcohol (PVA), and sorbitol (S) increases the viscous modulus by reducing the pre-added sorbitol concentration is developed. This solution achieves a sol-gel transition in-vitro in heart tissue by spontaneously diffusing the sorbitol. After intramyocardial injection, the BAAm/PVA/S with lower initial viscous modulus widely spreads in the myocardium and gelate compared to a viscoelastic alginate (ALG) hydrogel and is retained longer than the BAAm/S solution. Serial echocardiogram analyses prove that injecting the BAAm/PVA/S into the hearts of subacute MI rats significantly increases the fraction shortening and ejection shortening and attenuates the expansion of systolic LV diameter for up to 21 d after injection compared to the saline injection as a control, but the ALG injection does not. In addition, histological evaluation shows that only the BAAm/PVA/S decreases the infarct size and increases the wall thickness 21 d after injection. The BAAm/PVA/S intramyocardial injection is better at restraining systolic ventricular dilatation and cardiac failure in the rat MI model than in the control groups. Our findings highlight an effective injectable hydrogel therapy for MI by optimizing injectability-dependent distribution and retention of injected material. Statement of significanceIn-situ gelling material is a promising strategy for intramyocardial hydrogel injection therapy for myocardial infarction (MI). Since the sol-gel transition of reported materials is driven by external stimulation such as temperature, pH, or ultraviolet, their application in vivo remains challenging. In this study, we first reported a synthetic in-situ gelling material (BAAm/PVA/S) whose gelation is stimulated by spontaneously reducing pre-added sorbitol after contacting the heart tissue. The BAAm/PVA/S solution spreads evenly, and is retained for at least 21 d in the heart tissue. Our study demonstrated that intramyocardial injection of the BAAm/PVA/S with more extensive distribution and longer retention had better effects on preventing LV dilation and improving cardiac function after MI than that of viscoelastic ALG and saline solution. We expect that these findings provide fundamental information for the optimum design of injectable biomaterials for treating MI.

Quiescent-yet-excitable pluripotent stem cell-derived cardiomyocytes engraft without fatal arrhythmias in minipig and primates

Abstract Background Pluripotent stem cell-derived cardiomyocyte (PSC-CM) transplantation is a promising therapy for subacute myocardial infarction (MI), but transient engraftment-related arrhythmia (EA) is major barrier to clinical development (1, 2). We hypothesize that PSC-CM genetically edited to remove automaticity but otherwise functionally intact will engraft in vivo with greater arrhythmic safety. Methods Combinatorial CRISPR/Cas9 genome editing to screen for electrically quiescent PSC-CM yielded a line deficient in the depolarization-associated genes HCN4, CACNA1H, and SLC8A1, combined with overexpression of the hyperpolarization-associated gene KCNJ2. Initially, we transplanted 150 million (n=3) and 500 million gene-edited (n=2) and 150 million wildtype (n=7) PSC-CMs into a minipig model of EA, and we monitored the animals for up to seven weeks on continuous ECG for arrythmia without anti-arrhythmic therapy. In a second study, we transplanted 750 million gene-edited (n=2) and wildtype (n=1) PSC-CMs into sub-acutely infarcted Macaca nemestrina primates. Sham transplant (n=1) was also performed, and all animals were observed for up to three months with immunosuppression and beta-blocker/amiodarone therapy. Results Gene-edited PSC-CM successfully engrafted and structurally coupled with the host myocardium of minipigs (Figure 1) and nonhuman primates (Figure 2). No significant EA occurred after transplanting edited PSC-CM at the 150 million dose, whereas brief EA (<24 hours) was observed and well tolerated at the higher 500 million dose. All five minipigs survived to prespecified timepoints without complication. Conversely, wildtype PSC-CM controls demonstrated uncontrolled and fatal ventricular tachycardia (VT). Of the seven WT control minipigs, only four survived (43% mortality); three expired or were euthanized due to unstable VT or ventricular fibrillation. Arrythmia burden for both 150 and 500 million doses were significantly reduced compared to the 150 million wildtype dose in the first 30-days post-transplant (p<0.0001 for both). We then tested edited PSC-CM in a clinically relevant nonhuman primate model of sub-acute myocardial infarction using standard medical therapy including modest antiarrhythmic therapy. No arrythmia was noted in both nonhuman primates dosed with 750 million edited PSC-CM whereas significant arrhythmia was observed with wildtype despite beta blocker and amiodarone therapy. All pig and primate grafts were structurally coupled with host myocardium. Conclusion Genetically-edited PSC-CM without pacemaker-like activity significantly reduced arrythmia burden and prevented arrhythmic death in a dose-escalation study in minipig. No arrhythmia was observed in a clinically relevant nonhuman primate model of cardiac remuscularization for sub-acute myocardial infarction. This study supports continued investigation of this novel strategy to improve safety and tolerability of PSC-CM transplantation.Edited PSC-CM transplant in minipigEdited PSC-CM transplant in primates

Abstract 15057: miR-132 Inhibitor CDR 132L Attenuates Cardiac Remodeling by Exhibiting Anti-Fibrotic Effects

Introduction: Increased cardiac expression levels of miRNA miR-132 have been associated with pathological cardiac remodeling including cardiac fibrosis. As a selective inhibitor for miR-132, the synthetic antisense oligonucleotide CDR132L, is capable to reverse cellular pathology and restore normal heart function. Pharmacological inhibition of miR-132 as well as genetic knockout has been shown to protect mice from transverse aortic constriction induced cardiac remodeling including interstitial fibrosis. Methods and Results: Treatment effects of CDR132L were investigated in several different pig models of ischemic and non-ischemic heart failure (HF) with the aim to further elucidate CDR132L’s mode of action and confirm species-independent effects on fibrotic remodeling. In a pig model of subacute post myocardial infarction (MI) induced HF, CDR132L was administered on day 3 and day 28 by intravenous (IV) or intracoronary (IC) infusion at doses of 1, 5 and 10 mg/kg and followed until day 56. In a chronic post-MI HF large animal model, beneficial effects were confirmed in a 6-month study comparing 5 monthly and 3 monthly repeated IV administrations of 5 mg/kg CDR132L starting one month post-MI. Further, CDR132L was tested in a porcine model of percutaneous aortic constriction by implantation of a reduction stent in the thoracic aorta and two IC injections of CDR132L on day 0 and day 28 followed for 56 days. As part of the pharmacodynamic analyses in these models, paraffin sections of cardiac tissue from the left ventricular remote region were stained with picrosirius red (PSR) and fibrosis was assessed based on collagen quantity. Analysis of fibrosis in PSR-staining revealed that the degree of interstitial fibrosis was significantly reduced in CDR132L treatment groups compared to placebo between 22% and 61%. Moreover, results of the first-in-human safety and tolerability study of CDR132L in patients with stable HF of ischemic origin (NCT04045405) showed encouraging positive trends for relevant cardiac fibrosis biomarkers. Conclusion: By blocking aberrant miR-132 expression, CDR132L is capable to halt and reverse pathological cardiac remodeling partly due to its anti-fibrotic effects.

Totally endoscopic trans-mitral removal of a left ventricular apical thrombus through right thoracotomy in a patient with subacute anterior myocardial infarction: a case report

BackgroundLeft ventricular thrombosis confers a life-threatening risk of systemic embolism; therefore, it requires prompt intervention. Although anticoagulation is the primary treatment, surgery is indicated in instances of large or/and mobile thrombus or when there is potential for recovery of ventricular contraction. However, standard left ventriculoplasty with thrombectomy carries risks of cardiac dysfunction due to left ventriculotomy.Case presentationA 70-year-old man developed chest pain and vomiting 3 weeks before presenting to our hospital. A chest radiograph showed substantial cardiomegaly and mild pulmonary congestion; N-terminal pro-brain natriuretic peptide (5698 ng/L) was substantially increased, and troponin T (56 ng/L) levels were slightly above reference values. Transthoracic echocardiography showed akinesis of the anteroseptal and apical segments with an ejection fraction reduced to approximately 20%. We diagnosed subacute myocardial infarction and initiated pharmacotherapy. On hospital day 7, coronary angiography revealed a left anterior descending artery lesion with 99% stenosis; percutaneous coronary intervention was successfully performed the next day. That same day, transthoracic echocardiography revealed a large mobile left ventricular apical thrombus without any left ventricular aneurysm, and heparin therapy was initiated. On hospital day 10, three-dimensional computed tomography confirmed the location of an apical thrombus, and we planned a fourth intercostal approach. A thrombectomy was performed on hospital day 11 using an endoscopic trans-mitral approach with a right thoracotomy to avoid a left ventriculotomy. The patient was discharged from intensive care on postoperative day 2 under heparin and warfarin therapy. The subsequent postoperative course was uneventful, and he was discharged on postoperative day 14 with a vitamin K antagonist. At the 6-month follow-up, there was no recurrence of thrombus in the left ventricle and Ejection Fraction had improved to 46%.ConclusionsTotally endoscopic thrombectomy via a trans-mitral approach through right thoracotomy was effective for a left ventricular thrombus. When concomitant coronary artery bypass grafting or left ventriculoplasty are not required, this procedure can be an effective option.

A new marker of coronary collateral flow in patients presenting with acute myocardial infarction.

Multimerin-2 is an adhesion substrate between pericytes and basal membranes during angiogenesis. The present study aimed to assess the relationship between serum Multimerin-2 and coronary collateral flow grade. Between April 2022 and August 2022, 88 patients with subacute ST-elevation myocardial infarction were included in this study. The main inclusion criteria were patients who present 12-48 hours after symptom onset and aged between 18 and 90 years. The patients were divided into two groups according to the Rentrop classification: poor collateral group (Rentrop grade 0-1) and good collateral group (Rentrop grade 2-3). Biochemical and hematological parameters were measured before coronary angiography. Serum Multimerin-2 levels were found to be significantly different between the two groups, and levels were higher in the Rentrop 2-3 group than in the Rentrop 0-1 group (3,527.9 ± 1,194.2 pg/ml and 946.7 ± 249.1 pg/ml; p < 0.00). Receiver operating characteristic curve analysis indicated that the area under the curve was 0.918 (p = 0.001), and the best cut-off value of 849 pg/ml had a sensitivity of 90.1% and a specificity of 84.1% for predicting Rentrop grade 2-3 coronary flow. The number of patients with low left ventricular ejection fraction (LVEF) by echocardiography at 30 days was significantly higher in patients with poor collateralization. Multimerin-2 levels were found to be higher in patients with Rentrop grade 2-3 coronary flow than Rentrop grade 0-1 coronary flow after myocardial infarction. We detected a potential relationship between MMR-2 and good coronary collateral formation.

P165 ARRHYTHMIC STORM IN SUBACUTE MYOCARDIAL INFARCTION: A CASE REPORT

Abstract Introduction Ventricular arrhythmias (VA) represent a common complication of myocardial infarction (MI). Typically, they occur in two scenarios: during acute MI, related to ongoing ischemia, as ventricular tachycardia (VT) or ventricular fibrillation (VF), or in the context of a late phase of MI, related to the presence of a scar, as monomorphic VT (mVT). Despite the above, their occurrence may be atypical. Clinical Case 55–year–old man affected by obesity, diabetes and hypertension, admitted to our department for subacute MI. Coronarography showed three–vessel disease with indication for surgical revascularization. Thirty hours after admission, in absence of symptoms, occurrence of cardiovascular arrest due to mVT, which degenerated into VF. After resuscitation, ECG and Echo findings did not change compared to those observed at admission, excluding the presence of current ischemia. A blood gas analysis excluded dysionias. Few minutes later, arrhythmic recurrence of mVT degenerated into VF. This was refractory to electrical and antiarrhythmic therapy and stopped only after percutaneous left stellate ganglion block (LSGB) and deep sedation. Then, emergency surgical revascularization was performed. In the early postoperative days, during weaning attempts from sedation and ECMO support, that had become necessary due to hemodynamic instability after surgery, numerous recurrences of mVT, regressed only after deepening of sedation, multiple external shocks, antiarrhythmic polytherapy, and LSGB. A new coronarography documented patency of coronary artery bypass grafts. On 6th postoperative day, discontinuation of deep sedation and weaning from circulatory support without recurrence of VA. The patient was discharged from the intensive care unit and started on a rehabilitation pathway. Conclusions mVTs are commonly related to the presence of a scar, formed late after MI, or to the context of ongoing ischemia in acute MI. However, it should be remembered that even during the subacute phase of MI, arrhythmic instability might still occur. The responsible mechanisms are not completely known but it can be assumed that, even in the absence of a new ischemic event, the process of scar maturation may have led to a transient proarrhythmic substrate, responsible for the arrhythmic storm. Further studies are needed to clarify the mechanisms of arrhythmogenesis in the subacute phase of MI.

Targeting myeloid cell coagulation signaling blocks MAP kinase/TGF-β1-driven fibrotic remodeling in ischemic heart failure.

Despite major advances in acute interventions for myocardial infarction (MI), adverse cardiac remodeling and excess fibrosis after MI causing ischemic heart failure (IHF) remain a leading cause of death worldwide. Here we identify a profibrotic coagulation signaling pathway that can be targeted for improved cardiac function following MI with persistent ischemia. Quantitative phosphoproteomics of cardiac tissue revealed an upregulated mitogen-activated protein kinase (MAPK) pathway in human IHF. Intervention in this pathway with trametinib improves myocardial function and prevents fibrotic remodeling in a murine model of non-reperfused MI. MAPK activation in MI requires myeloid cell signaling of protease-activated receptor 2 linked to the cytoplasmic domain of the coagulation initiator tissue factor (TF). They act upstream of pro-oxidant NOX2 NADPH oxidase, ERK1/2 phosphorylation, and activation of profibrotic TGF-β1. Specific targeting with the TF inhibitor nematode anticoagulant protein c2 (NAPc2) starting 1 day after established experimental MI averts IHF. Increased TF cytoplasmic domain phosphorylation in circulating monocytes from patients with subacute MI identifies a potential thromboinflammatory biomarker reflective of increased risk for IHF and suitable for patient selection to receive targeted TF inhibition therapy.

1121 USE OF IMPELLA 5.0 AS BRIDGE TO LVAD IN CARDIOGENIC SHOCK: REPORT OF TWO CASES

Abstract Background Left ventricle assist devices (LVAD) are an option in end stage heart failure (HF) as bridge to or alterative to heart transplantation. Adequate compensation of patient is key to obtain a good outcome. We report two cases of Impella 5.0 bridge to LVAD in patients with cardiogenic shock (CS) in which intra-aortic balloon pump (IABP) failed to obtain hemodynamic stability. Case series A) A 60 years old man developed CS after anterior myocardial infarction treated with primary PCI of left main coronary artery. At presentation patient was hypotensive with signs of hypoperfusion and pulmonary congestion: systemic blood pressure (SBP) 80/60 mmHg despite inotropic drugs, blood lactates 4 mmol/l, urine output of last 6 hours 0,4 ml/kg/h (INTERMACS 2). Echocardiography showed severe left ventricle disfunction with LVEF 15%, severe mitral regurgitation (MR) and sPAP 45 mmHg. Therefore, IABP was implanted. Right heart catheterization (RHC) showed pulmonary hypertension and high filling pressure with reduced cardiac output and increased pulmonary vascular resistance (mPAP 39 mmHg, CPWP 28 mmHg, CO 3 l/min, PVR 3.7 uW, PAPi 2.8); X-ray chest showed persistence of pulmonary congestion. After 9 days on IABP, patient underwent Impella 5.0 implant through right axillary artery as bridge to durable LVAD. Pulmonary artery catheter (PAC) monitoring showed reduction of pulmonary hypertension with mPAP 35 mmHg and CPWP 17 mmHg and chest X-ray documented improvement of lung congestion. Bedside rehabilitation was started. Two weeks later patient underwent LVAD HM3 implantation as destination therapy. The patient was discharge home on post-operative day 55. B) After subacute myocardial infarction with three-vessels disease, a 53 y.o. man developed severe congestive HF with severe left ventricular disfunction and was referred to our institution for evaluation. RHC showed pulmonary hypertension with pre-capillary component not reversible after enoximone test, contraindicating heart transplantation. Therefore, patient was candidate to receive LVAD as bridge strategy. Echocardiography at admission showed dilated and hypokinetic left ventricle (EDV 200 ml, LVEF 17% severe MR, sPAP 60 mmHg) and dilated and hypokinetic RV. During hospitalization the patient experienced CS with SBP 62/45 mmHg, 6-hours urine output of 1,4 ml/kg/h and blood lactates 8.3 mmol/l (INTERMACS 1) so femoral IABP was implanted. RHC was repeated both without IABP support (mPAP 37 mmHg, PCWP 28 mmHg, CO 1.4 l/min, CI 0.9 l/min/m2) and with IABP support (mPAP 32 mmHg, PCWP 18 mmHg, CO 2.15 l/min, CI 1.4 l/min/m2). During the following stay he developed S. Aureus sepsis requiring prolonged antibiotic therapy. Expecting a long time before LVAD, axillary Impella 5.0 was implanted in order to unload the LV and allow early patient mobilization. Subsequent PAC monitoring showed improvement of pulmonary hypertension and cardiac index (mPAP 24 mmHg, PCWP 9 mmHg, CO 5.1 l/min with Impella flow 4.2 l/min, CI 3.2 l/min/m2). After 11 days, patient received LVAD HVAD with uneventful course and was discharged on post-operative day 22. Conclusions Impella 5.0 is a surgically implanted intravascular microaxial blood pump that delivers up to 5 l/min of blood from LV to aorta, leading to improved perfusion and more efficient LV unloading. In patients with CS this can help to obtain better decongestion, RV recovery, and favorable preconditioning before LVAD implant. Moreover, axillary access allows better patient mobilization preventing cachexia after long time hospitalization.

ИЗМЕНЕНИЯ ЛИПИДНОГО ОБМЕНА В НАЧАЛЬНЫЕ ПЕРИОДЫ ИНФАРКТА МИОКАРДА, ОСЛОЖНЕННОГО ОСТРЫМ ПОВРЕЖДЕНИЕМ ПОЧЕК, У МУЖЧИН МОЛОДОГО И СРЕДНЕГО ВОЗРАСТА

Relevance. Changes in lipid metabolism during myocardial infarction (MI) complicated by acute kidney injury (AKI) are potentially important for evaluating the effects of therapy and expanding the possibilities of prevention. Aim. To evaluate the changes in lipid metabolism during acute and subacute MI periods and their role in the complication’s development in men under 60 years old (y.o.) with AKI to im-prove prevention and outcomes. Material and methods. The results of inpatient examination and treatment of men aged 20-60 y.o. with MI were studied. Patients were divided into two age-comparable groups: the study group, with AKI - 22 patients and the control group, without it - 141 patients. The parameters of lipid metabolism and their dynamics were compared in the first hours (1) and at the end of the third week of MI (2) in selected groups, their influence was assessed (risk analysis by Pearson's Chi-square test) on the risk of AKI development and complications MI in the study group. Results. In the study group, the following were observed: higher levels of low-density lipo-protein2 (LDL2) (5.53±2.50 mmol/l) compared to the control group (3.33±2.45 mmol/l; p=0.02); an increase in the levels of very low-density lipoproteins, a coefficient and an atherogenic index, a decrease in triglycerides (TG) at the end of the third week of the disease. The risk of AKI development was associated with the concentration of TG1≥1.88 mmol/l (p=0.007). Complicated course of MI in the study group is characterized by levels of LDL1≥4.0 (p=0.02), high-density lipoprotein1 (HDL1)˂1.1 (mmol/l; p=0.02), and their ratio (LDL1/HDL1) ≥4.5 (p =0.02). Conclusions. In AKI, persistent atherogenic changes in lipids are noted both in the acute and at the end of the subacute period of MI. The risk of developing AKI increases at levels of TG1≥1.88 mmol/l, and the complicated course of MI in the study group is associated with lev-els of LDL1≥4.0, HDL1˂1.1 (mmol/l) and LDL1/HDL1≥4.5. It is expedient to use them in predictive modeling.

К ВОПРОСУ ОБ ОСОБЕННОСТЯХ КАЧЕСТВА ЖИЗНИ МУЖЧИН МОЛОЖЕ 60 ЛЕТ С НАРУШЕНИЯМИ МОЧЕИСПУСКАНИЯ В ОСТРЫЙ И ПОДОСТРЫЙ ПЕРИОДЫ ИНФАРКТА МИОКАРДА

Relevance. Changes in the quality of life associated with heart failure (HF) in young and mid-dle-aged men with urological pathology and myocardial infarction (MI) are not well under-stood. Aim. To evaluate changes in the quality of life (QL) indicator associated with heart failure (HF) in men under 60 years old with MI and acute urinary retention (AUR) to improve prevention and outcomes. Material and methods. The study included men aged 19-60 years old with type I MI. Patients are divided into two age-comparable groups: I - the study group, with AUR - 22 patients; II - control, without it - 633 patients. A comparative analysis of the QL indicator associated with HF (HFQL) (V. Ironosov) was performed in the selected groups in the first 48 hours (I) and at the end of the third week (II) of MI. The changes and correlations (C. Spearmen) of HFQL with clinical features, metabolic parameters, central and peripheral hemodynamics were studied. Results. HFQL in patients with AUR (85.7±15.6%) was worse than in the control group (59.4±20.1%; р˂0.0001) in the first hours of MI. At the end of the third week of the disease, no differences between the groups were observed (24.3±11.9 and 18.6±11.9%, respectively; p = 0.06). A positive (72 and 69%) dynamics of HFQL were obtained from the first hours to the end of the subacute MI period in both patient groups (р˂0.0001). In the study group, signifi-cant correlations of HFQL with the size of the left heart chambers, parameters of left ventricle systolic and diastolic function, peripheral hemodynamic, and lipid metabolism parameters were revealed. In the control group, more correlations were found, but their strength was less. Conclusions. The quality of life associated with HF is worse in patients with AUR during the first hours of MI. Dilatation of the left heart chambers, left ventricle systolic and diastolic dys-function, no history of arterial hypertension, and hypocholesterolemia were the most associat-ed with quality of life in the study group. The assessment of HF-related quality of life is use-ful as an adjunct to the examination of patients with MI, starting from the first hours of the disease, for early identification of risk groups for adverse events and chronic HF formation.

Features of Cerebral Infarction Due to Left Ventricular Thrombus.

Objective Left ventricular (LV) thrombus is a rare condition in acute cerebral infarction. The prevalence and features of cerebral infarction with LV thrombus are unclear. We explored the features of cerebral infarction due to LV thrombus. Methods In this single-center retrospective study, we investigated consecutive patients with acute ischemic stroke admitted within seven days of the onset who had LV thrombus found by transthoracic echocardiography (TTE). First, we calculated the prevalence of LV thrombus in patients with cardioembolic stroke (CES). Second, we investigated the baseline characteristics, including the TTE findings and features of cerebral infarction due to LV thrombus. Results From June 2012 to January 2019, a total of 5,693 patients were enrolled. Of these, 1,408 (25%) patients were diagnosed with CES. Of these 1,408 patients with CES, 13 (0.9%) had LV thrombus indicated by TTE, with dilative cardiomyopathy, subacute myocardial infarction, and old myocardial infarction present in 1 (8%), 2 (15%), and 10 (77%), respectively. The ejection fraction (EF) was 48.9% (25.3-64.7%). The maximum longitudinal size of LV thrombus was 13.4 (0.97-38.1) mm, and there was no correlation between the size of the LV thrombus and the EF. Regarding the features of cerebrovascular infarction, major vessel occlusion was observed in 10 (77%) patients. Six (46%) patients were found to have good outcomes (modified Rankin Scale 0-2) at 90 days after the onset. Conclusion LV thrombus was seen in 0.9% of patients with CES. Many of the patients with LV thrombus had major vessel occlusion.

HEART RHYTHM AND CONDUCTIVITY DISTURBANCES IN MEN UNDER 60 YEARS OLD WITH ACUTE KIDNEY INJURY DURING MYOCARDIAL INFARCTION

Abstract: Relevance. Acute kidney injury (AKI) and arrhythmias negatively affect the prognosis of myocardial infarction (MI). Aim. To evaluate the features of heart rhythm and conduction disturbances and electrocardiographic changes in men under 60 years old (y.o.) with AKI in MI to improve understanding of the mechanisms of development and prevention. Material and methods. The study included men aged 19-60 years old with MI and AKI were studied. The patients were divided into two age comparable groups: I - study group, with AKI - 25 patients; II - control, without it - 486 patients. A comparative analysis of the frequency of observation of arrhythmias and ECG changes in the selected groups, analysis of the influence of various factors (Pearson's Chi-square) on the risk of arrhythmia in the study group were performed. Results. The compared groups did not differ in the frequency and structure of cardiac arrhythmias and conduction disorders. For the development of arrhythmias in the study group, the most important were: diastolic (absolute risk (AR): 100%; relative (RR) - 5.3; p = 0.02) 120 mm Hg. and more and systolic (AR: 83.3%; RR: 5.3; p = 0.02) blood pressure (BP) 180 mm Hg or more, the early and late left ventricular (LV) filling velocity relationship less than 0,7 (AR: 66.7%; p = 0.002), left atrial 38 mm or more (AR: 53.3%; p = 0.007), LV end-systolic volume index (52.4 ml / m2 or more) and LV end-diastolic index (88.0 ml / m2 and more) (AR: 66.7% each; RR: 4.67 each; p = 0.01). For the development of life-threatening arrhythmias (ventricular fibrillation and asystole) in the study group, a body weight of 110.0 kg or more was of additional importance (AR: 50.0%; p = 0.01). New arrhythmias in the subacute MI period were recorded only in the control group of patients. Conclusions. For AKI in MI in men under 60 y.o., there were no specific heart rhythm and conduction disturbances. For the arrhythmias development in MI with AKI, signs of pronounced hypertension, dilatation of the left heart and LV systolic and diastolic dysfunction are primary importance. Obesity is an additional importance for the life-threatening arrhythmias development in MI with AKI.

Investigation of the fabomotizol dihydrochloride effect on the morphological picture of the heart left ventricle in rats with the subacute myocardial infarction

The purpose of the study. Investigation of the effect of the fabomotizol dihydrochloride systematic therapy on the morphological picture of the heart left ventricle (LV) in rats in the subacute period of myocardial infarction. Materials and methods. Myocardial infarction (MI) modeling was carried out using the A.Selye method. Fabomotizol dihydrochloride was administered to rats intraperitoneally 1 time per day from the 15th to the 28th day after MI at a dose of 15 mg/kg. At the end of the experiment, euthanasia and a pathoanatomic autopsy were performed. Samples of hearts after fixation in formalin and standard wiring were poured into paraffin blocks. Histological sections of the hearts were microscoped in transmitted light. Results. Dilation of the LV cavity and thinning of its walls in animals treated with fabomotizol dihydrochloride are less pronounced than in control rats with MI. In the periinfarction zone of the myocardium in rats treated with fabomotizol dihydrochloride, wave-like deformation and fragmentation of cardiomyocytes is less intense, and the transverse striation of myofibrils, on the contrary, is more pronounced than in the control. In animals treated with fabomotizol dihydrochloride, the periinfarction zone is well vascularized. Conclusion. According to the results of morphological studies performed on a model of subacute MI in rats, it was demonstrated that systematic therapy with fabomotizole dihydrochloride contributes not only to a significant reduction in the necrosis zone, but also to a certain extent prevents the development of early postinfarction remodeling. In rats treated with fabomotizol dihydrochloride, in contrast to control animals, reparative processes prevail in the cardiac muscle. These observations indicate the presence of cardioprotective activity in the drug.

LIPID METABOLISM STATE IN MEN UNDER 60 YEARS OLD WITH METABOLIC SYNDROME DURING MYOCARDIAL INFARCTION

Abstract: Relevance. The lipid metabolism changes during myocardial infarction (MI) in men with metabolic syndrome (MS) may be important for the MI complications development. Aim. To evaluate the lipid metabolism changes in acute and subacute MI periods and their role in the MI complications development in men under 60 years old with MS to improve prevention and outcomes. Material and methods. The study included men aged 19-60 years old with MI and MS. The patients were divided into two age-comparable groups: I - study group, with MS - 95 patients; II - control, without it - 571 patients. A comparative analysis of the lipid metabolism parameters and their dynamics in acute and subacute MI periods in selected groups, analysis of their influence on the risk of MI complications were performed. Results. It was found that in the first hours of MI in the study group, higher levels of triglycerides (3.19 ± 2.34 mmol/l) were noted compared to the control group (2.44 ± 1.75 mmol/l; p=0.02). The dynamics of lipid metabolism at the end of the third week of MI, significant multidirectional changes in all parameters with more pronounced atherogenic changes in the study group were revealed. The risk of MI complications was associated with levels of triglycerides (TG) ˂5.2 (p=0.02), high density (HDL) ≥0.9 (p=0.04) and very low-density lipoproteins (VLDL) ˂0.9 (p=0.04) (mmol/l) of the first hours of MI. Conclusions. The presence of MS impairs lipid metabolism in both acute and the subacute MI periods. In the study group, there is an increase in the levels of atherogenic lipids and their indices during the observation period. MI complications are associated with levels TG ˂5.2; HDL ≥0.9 and VLDL ˂0.9 (mmol/l) during the first hours of MI. It is expedient to use them in predictive modeling.

Methods for Transepicardial Cell Transplantation in a Swine Myocardial Infarction Model.

The transplantation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has garnered significant attention as a potential means of restoring lost muscle mass and contractile function in injured hearts. Early preclinical work with hPSC-CMs employed rodent models, but the field has recently advanced to transplantation studies in more translationally relevant large animal models including non-human primates and swine. The pig is a particularly attractive model for such studies because the size, structure, and physiology of the porcine heart is very similar to that of humans. The pig model has reasonably high throughput, is readily amenable to clinically available cell delivery methods and imaging modalities and has been used frequently to test the safety and efficacy of new cardiac therapies. Here, we describe methods that were established in our laboratory for the specific purpose of testing hPSC-CM transplantation in a pig model of subacute myocardial infarction, but these same techniques should be broadly applicable to the transepicardial delivery of other biologicals including other candidate cell populations, biomaterials, and/or viral vectors.

483 Minoca in a young patient with elevated platelet count

Abstract Aims Ischaemic heart disease is rare in young women, especially in the absence of a positive family history and strong cardiovascular risk factors, such as insulin-dependent diabetes. However, the correct diagnosis of ischaemic heart disease in young population is mandatory, and the specific aetiology should be identified to ensure a proper treatment. Methods and results We present the case of a 35-year-old caucasian woman who underwent ambulatory cardiological evaluation after episodes of chest pain and worsening dyspnoea (NYHA class II). The patient was asymptomatic at rest, BP was normal, heart rate was 80/minute in sinus rhythm, with no clinical signs of acute heart failure. ECG showed sinus rhythm with Q wave (lead DIII) and negative T waves (inferior leads). At echocardiographic evaluation LV was severely dilated (EDVi 105 ml/mq, EDD 66 mm) with akinesia and scar in the infero-posterior wall determining moderate reduction in ejection fraction (LVEF 40%), associated with secondary moderate mitral regurgitation; the right ventricle, the other valves and the aortic root were normal. The young lady was then admitted to Cardiology Unit for further investigations. She underwent cardiac MRI, which confirmed LV dilatation and dysfunction (EDV 198 ml/mq, LVEF 42%), associated with akinesia and infero-postero-lateral wall scar, with transmural myocardial fibrosis in the same segments, and subendocardial fibrosis on the basal segment of the anterior wall. Analysis of blood samples revealed elevated haemoglobin levels (Hb: 17.5 g/dl, n.v. 12–16 g/dl) and extremely elevated platelet count (PLT 945 000/mmc, n.v. 130 000–400 000/mmc). Cardiac troponin I (cTnI) was negative on serial determinations. All findings were suggestive for subacute infero-posterior myocardial infarction. Coronary angiography was performed via radial access: the exam was negative for significant stenosis in any coronary segment, only mild stenosis of proximal dominant left circumflex (LCX) artery was identified; moreover, there were no angiographic signs of coronary dissection. Eventually, SCAD and aortic defects were ruled out by coronary CT scan, which was negative for both coronary and aortic dissection. New blood samples examinations confirmed high values of Hb and PLT. Low levels of EPO (1.4 mU/ml) and JAK-2 mutation V617F positivity suggested the clinical diagnosis of essential thrombocythemia, later confirmed by bone marrow aspiration. Hydroxyurea was prescribed, as well as haematologic follow-up. Conclusions This is an interesting case of ischaemic heart disease, confirmed by ECG, echocardiography, and cardiac MRI, in presence of non-obstructive coronary artery disease. The aetiology of this specific case of MINOCA is potentially to be sought in the haematologic disorder. It is possible to hypothesize that a platelet/RBC clot might have determined acute obstruction of the proximal dominant LCX artery, then followed by spontaneous recanalization. Only mild stenosis on the proximal vessel was identified, and stenting was considered not appropriate for this lesion.

593 Spontaneous coronary artery dissection in young

Abstract Aims We present the case of a 25 years-old patient, presented to the Emergency Department for chest pain and epigastralgia complicated by vomiting. Symptoms started about 30 h before, afterwards an effort. The patient did not have any known cardiovascular risk factors (except for sporadic consumption of cannabis) and family medical history was negative for premature cardiovascular disease or sudden cardiac death. His past medical history was unremarkable. Methods and results Clinical examination was normal. ECG was suggestive for subacute anterior ST-elevation myocardial infarction (QS in V1–V4 leads with ST segment elevation and biphasic T-waves in V4–V6) and was accompanied by significant elevation of myocardial necrosis biomarkers (hsTnT 3416 ng/l, n.v. &amp;lt;15). Echocardiography revealed a severely reduced left ventricular ejection fraction (LVEF = 30%) with regional wall motion abnormalities (apical and septal akinesia, and anterior mid-ventricular segment hypokinesia). Coronary angiography was suggestive for a dissection of the proximal-to-mid left anterior descending artery. Dissection flap, subocclusion of the first septal branch, and intramural thrombosis were noted. Direct stenting with drug-eluting stent was successful, with thrombolysis in myocardial infarction (TIMI) flow grade 3. The patient was started on dual antiplatelet treatment (aspirin and ticagrelor), ACE-inhibitors, beta blockers, and spironolactone. Further testing ruled out other conditions that may be associated with spontaneous coronary artery dissection (autoimmune diseases, including vasculitis, connective tissue disease, coagulative disorders). The clinical course was complicated by pericarditis and the development of LV apical thrombus. So, patient was started on anticoagulation (warfarin) with subsequently downgrading from ticagrelor to clopidogrel. Echocardiographic follow-up documented a progressive improvement of LVEF (50%), and global longitudinal strain (GLS −15%) with persistence of wall motion abnormalities in the apical and septal segments. Partial resolution of intracavitary thrombi was documented. CMR revealed LV apical aneurysm. Moreover, the use of dedicated sequences showed transmural late gadolinium enhancement in akinetic segments, and fatty metaplasia of the apical portion of the anterior wall and anterior septal wall. Finally, early gadolinium enhancement imaging, confirmed the persistence of LV stratified apical thrombus. Conclusions Spontaneous coronary artery dissection (SCAD) is an underdiagnosed and frequent cause of acute coronary syndrome (ACS) in young-to-middle aged patients, particularly women; therefore, even in young people, a chest pain episode suggestive for an ischaemic cause should never be underestimated. Cardiac magnetic resonance is the most accurate method to evaluate the sequelae of myocardial infarction (including LV size and function, presence of fatty metaplasia, extent and transmurality of ischaemic scar, presence of thrombi), to aid in differential diagnosis and to define prognosis and guide the therapeutic management.

Abstract #1088797: Graves' Disease Induced Vasospastic Angina and NSTEMI: An Unusual Link Between Endocrinology and Cardiology

A common link between Endocrinology and Cardiology is T3, the active form of thyroid hormone. Approximately 5-25% of patients with hyperthyroidism have atrial fibrillation, but a far less common cardiovascular disease (CVD) associated with thyrotoxicosis is myocardial infarction (MI). There are few reported cases of hyperthyroidism causing STEMI, NSTEMI, coronary vasospasm, and autoimmune myocarditis. We present a previously healthy 58-year-old female seen at the emergency department (ED) for nighttime/early morning chest pain, dyspnea and diaphoresis. She denied prior episodes or family history of CVD. EKG showed incomplete right bundle branch block and anterior T-wave inversions. Troponin peaked at 13 ng/mL. Echocardiogram was unremarkable. Left heart catherization demonstrated non-obstructive coronary artery disease concerning for vasospasm. Pertinent laboratories showed decreased TSH (< 0.005 μU/mL) and elevated total T3 and free T4 (2.19 ng/dL). Differentials for thyrotoxicosis included primary hyperthyroidism, spurious results (patient was taking supplement with biotin and iodine), and stress-induced thyroid function alteration. Further workup revealed negative Thyroid Stimulating Immunoglobulin (TSI) and positive TSH Receptor Antibodies (TRAb). Chest pain resolved and she was discharged, but returned days later with same complaints and elevated troponin. Cardiac differentials were myocarditis in the setting of autoimmune thyroiditis vs vasospastic angina. Serial EKGs had no signs of myocarditis. She denied prior viral infection, autoimmune conditions, recreational drugs, appetite suppressants, ephedrine, or migraine medications. Cardiac MRI was not consistent with myocarditis, instead suspicion was raised for subacute MI with nonobstructive coronary arteries (MINOCA). Based on Coronary Vasomotion Disorders International Study Group (COVADIS) criteria, she had nitro-sensitive vasospastic angina. In the setting of thyrotoxicosis and positive TRAb, she was diagnosed with coronary vasospasm NSTEMI triggered by Graves'. Autoimmune thyroid disease may be undiagnosed 50% of the time, unknowingly contributing to CVD. T3 has direct and indirect cardiovascular effects. It promotes catecholaminergic stimulation and acts as a positive ionotrope and chronotrope. Excess T3 creates a hypermetabolic state that can rarely trigger severe coronary vasospasm. MI with < 50 % stenosis is defined as MINOCA, accounting for 6% of acute infarctions that undergo angiography. Non-atherosclerotic etiologies of MINOCA include coronary vasospasm, embolism/thrombus, anemia, hypotension, and thyrotoxicosis. Our patient had two of these, and to the best of our knowledge, this is the first reported case of a troponin >0.5 ng/mL secondary to Graves’ disease induced MINOCA.

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization and cardiovascular drugs, a significant proportion of patients develop pathological left-ventricular remodeling and progressive heart failure following MI. Therefore, new therapeutic options, such as cellular and gene therapies, among others, have been developed to repair and regenerate injured myocardium. In this context, animal models of MI are crucial in exploring the safety and efficacy of these experimental therapies before clinical translation. Large animal models such as swine are preferred over smaller ones due to the high similarity of swine and human hearts in terms of coronary artery anatomy, cardiac kinetics, and the post-MI healing process. Here, we aimed to describe an MI model in pig by permanent coil deployment. Briefly, it comprises a percutaneous selective coronary artery cannulation through retrograde femoral access. Following coronary angiography, the coil is deployed at the target branch under fluoroscopic guidance. Finally, complete occlusion is confirmed by repeated coronary angiography. This approach is feasible, highly reproducible, and emulates the pathogenesis of human non-revascularized MI, avoiding the traditional open-chest surgery and the subsequent postoperative inflammation. Depending on the time of follow-up, the technique is suitable for acute, sub-acute, or chronic MI models.

Differences in the Treatment of Acute Coronary Syndrome in the Pre-COVID and COVID Era: An Analysis from Two German High-Volume Centers.

The COVID-19 pandemic is placing a heavy burden on healthcare systems worldwide with the risk that acute cardiovascular diseases are treated too late. The present study aims to analyze patients with acute coronary syndrome in the current pandemic. A total of 966 patients (2019 n = 463, 2020 n = 503) can be evaluated. A comparison of patient care during and before the COVID-19 pandemic was made in terms of patient characteristics and pre- and in-hospital processes. Another aim is to show how many patients seek clinical care at a late stage of the disease. After Lockdown in Germany at week 12, 2020, there was a significant decrease in patients with an acute coronary syndrome (ACS), significant for STEMI cases in the first weeks after Lockdown (calendar week 13–16 2019 n = 43, 2020 n = 30; p = 0.02). The time from pain to first medical contact (time to FMC) is significantly extended during Lockdown, while internal clinical processes are unchanged. The rate of subacute myocardial infarction is numerically, but not significantly increased in calendar weeks 15, 2020 (p = 0.40) and 16 (p = 0,19). In addition, elderly patients avoid treatment for multifactorial reasons, and the longer overall pain to FMC may impact long-term mortality.