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Aims We aimed to investigate the long-term cardio-protective effect associated with beta-blocker (BB) treatment in stable, optimally treated myocardial infarction (MI) patients without heart failure (HF). Methods and results Using nationwide registries, we included patients with first-time MI undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) during admission and treated with both acetyl-salicylic acid and statins post-discharge between 2003 and 2018. Patients with prior history of MI, prior BB use, or any alternative indication or contraindication for BB treatment were excluded. Follow-up began 3 months following discharge in patients alive, free of cardiovascular (CV) events or procedures. Primary outcomes were CV death, recurrent MI, and a composite outcome of CV events. We used adjusted logistic regression and reported standardized absolute risks and differences (ARD) 3 years after MI. Overall, 30 177 stable, optimally treated MI patients were included (58% acute PCI, 26% sub-acute PCI, 16% CAG without intervention). At baseline, 82% of patients were on BB treatment (median age 61 years, 75% male) and 18% were not (median age 62 years, 68% male). BB treatment was associated with a similar risk of CV death, recurrent MI, and the composite outcome of CV events compared with no BB treatment [ARD (95% confidence intervals)] correspondingly; 0.1% (−0.3% to 0.5%), 0.2% (−0.7% to 1.2%), and 1.2% (−0.2% to 2.7%). Conclusions In this nationwide cohort study of stable, optimally treated MI patients without HF, we found no long-term effect of BB treatment on CV prognosis following the patients from 3 months to 3 years after MI admission.

Purpose To investigate the impact of coronary anatomy and pPCI parameters on the most prognostically significant MRI measures of acute MI with ST segment elevation (MVO, infarct size). Methods The study included 52 patients with STEMI and primary percutaneous coronary intervention (pPCI) of infarct-related arteries (IRA). On Days 3–7 contrast-enhanced cardiac MRI was done. Tissue analysis of scans was performed evaluating infarct size, presence and size of MVO. Results The study included 52 patients with first STEMI within 3 hours of symptom onset EF was 49.0±11.0%, and in the comparator group – 45.7±10.5%, p=0,2). MRI-measured infarct size was significantly higher in the group where pPCI was done >3 hours of symptom onset: 18.1±1.7% of the LV mass, compared to the early reperfusion group – 10.9±1.9% (p=0.009). MVO magnitude was also higher in the later pPCI group (2.6±0.64% vs 0.03±0.3% in the comparator group), (p Complete occlusion of IRA was associated with higher IS (16,97±3.3 vs 12.05±1.4, p=0.02). There was no reliable correlations between IRA patientcy and MVO magnitude (p=0.7). Conclusions In this study pPCI timing, in groups of below and more than 3 hours after symptom onset, had no significant impact on EF, as determined by MRI. However, pPCI timing exceeding 3 hours significantly influenced infarct size, the occurrence and magnitude of microvascular obstruction. LAD being the IRA was associated with larger IS, higher risks of MVO development. Patient IRA was associated with smaller IS as determined by MRI. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Healthcare Russian Federation

Background Assessment of right ventricular (RV) function by transthoracic echocardiography (TTE) in acute pulmonary embolism (PE) has an essential role to severity stratification. However, there is no reliable information on RV function about the clinical utility of advanced TTE parameters in follow-up. Purpose We aimed to assess the clinical utility of 3D RV ejection fraction (3DEF) and free wall longitudinal strain (FWLS) compared to conventional parameters in evaluating RV function in patients with acute PE at time of diagnosis and after follow-up and the relation with adverse outcomes. Methods We prospectively recruited 86 patients with intermediate-high and high-risk bilateral PE from 2018 to 2020 in our centre. Patients underwent TTE during admission and at 6 to 12 months follow-up that included conventional RV parameters (pulsed Doppler S wave (S'), TAPSE, and fractional area change (FAC)). 3DEF and FWLS were obtained as well. Normal values were stablished according to European guidelines. Results Mean age was 63.7±16.5 years, 58% males. Reperfusion treatment was performed in a 26,8%. In-hospital mortality was 4,7% (3 patients in the acute phase of PE and 1 due to rePE. The median follow-up was 1.3 years (IQR 1–2.5). 9 patients died (2 due to PE, 3 due to respiratory failure and 5 due to cancer). Patients with adverse events had a greater severity in PESI scale and worse RV function assessed by 3DEF and 3D volumes. There were no significant differences between groups in FAC, S' and TAPSE (Table 1). Baseline echocardiographic parameters were analyzed in the acute phase during admission and at 6–12 month follow-up (Table 2). There was a significant improvement in conventional parameters (TAPSE and FAC) and a reversal of FWLS values (P=0,01) at follow-up. 3DEF improved, but was not statistically significant (p=0,06). There was a greater reversal in end-systolic volume compared to end-diastolic volume. Conclusion Advanced RV function assessment by 3DEF and FWLS is useful in the acute phase and follow-up. FWLS showed and early normalization after PE resolution, whereas 3DEF improved but remained pathological at 6–12 months follow-up. Funding Acknowledgement Type of funding sources: None. Table 1Table 2

Background The clinical outcome of myocardial ischaemia/reperfusion (I/R) injury is still unpredictable and detrimental despite the use of several agents including renin-angiotensin system inhibitors. Quercetin (QN), one of the most prevalent flavonoids, has attracted great attention in the recent years due to its protective role against I/R injury. Interestingly, a recent experimental study showed an important role for β-catenin in the regulation of myocardial I/R injury following heterotopic heart transplantation. Purpose The present investigation was directed to estimate the role GSK-3β/β-catenin signaling as a possible mechanistic pathway, through which QN could modulate the therapeutic effect of telmisartan (Tel) in myocardial I/R injury in rats. Methods Myocardial I/R was induced by ligation of the left descending coronary artery for 30 min followed by reperfusion for 2 h. Rats were pretreated with Tel (12 mg/kg/day, po), QN (25 mg/kg/day) or a combination of both agents for 3 days before the experiment. Electrocardiographic abnormalities were assessed at the end of ischemic and reperfusion periods. Animals were then sacrificed to assess the cardiac injury surrogate markers; viz., serum CK-MB and cTn-I levels and cardiac energy content (ATP) as well as oxidative stress (ROS, MDA, SOD and TAC), inflammation-related (TNF-α, NF-κB, ICAM-1 and MPO) and apoptotic markers (caspase 3 and Bcl-2). Moreover, the hallmark of fibrosis (TGF-β1) was estimated in addition to GSK-3β/β-catenin signaling. Finally, histological examinations were performed to assess the severity of myocardial damage. Results Combined Tel/QN therapy showed an additional improvement compared to each therapy alone (p Funding Acknowledgement Type of funding sources: None.

Background Left ventricular thrombus (LVT) is a potential complication of acute myocardial infarction and is associated with a high rate of thromboembolic events. With the advent of more potent antithrombotic medications and quicker reperfusion strategies, the incidence of LVT has been reduced. However, current guidelines recommendations are based on older evidence and some aspects of the treatment are being questioned, such as the optimal duration of anticoagulation. Purpose To determine how length of anticoagulation influences the risk of thromboembolic events and mortality in a tertiary-care cardiac center with primary percutaneous coronary intervention (PCI) capability. Methods A cohort of consecutive cases of patients with IVT diagnosed by transthoracic echocardiography between 2014 and 2020 was retrospectively analyzed. Results A total of 72 cases of LVT were identified. Etiology was ischemic cardiomyopathy in 60 (82.0%) patients and 13 (20.0%) were female. LVT was diagnosed in the setting of acute myocardial infarction in 23 (32.0%) of cases. Prolonged anticoagulation regimes were significantly associated with fewer systemic thromboembolic events (21.4% vs 6.1%; p=0.04), without a significant effect on mortality (Figure 1). Conclusion Clinical manifestations and epidemiology of LVT has recently changed after the advent of improved treatments. In our cohort, an indefinite anticoagulation strategy was significantly associated with fewer thromboembolic events, suggesting that future investigations should clarify these issues. Funding Acknowledgement Type of funding sources: None.

Background The left circumflex artery (LCX) and its branches are less often recognized as infarct related artery (IRA) in STEMI compared to NSTEMI patients because of lower ability to detect posterior AMI on 12leads ECG. Significant proportion of patients with acute LCX occlusion therefore did not receive immediate reperfusion therapy. The recent ESC guidelines recommendation of immediate coronary angiography for NSTEMI with ongoing ischemia should change the situation. Objectives To estimate the change in proportion of patients receiving immediate reperfusion therapy for acute LCX occlusion within last 20 years. Methods Prospective registry of patients with acute coronary syndromes treated in the cardiac centre. The group of patients treated with direct PCI as STEMI and the group of patients treated as NSTE ACS were compared. Results Of 369 STEMI patients treated with primary PCI in 1995–2000, the LCX was recognized as IRA in only 29 (8%) patients. In the group of 809 STEMI patients treated in period 2008–2011, the LCX was detected as IRA in 133 (16%). In he recent group of 1006 patients treated as STEMI in period 2016–2019 the LCX was IRA in 166 (16.5%) patients. LAD, LM and RCA were detected as IRA in 407 (40.5%), 17 (1.7%) and 415 (41%) patients respectively. In the parallel group of 1087 NSTE-ACS patients the proportion of LCX, LAD, LM and RCA as culprit artery was 271 (25%), 438 (40%), 52 (5%) and 326 (30%) respectively. The difference of LCX involvement in STEMI (16%) compared to NSTE-ACS patients (25%) was highly significant (p Conclusion The disproportion of LCX involvement among the patients with STEMI and NSTE-ACS is not decreasing in the course of last 10 years. Our data show that still significant part of patients with acute LCX occlusion are diagnosed as having NSTE-ACS and are not treated with adequate immediate reperfusion. So even in recent era of modern reperfusion therapy these patients which mostly suffer posterior AMIs have a lower chance to receive the proper treatment in our region. The new ESC guidelines did not change this fading yet. Better diagnostics of AMI due to the acute LCX occlusion (including 15 leads ECG) is routinely needed or every suspected NSTEMI patient should undergo the acute coronary angiogram as he would be a STEMI patient. Funding Acknowledgement Type of funding source: None

Objectives To assess the evolution of in-hospital management of ST Segment Elevation Myocardial Infarction (STEMI) over the years in Portuguese hospitals and its impact on in-hospital complications and mortality Methods A nationwide electronic prospective registry that included all patients admitted to Portuguese hospitals with a diagnosis of acute coronary syndrome since 2002 until 2019 was used to collect all data relative to patients admitted with a STEMI diagnosis during that time frame. Data on demographic data, clinical data, revascularization strategy, medication during hospitalization. We compared the data and its evolution over the years to assess for trends. For statistical analysis, Qui-square tests were used to assess tendencies in categorical variables, and Kruskal-Wallis tests were used to assess tendencies in numerical variables. A p-value Results During the study, a total of 24425 patients were admitted for STEMI in Portuguese hospitals, 74.3% were male and average age of 63.9±13.6 years. We report a progressive increase in patients treated with aspirin, P2Y12 inhibitors (from 22.2% to 97.6% – p There was an increase of the use primary coronary angioplasty (36.4% to 73.2% – p Less patients had moderate to severely impaired left ventricle ejection fraction (28.8% to 14.9% – p Conclusion In 17 years, we report a progressive evolution of the in-hospital treatment of STEMI patients in Portuguese hospitals, with a higher prescription of guideline recommended medications, use of invasive reperfusion techniques and last generation stents, resulting in a lower rate of in-hospital complications and mortality. In-hospital outcomes over the years Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Registo Nacional de Síndromes Coronárias Agudas - Sociedade Portuguesa de Cardiologia

Background There is ongoing controversy and limited data about the optimal timing to perform delayed percutaneous coronary intervention (PCI) in stable ST-segment elevation myocardial infarction (STEMI) patients who have missed opportunities for acute reperfusion therapy and are in absence of ongoing ischemia. Purpose To evaluate the effects of timing of delayed PCI on short- and long-term safety outcomes in stable STEMI patients. Methods A cohort of 3,048 stable STEMI patients without acute reperfusion therapy who underwent delayed PCI were included in the study. Procedural timing was stratified into three groups: 7d. Primary outcomes were 30-day and 12-month major adverse cardiac events (MACE), a composite of death and reinfarction. Multivariate logistic and Cox regression models were performed. Results After multivariate adjustment, restricted cubic splines revealed a monotonic decrease in the risk of MACE with prolonged procedural timing (Figure-1). Delayed PCI on 3–7d and >7d were strongly associated with lower risks of MACE at 30 days (3–7d: Hazard ratio (HR) 0.43 [95% Confidence interval (CI) 0.18–0.99], P=0.046; >7d: HR 0.40 [95% CI 0.19–0.87], P=0.020) and 12 months (3–7d: HR 0.49 [95% CI 0.25–0.95], P=0.036; >7d: HR 0.42 [95% CI 0.22–0.77], P=0.006) compared with that on 7d also showed improvement in 12-month mortality (HR 0.45 [95% CI 0.22–0.91], P=0.026) over that on Conclusion Delayed PCI over a week after symptom onset had significant improvement in short- and long-term safety in stable STEMI patients especially with anterior MI or cardiac insufficiency. Decision-making on optimal timing should identify the high-risk individuals and balance between ischemic benefits and safety. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Twelfth Five-year Science and Technology Support Projects by Ministry of Science and Technology of China.

Background and purpose European and American cardiovascular treatment guidelines advocate for two and three years of beta-blocker (BB) treatment, respectively, following myocardial infarction (MI). Contemporary continued efficacy of longer-term use of BB in stable coronary artery disease has been debated in the era of reperfusion. We aim to investigate the cardio-protective effect associated with BB treatment in patients following MI. Methods Using nationwide databases, we included optimally treated patients with first-time MI undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) during admission and treated with both acetyl-salicylic acid and statins post-discharge between 2003 and 2017. Patients with prior history of MI, BB use or any other possible indication or contraindication for BB treatment (heart failure, cardiac arrhythmias or procedures, asthma, chronic obstructive pulmonary disease) were excluded. Continued BB exposure was defined as two redeemed prescriptions within the first 180 days following discharge, one of them within 90 days. Follow-up began 180 days following discharge in patients alive and with no further cardiovascular events or procedures prior. Patients were followed for a maximum of three years. Primary outcomes were cardiovascular death and recurrent MI in patients stratified by BB treatment using adjusted Cox regression models. Results A total of 27,068 patients optimally treated for MI were included (57% acute PCI, 26% sub-acute PCI, 17% CAG without intervention). At study start 180 days following MI, 79% of the patients were on BB treatment (median age 61 years, 75% male) and 21% were not (median age 62 years, 69% male). Cumulative incidence of cardiovascular death and recurrent MI did not differ significantly comparing patients on BB treatment with patients not on BB treatment (Figure). In multivariable analyses, BB treatment was associated with a similar risk of cardiovascular death and recurrent MI compared to the patients not receiving BB treatment (hazard ratios with [95% confidence intervals] correspondingly; 0.89 [0.68–1.17] and 1.02 [0.89–1.18]) (Figure 1). When stratifying the cohort according to calendar year and type of procedure during admission, we found similar results as the main analysis. No interaction for sex was found. Conclusions In this nationwide cohort study of optimally treated patients following MI at 180 days in the reperfusion era, we found a very good prognosis with only 1.2% suffering cardiovascular death and 4.7% suffering a recurrent MI within three years. In total 79% of patients were receiving BB treatment, but we found no difference suggesting BB to be associated with an improved cardiovascular prognosis. These findings challenge current clinical practice and guideline recommendation, suggesting that the role of long-term BB use may be obsolete among optimally treated MI patients. Further investigations, preferably a randomized trial, are warranted. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Ib Mogens Kristiansens Almene Fond, Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens Fond

Background The CAMI-1 study dealt with the depletion of CRP by apheresis in patients with acute myocardial infarction (AMI). CRP, the prototype human acute phase protein, has been known as a marker of poor prognosis in AMI and independently predicts 30-day mortality. Methods 66 STEMI patients were enrolled in the study following complete coronary revascularization (2–12 h after the onset of symptoms). 32 patients received CRP apheresis, whereas 34 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. In case of a rapid increase in CRP plasma levels following the 2nd session, a 3rd session was carried out another 24 h later. A specific CRP adsorber removed up to 79% of the original CRP. In each apheresis session, 6000 ml of plasma was treated via peripheral venous access. Primary study endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (CMR) 2–9 days after STEMI. Results Aphereses sessions were well tolerated with no relevant side effects. Peak CRP plasma levels after STEMI ranged from 9 to 279 mg/l. The expected peak CRP level after AMI can be calculated precisely with 2–3 CRP quantifications during the first 24 h after the onset of symptoms. The regression coefficient for this analysis is 0.91. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP peak levels. The statistical evaluation shows that the CRP concentration is significantly associated with the damage (infarct size, LVEF, circumferential strain) in the controls. This association was lost in the aphereses patients: they performed significantly better at all endpoints (infarct size, LVEF, circumferential strain) than the controls. The CRP apheresis significantly reduced myocardial damage. To our surprise, two apheresis patients had an infarct size of 0%. Conclusions For the first time we find an unequivocal association between myocardial infarct size and the CRP concentration. This is in some respects a surprise, since the basic assumption in AMI is that the vascular occlusion leads to primary damage and the reperfusion to secondary damage, which would not have led one to expect such a clear dose-response relationship as that observed here. In addition, our results show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis is now being further evaluated as a therapeutic approach in the treatment of acute myocardial infarction in a registry (CAMI registry). Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Pentracor GmbH

Background There is a high need for real-world international comparisons of management of patients with acute myocardial infarction. In Europe Estonia, Hungary, Norway and Sweden are among the few countries with national ongoing acute myocardial infarction registries with a high degree of completeness of data. Purpose To compare the management and outcome of hospitalized ST-segment elevation myocardial infarction (STEMI) patients in four European countries with a national ongoing myocardial infarction registry. Methods We compared patient baseline characteristics, use of in-hospital procedures and medications at discharge as well as 30-day and 1-year mortality for all patients admitted with STEMI during 2014–2017 using EMIR (Estonia; n=4,584), HUMIR (Hungary; n=23,685), NOMIR (Norway; n=12,414; data available for years 2013–2016) and SWEDEHEART (Sweden; n=23,342). Country-level results were compared as aggregated data. Results Mean age ranged from 65 to 69 years (table 1). Estonia and Hungary had compared to Norway and Sweden a higher proportion of women (resp. 39%; 38% vs. 29%; 31%), as well as patients with hypertension (resp. 79%; 72% vs. 39%; 50%), diabetes (resp. 21%; 27% vs. 14%; 19%) and peripheral artery disease (resp. 9% vs. 6%; 4%). Proportion of current smokers was highest in Norway (38%) and lowest in Sweden (27%). Rates of discharge medications were generally high. The results for in-hospital procedures and mortality are shown in table 1. Estonia had the lowest rates of dual antiplatelet treatment (78%) and statins (86%). Norway had the lowest rates of beta-blockers (80%) and angiotensin converting enzyme inhibitors/ angiotensin II receptor blockers (61%). Conclusions This cross-country comparison of four national European registries provide new insights into differences in risk factors, treatment regiments and outcomes of patients with STEMI. There are several possible reasons for the observed differences, including differences in underlying expected mortality in the populations, inclusion-criteria and coverage of the registries and variable definitions, that need to be further explored. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Estonian Research Council

Background High-risk acute pulmonary embolism (PE) is burdened by a mortality as high as 65%. VenoArterial ExtraCorporeal Membrane Oxygenation (VA-ECMO) may offer a cardiopulmonary support and a precious time window to ensure pulmonary reperfusion therapies. No definite consensus exists on the use of VA-ECMO in high-risk PE patients as only sparse observational studies are available yielding conflicting outcomes. Purpose To provide insights on the use of ECMO in acute high-risk PE pooling together all available published experiences to date. Methods Two authors (LB, AB) searched PubMed, Embase, BioMedCentral and Google Scholar, from inception to 18/09/2019. All published clinical studies investigating ECMO support in patients with high-risk acute PE were evaluated for inclusion. Results Literature search identified 384 observational studies: a total of 66 were included for 584 acute high-risk PE patients receiving ECMO support. Mean age was 46.8±16.8 years (44% female). Most patients presented with cardiac arrest (56%) or obstructive shock (42%). Diagnosis of PE was confirmed by computed tomography (CT) in 72%, performed before ECMO cannulation in 65%. Echocardiography was obtained in 89%. Right ventricle dilatation or dysfunction was found in 90% and 87%. ECMO was primarily employed as upfront treatment (63%), in the VA-ECMO configuration (94%). ECMO was equally employed in conjunction with interventional/surgical pulmonary reperfusion treatments (38%), with thrombolysis (35%) and without adjunctive procedures (40%). Mean ECMO support duration was 100.3±12.9 hours. Notably, 92% received thrombolysis before ECMO cannulation. ECMO bailout implant was mostly adopted in patients receiving thrombolysis (81% vs 19%; p=0.010), as a rescue therapy. Most common reperfusion procedures were surgical embolectomy (28%), catheter-directed thrombolysis (12%) and transcatheter embolectomy (12%). The majority of these procedures (81%) took place after ECMO cannulation. Mean total hospital stay was 17.8±11.6 days. Hospital survival rate was 54% and did not differ in upfront vs bailout ECMO (p=0.184) and between thrombolysis, interventional procedure and ECMO alone recipients (p=0.423). Neurologic death and non-fatal neurologic injury occurred both in 10%. Most patients (70%) were successfully weaned off ECMO, while 30% died on support and 7% died after ECMO removal. Acute kidney injury was the most common complication (47%). Major bleeding occurred in 19% and was fatal for 5%. Patients undergoing thrombolysis had a tendency towards higher rates of major bleeding (48% vs 23%; p=0.05). At a mean follow-up of 365.0 (IQR 202.5–365.9) days, overall survival rate was 85% in those surviving hospitalization. Conclusions In this pooled population consisting mostly of cardiac arrest/obstructive shock PE patients, ECMO strategy was associated with acceptable in-hospital survival and was frequently used in conjunction with other reperfusion treatments. Central Illustration Funding Acknowledgement Type of funding source: None

Background Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes including those generated during ischemia/reperfusion (I/R) injury in acute myocardial infarction. The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. We examined whether ALDH2*2 exacerbates I/R injury in Japanese patients with acute ST-segment elevation myocardial infarction (STEMI) utilizing Mendelian randomization. Methods and results The study subjects comprised 248 Japanese patients with STEMI (187 men and 61 women, mean age 67.1±11.5) who underwent successful primary percutaneous coronary intervention. Of these patients, 129 (52.0%) were the carriers of ALDH2*2 and 119 (48.0%) those of wild ALDH2*1/*1 on genotyping by direct application of the TaqMan polymerase chain system. There were no differences in clinical characteristics between the ALDH2*2 and ALDH2*1/*1 group except lower alcohol habit in the ALDH2*2 group. However, the peak plasma levels of creatine phosphokinase myocardial binding (CKMB), a marker of myocardial injury, were significantly higher (a median 234.0 vs 150.0 U/L, P Conclusions The peak plasma levels of CKMB were higher in STEMI patients with ALDH2*2 than in those with ALDH2*1/*1 among men but not women. These findings identified deficient ALDH2 activity to be targeted for treatment of STEMI specifically in men with ALDH2*2. Visual overview Funding Acknowledgement Type of funding source: None

Background The optimal timing for starting anticoagulation after an acute ischemic stroke related to non-valvular atrial fibrillation (AF) remains a challenge, especially in patients treated with systemic thrombolysis or mechanical thrombectomy. Purpose We aimed to assess the rates of early recurrence and major bleeding in patients with acute ischemic stroke and AF treated with thrombolytic therapy and/or thrombectomy who received oral anticoagulants for secondary prevention. Methods We combined the dataset of the RAF and the RAF-NOACs studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and AF treated with either vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Results A total of 2,159 patients were included in the RAF and RAF-NOACs trials, of which 564 patients (26%) were treated with urgent reperfusion therapy. After acute stroke, 505 (90%) patients treated with reperfusion and 1,287 out of the 1,595 (81%) patients not treated with reperfusion started oral anticoagulation. Timing of starting oral anticoagulation was similar in reperfusion-treated and untreated patients (13.5±23.3 vs 12.3±18.3 days, respectively, p=0.287). At 90 days, the composite rate of recurrence and major bleeding occurred in 37 (7%) of patients treated with reperfusion treatment and in 139 (9%) of untreated patients (p=0.127). Twenty-four (4%) reperfusion-treated patients and 82 (5%) untreated patients had early recurrence while major bleeding occurred in 13 (2%) treated and in 64 (4%) untreated patients, respectively. Seven patients in the untreated group experienced both an ischemic and hemorrhagic event. Figure 1 shows the risk of early recurrence and major bleeding over time in patients treated and not treated with reperfusion treatments. The use of NOACs was associated with a favorable rate of the primary outcome compared to VKAs (Odd ratio 0.4, 95% Confidence Interval 0.3–0.7). Conclusions Reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with AF-related acute ischemic stroke who started anticoagulant treatment. Figure 1 Funding Acknowledgement Type of funding source: None

Introduction and aim Adverse ventricular remodelling and heart failure (HF) are frequent complications of acute myocardial infarction (MI), but no reliable methods are currently available for prediction. MicroRNAs (miRNAs) can be used as biomarkers and they play a crucial role in multiple diseases onset and evolution. The aim of our study was to identify and validate a panel of serum miRNAs with differential expression in MI and test their prognostic ability to predict chronic HF. Methods Sequential approach with several models: 1) Initial selection of miRNAs by a 762 miRNA hybridization array with samples from 12 patients with acute MI and 10 age and sex-matched controls; 2) Validation of selected miRNAs in a prospective study with consecutive enrolment of patients with type 1 MI at the Cardiac ICU of a tertiary hospital; two independent cohorts were included (2013–2014 and 2017–2019) with clinical and CV imaging assessment at baseline and long-term follow-up; serum miRNAs and other biomarkers (BNP, NT-proBNP, troponin, etc) were studied; the composite HF-related outcome included HF hospitalizations and CV mortality; 30 age and sex-adjusted controls were studied for miRNAs comparison; miRNA signature study was completed with 3) in vitro model of hypoxia ±nutrient supply deprivation in H9C2 cardiomyocytes, 4) in vivo rat model of ischemia-reperfusion and 5) permanent coronary occlusion. All procedures were approved by the Ethics Committee (refs. 175/13 & 061/16), the Animals Ethics Committee (ref. 298/16) and complied with the Declaration of Helsinki. All patients provided written informed consent. Results 14 miRNAs were initially identified with highest differentiation between MI and controls. In the validation study, 311 patients with MI were enrolled, mean age 60±15, 81% male; ST elevation MI 65%, GRACE risk score 144±45, Killip class ≥II 23%, LVEF Conclusions We identified a signature of microRNAs associated with adverse ventricular remodelling and poor long-term outcome after MI, that could serve as biomarkers involved in HF progression. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III

Background The recent reperfusion therapy for ST-elevation myocardial infarction (STEMI) has made the length of hospital stay shorter without adverse events. CADILLAC risk score is reportedly one of the risk scores predicting the long-term prognosis in STEMI patients. Purpose To invenstigate the usefulness of CADILLAC risk score for predicting short-term outcomes in STEMI patients. Methods Consecutive patients admitted to our university hospital and our medical center with STEMI (excluding shock, arrest case) who underwent primary PCI between January 2012 and April 2018 (n=387) were enrolled in this study. The patients were classified into 3 groups according to the CADILLAC risk score: low risk (n=176), intermediate risk (n=87), and high risk (n=124). Data on adverse events within 30 days after hospitalization, including in-hospital death, sustained ventricular arrhythmia, recurrent myocardial infarction, heart failure requiring intravenous treatment, stroke, or clinical hemorrhage, were collected. Results In the low risk group, adverse events within 30 days were significantly less observed, compared to the intermediate and high risk groups (n=13, 7.4% vs. n=13, 14.9% vs. n=58, 46.8%, p Conclusions In STEMI patients with low CADILLAC risk score, better short-term prognosis was observed compared to the intermediate and high risk groups, and all adverse events occurred within 3 days of hospitalization, suggesting that discharge at day 4 might be safe in this study population. CADILLAC risk score may help stratify patient risk for short-term prognosis and adjust management of STEMI patients. Initial event occurrence timing Funding Acknowledgement Type of funding source: None

Introduction Exosomes have been proven to alleviate myocardial ischemia reperfusion (I/R) injury in preclinical studies. However, the laborious and low-yield production process of naturally secreted exosomes has been impeding their translation into clinical trials. Purpose We aim to develop a simple and cost-effective protocol to produce exosome mimetics, bioinspired Cell-Derived Nanovesicles (CDNs), and examine their intrinsic bioactivity in a mouse model of I/R injury. Methods CDNs were produced from human U937 monocytes using cell shearing approach and characterized by dynamic light scattering (DLS), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Lipid composition of cells and CDNs was analysed by lipidomics. I/R injury was induced by transient occlusion of left coronary artery. Data was analysed with Mann-Whitney U test. P Results We obtained 538 mg (protein content) of CDNs, or 3x109 CDNs, via cell shearing approach from 2×107 cells, approximately 15 folds of exosomes via natural secretion from the same number of cells. CDNs were 125±8 nm in diameter with negative surface charge (zeta potential −7.0±0.8) and presented as double-membranous vesicles under TEM. In vitro, CDNs showed strong antioxidant activity and could be taken up by bone marrow-derived macrophages. Following intravenous administration, as demonstrated by the IVIS Spectrum imaging system, CDNs accumulated specifically in the infarct area of the heart within 3 hours. Compared with saline treatment, CDNs reduced myocardial infarct size by 31.6% (p Conclusion We have established a cost-effective approach to produce exosome mimetics, bioinspired CDNs, which protect the heart from I/R injury via inhibition of inflammation, oxidative stress and cardiac cell apoptosis. CDNs have intrinsic cardioprotective capability in heart injury, comparable to exosomes. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National University Health System.

Introduction Owing to the ageing of the population, nonagenarian patients are increasingly present in catheterization laboratories, part of them with ST-segment elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) is the recommended reperfusion therapy in patients with STEMI, provided it can be performed promptly. However, elderly patients are usually excluded from clinical trials and few data are available about nonagenarians referred for primary PCI. Purpose The aim of the present study was to evaluate clinical characteristics and in-hospital outcomes of nonagenarians STEMI patients undergoing primary PCI. Methods We retrospectively analyzed clinical, angiographic and in-hospital outcomes of death, re-infarction and stroke of primary PCI in nonagenarian STEMI patients, included in the Brazilian PCI Registry (CENIC) between June 2006 and March 2016. Predictors of in-hospital mortality of this population were determined through multivariate analysis. Results Over a period of 10 years, 847 nonagenarians were enrolled in the CENIC Registry, and 252 presented with STEMI and underwent a primary PCI. The population was predominantly female (55.2%), with a median age of 92 years (interquartile range 4 years, maximum of 105 years) and 63.9% in Killip class I at admission. Median door-to-balloon time was 90±60 minutes. Double or triple-vessel disease was found in 63%. It was used 1.3 stent per patient, 8.9% drug-eluting stents. The femoral access route was preferred in 82.1% of patients and glycoprotein IIb/IIIa inhibitors was given to 9.9%. In-hospital mortality in the period was 10.7% and re-infarction occurred in 0.5%. No cases of stroke have been reported. The only predictor of hospital mortality was Killip class (OR 7.1, 95% CI 2.7–18.5, p Conclusion In a real-world setting, primary PCI in nonagenarian STEMI patients can be performed with good clinical outcomes and acceptable in-hospital mortality rate and must be recommended even in oldest-old age patients. Killip class was the only predictor of in-hospital mortality in this population. Funding Acknowledgement Type of funding source: None

Background It was previously demonstrated that in patients with ST segment elevation myocardial infarction (STEMI) high-sensitive troponin-T (Hs-cTnT) makes two peaks. However, the clinical significance of the second peak (early vs late) in patients undergoing successful primary percutaneous intervention (pPCI) is not known. We investigated the role of early second peak on clinical outcomes. Methods Patients who underwent successful pPCI were included. Baseline characteristics, angiographic variables and kinetics of Hs-cTnT levels following pPCI were recorded. Second peak of Hs-cTnT was defined as re-elevation of troponin levels above plateau levels. The second peak of Hs-cTnT is defined as early second peak, if re-elevation is detected earlier than 72 hours after the diagnosis and late second peak, when re-elevation is detected later than 72 hours. Results We included 250 patients divided into two groups; patients with early second peak as group 1 (n=118) and rest of the patients as group 2 (n=132). Baseline characteristics and comorbidities were similar. Peak level of Hs-cTnT, Hs-CRP and pro-BNP levels were significantly lower in group 1 patients. Left ventricular ejection fraction was higher in group 1 patients (47.48±7.7 vs 43.80±9.3, p-value: 0.001). There was no significant difference with respect to new-onset heart failure (24% vs %28, p: 0.503) between groups however cardiac mortality was significantly lower in group 1 patients (%2 vs %11, p: 0.007). Conclusion The early second peak of Hs-cTnT in patients with STEMI is associated with successful reperfusion and predictors of better clinical outcome. Moreover, early second peak of Hs-cTnT is associated with decreased cardiac mortality and has a potential to be used as a marker of good prognosis. Funding Acknowledgement Type of funding source: None

Introduction The outcome of acute ST-elevation myocardial infarction depends, to a large extent, on the size of the infarct. Myocardial damage due to infarction involves several pathogenic mechanisms among which excessive generation of reactive oxygen species and an exacerbated inflammatory reaction play a critical role. Spirulina is a dietary supplement made from blue-green algae (Arthrospira platensis) used to manage weight loss and metabolic syndrome disorders. In addition, Spirulina has experimentally shown to exert anti-oxidant and anti-inflammatory properties because its composition rich in antioxidants, polyunsaturated fatty acids, essential amino-acids, and minerals. Purpose The purpose of the present study was to investigate whether dietary supplementation with Spirulina may serve as a cardioprotective agent by attenuating cardiac damage and ventricular dysfunction due to myocardial infarction in a highly translatable animal model. Methods Pigs (n=10) were fed a normocholesterolemic diet supplemented with Spirulina (1 gr/animal/bid; n=5) or placebo (n=5) for 10 days and then they were subjected to myocardial infarction by means of 1.5h balloon occlusion of the mid left anterior descending coronary artery. Thereafter animals were reperfused for 2.5h and then sacrificed. Infarct size was assessed by TTC staining and ischemic and non-ischemic myocardial tissue was obtained for molecular analysis of cardioprotective kinases, anti-apoptotic- and anti-inflammatory- related markers. Biochemical analyses (lipid levels, kidney and liver parameters) and weight gain were monitored throughout the study. Results Supplementation with Spirulina led to an absolute significant reduction in infarct size of 10±1% of the left ventricle (LV) as compared to control animals (p Conclusion Supplementation with Spirulina, beyond its proven benefits in weight loss and lipid profile, exerts cardioprotection by inducing myocardial survival kinases, and triggering cytoprotective and anti-inflammatory mechanisms, thereby limiting cardiac damage and improving ventricular contractility post-MI. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministerio de Ciencia Innovacion y Universidades / Instituto de Salud Carlos III

Background Adverse left ventricular (LV) remodelling is associated with development of heart failure and poor outcomes in patients with acute myocardial infarction (AMI). Understanding the immunomodulatory mechanisms of LV remodelling is an essential step for the development of novel therapies. Interferon-γ-inducible protein-10 (IP-10)/CXCL10 is a chemokine involved in the recruitment of activated T cells into sites of tissue inflammation. Although IP-10 was reported to reduce adverse LV remodeling in a preclinical myocardial infarction model, its role in LV remodeling in humans with AMI remains unknown. Purpose To determine the clinical predictive value of serum IP-10 in LV remodeling in patients with ST-segment elevation myocardial infarction (STEMI). Methods This is a substudy of the double-blind, randomised controlled trial “Evaluating the effectiveness of intravenous ciclosporin on reducing reperfusion injury in patients undergoing primary percutaneous coronary intervention” (CAPRI; ClinicalTrials.gov registry number NCT02390674), which enrolled 52 acute STEMI patients. LV remodeling was assessed by cardiovascular magnetic resonance (CMR) imaging and was defined as the 12-week vs. the 3-day post-myocardial infarction change of the left ventricular ejection fraction (ΔLVEF), LV end-diastolic volume (ΔEDV) or LV end-systolic volume (ΔESV). Serum IP-10 was measured before and 5min, 15min, 30min, 90min and 24h after reperfusion by ELISA. Linear regression analysis was used to determine the independent association of IP-10 with the endpoints of the study. Results Serum IP-10 concentration peaked at 30min after reperfusion followed by a 2-fold decrease at the 24h post reperfusion compared to pre-reperfusion levels (P Conclusions Increased serum IP-10 levels early after reperfusion are associated with reverse LV remodeling in patients with STEMI undergoing primary PCI. The clinical application of IP-10 as a novel biomarker of LV remodeling post-AMI should be further explored and validated. Funding Acknowledgement Type of funding source: None

Background Coronary artery ectasia (CAE), is only found in about 1% of acute myocardial infarction (AMI), but represents a clinical challenge in the setting of percutaneous coronary intervention (PCI), considering 1) culprit lesion or not, 2) a solely CAE or mixt 3) number, localization and size of CAE, 4) etiology and 5) therapeutic strategies. Only few studies from small cohorts have focused on infarct-related arteries. We aim to assess the impact of CAE as culprit artery on management strategy. Methods From 2010 to 2019, this study prospectively analyzed the characteristics, and management of 70 consecutive admitted for an AMI and with CAE at coronary angiography. Patients with ectatic infarcted-related artery (ERIA) were compared with patients without ectasia localized on infarcted-related (No ERIA). Results Among the 70 patients included, most had ERIA 47 (67%). ERIA patients had more frequently diabetes than patients without ERIA (32 vs 4%, p=0.01). The rate of other CV risk factors, and chronic medications, including antiplatelet agents and anticoagulants,.were similar for the 2 groups. Moreover, no difference was observed between the 2 groups for clinical parameters and biological data. Whatever the group, the ectatic artery is mainly located on the right coronary artery (RCA) (73%), of which most were ERIA (77%). ERIA group had less frequently anterior wall location STEMI (18 vs 65%, p= PCI data and hospital mortality are shown in Table. Conclusion CAE management is strongly dependent on the presence of CAE on IRA. Although rare, the optimal treatment strategy of patients with AMI and CAE remains to be elucidated. The place of intravascular ultrasound imaging needs to be investigated. Funding Acknowledgement Type of funding source: None

Introduction Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect occurring in a significant proportion of patients. Irreversible mitochondrial damage is a central mechanism of AIC. Despite many efforts, there is a lack of therapies able to prevent AIC. Remote ischemic preconditioning (RIPC) could be a promising therapy to prevent AIC due to the scheduled application of chemotherapy in cancer patients. Purpose To evaluate the cardioprotective efficacy of RIPC in large animal model of AIC. Methods Large-White pigs (n=20) underwent a validated protocol of AIC consisting on five intracoronary doxorubicin injections (0.45 mg/kg), on weeks 0, 2, 4, 6, 8 of the study. Pigs were randomized before the initiation of the study to remote ischemic pre-conditioning (RIPC, 3 cycles of 5 min lower limb ischemia followed by 5 min reperfusion) or sham procedure immediately before doxorubicin injections. An additional group of 10 pigs without any exposure to doxorubicin was carried out as controls. Pigs underwent a comprehensive serial cardiac magnetic resonance (CMR) exam baseline, and on weeks 6, 8, 12, and 16. After 16-week CMR, pigs were sacrificed and tissue samples collected. A second group of 10 pigs (randomized 1:1 for RIPC) underwent the same protocol but were sacrificed 2 weeks after the third doxorubicin dose for early evaluation of tissue changes. Primary endpoint of the study was CMR-based left ventricular ejection fraction on week 16. Results Until week 6 (time of fourth doxorubicin injection), LVEF remained unchanged in both groups. From there on, a progressive decline in LVEF was observed. LVEF depression trajectory was blunted in RIPC animals. Compared to controls, pigs undergoing RIPC before each doxorubicin dose had a significantly higher LVEF at week 16: median (IQR) 45% (27–50%) vs 33% (19–47%) in RIPC and controls respectively, p=0.04. Improvement in LVEF was mainly due to a more preserved contractile function, as evidence by smaller LVESV, and better regional contractile function. After 3 doxorubicin doses, a time where global (LVEF) and regional contractile function was still unchanged, transmission electron microscopy (TEM) showed fragmented mitochondria with remodeled cristae only in control pigs. At the end of the 16 weeks, TEM evaluation in control pigs (as compared to RIPC pigs) showed overt cardiomyocyte's mitochondrial fragmentation with overt structural derangement. At this time, RIPC pigs had significantly less interstitial fibrosis on histology. Conclusions In a translatable large animal model of AIC, RIPC applied immediately before each doxorubicin cycle resulted in a preservation of cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented the deleterious effects of doxorubicin on mitochondria since early stages of AIC. RIPC is a promising intervention to be tested in clinical trials to prevent cardiotoxicity. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovaciόn and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505)

Introduction Nanomedicine offers great potential for treatment of cardiovascular disease. We tested whether intramyocardial (IM) injection of pro-angiogenic hepatocyte growth factor (HGF) and anti-apoptotic, pro-myogenic insulin-like growth factor 1 (IGF-1) encapsulated in Alginate-Sulfate nanoparticles (AlgS-NP) improves left ventricular (LV) functional recovery in a porcine ischemia-reperfusion (I/R) model. Methods Myocardial infarction (MI) was induced by 75min balloon occlusion of the mid-LAD followed by reperfusion. After 1w, pigs (n=12) with marked LV dysfunction (EF Results At 1w after MI, LV ejection frqction (LVEF) was 37±5% (range 27–45%) and infarct size (IS)/LV mass 24±6% (range 19–38%). Myocardial retention of AlgS-NP was comparable between 2 groups (maximal systemic leakage after IM injection: 9% CON vs 20% GF, P=0.25). After 8 w, IS/LV mass decreased by one third in GF-treated pigs compared with 14% in CON (P=0.03, Fig. A) and was associated with a trend towards improvement in CFR (P=0.05, Fig. B). LVEF significantly increased in GF-treated pigs (6±2% vs. −1±1%, P=0.02, Fig. C), which was attributable to a greater reduction in end-systolic volume. The improvement in LVEF was also consistent with significant reduction of fibrosis (P=0.01, Fig. D) in the peri-infarct zone (PI). Conclusions Intramyocardial injection of AlgS-nanoparticle-encapsulated HGF and IGF-1 to the ischemic myocardium significantly improves LV repair, and offers the prospect of innovative treatment for patients with refractory ischemic heart disease. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): EuroNanoMed, Horizon 2020

Background Since the inception of clinical guidelines on the management of patients with acute coronary syndrome (ACS), betablocker therapy has been included as a class I recommendation. However, most studies evaluating betablockers in ACS were conducted in the pre-reperfusion era. Currently, the great majority of patients undergo reperfusion and secondary prevention therapy has evolved; the impact of treatment with a betablocker in these patients may be different. Purpose We conducted a systematic review and meta-analysis to evaluate the impact of betablockers on mortality in patients after an ACS in the reperfusion era. Methods We searched MEDLINE, EMBASE, and Cochrane Central Registry of Controlled Trials for RCTs from inception to September 2019. We included randomized controlled trials comparing betablockers to no betablockers in adult patients presenting with an ACS. Independently and in duplicate, we screened titles and abstracts, reviewed the full-text report of potentially eligible studies and extracted data. Two reviewers also evaluated the risk of bias in duplicate. Disagreements were addressed by consensus. We considered trials to be conducted in the reperfusion era if reperfusion was attempted in more than 50% of patients, either with thrombolytics or primary angioplasty. Our primary outcome of interest was all-cause mortality. Secondary outcomes included hospitalization for heart failure, nonfatal myocardial infarction, stroke and cardiogenic shock. We pooled trial outcomes using a fixed effects model. The study protocol is registered with PROSPERO (CRD42019143158). Results After the initial screening of 10,969 references and full-text review of 176 articles, nine RCTs comprising a total of 49,639 patients with ACS were eligible for the final analysis. Predominantly, these patients presented with ST elevation myocardial infarction. Treatment with a betablocker did not improve all-cause mortality at 30 days (risk ratio (RR) 0.98 [95% CI 0.92–1.04], I2=44%), or at longest follow up (up to three years) with RR 0.97 ([95% CI 0.91–1.03], I2=0%). Betablocker therapy was associated with an increased risk of HF hospitalization (RR 1.10 [95% CI 1.05–1.15], I2=52%) and cardiogenic shock during index hospitalization (RR 1.29, [95% CI 1.18–1.40], I2=0%). However, betablocker therapy reduced the risk of nonfatal myocardial infarction (RR 0.72 [95% CI 0.63–0.83], I2=0%); it did not impact the risk of stroke (RR 1.13 [95% CI 0.95–1.35], I2=0%). Conclusion In the reperfusion era, betablocker therapy after an ACS does not appear to improve short or long-term survival. Although betablocker therapy was associated with a reduction in nonfatal myocardial infarction, it increased the risk of heart failure hospitalization and cardiogenic shock. In light of these findings, clinical guidelines should reconsider the strength of their recommendation for betablocker use in the ACS population until further contemporary evidence is available. Funding Acknowledgement Type of funding source: None

Background Hyperglycaemia is a common finding in diabetic and non-diabetic patients presenting with ACS, and is a powerful predictor of prognosis and mortality. The role of hyperglycaemia in ischemia-reperfusion injury (IRI) is not fully understood, and whether the Sodium Glucose co-Transporter 1 (SGLT1) plays a role in infarct augmentation, before and/or after reperfusion, remains to be elucidated. However, diabetes clinical trials have shown SGLT inhibition improves cardiovascular outcomes, yet the mechanism is not fully understood. Purpose (1) Characterise the expression of SGLT1 in the myocardium, (2) determine the role of high glucose during IRI, (3) whether SGLT1 is involved in a glucotoxicity injury during IRI, and (4) whether inhibiting SGLT1 with an SGLT inhibitor may reduce infarct size. Methods RT-PCR and in-situ hybridization (RNAScope) techniques were used to detect SGLT1 mRNA expression in Sprague-Dawley whole myocardium and isolated primary cardiomyocytes. An Ex-vivo Langendorff ischemia-reperfusion perfusion model was used to study the effect of high glucose (22mmol) on the myocardium at reperfusion compared to normoglycaemia (11mmol). The mixed SGLT1&2 inhibitor, Phlorizin was introduced following ischaemia, at reperfusion and its effect on infarct size measured using triphenyltetrazolium chloride (TTC) staining. Results RT-PCR found SGLT1 mRNA is expressed in whole myocardium and in individual cardiac chambers. SGLT1 expression was not detected in isolated cardiomyocyte but it is detected in the non-cardiomyocyte population. Cardiomyocytes were found to express mRNA SGLT1 if incubated overnight. RNAscope detected SGLT1 mRNA within intact myocardium: not in the cardiomyocyte, but rather in a perivascular distribution. Importantly, hyperglycaemia (22mmol) at reperfusion increased infarct size (51.80±3.52% vs. 40.80±2.89%; p-value: 0.026) compared to normoglycaemia, and the mixed SGLT inhibitor, Phlorizin, significantly attenuated infarct size (from 64.7±4.2%to 36.6±5.8%; p-value Conclusion We have shown that SGLT1 is present in the myocardium, but not expressed in cardiomyocytes. The cell type is yet to be determined, but the distribution of SGLT1 is perivascular. Hyperglycaemia appears augment myocardial infarction and inhibition of SGLT1&2 attenuates this increase. We suspect SGLT1 may plays a role in exacerbating the injurious effect of glucotoxicity during ischemia-reperfusion. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Background/Introduction ST segment elevation myocardial infarction (STEMI) is a frequent cause of Cardiac Arrest (CA), and early percutaneous coronary intervention is associated with increased hospital survival in these patients. Despite constant improvements in out-of-hospital CA management, survival remains low. Purpose Our aim was to assess pre-admission CA incidence, predictors and related outcomes in patients admitted with STEMI. Methods We prospectively included 1083 patients admitted with STEMI in a tertiary university hospital in southern Brazil between March 2011 and October 2019. All patients were submitted to emergency coronary angiography. Baseline characteristics, details of the procedure, reperfusion strategies, and in-hospital outcomes were evaluated. Results Mean age was 60.8 years (± 12), 66.2% were male, 62% had hypertension and 25.3% had diabetes. Pre-admission CA was present in 104 (9.8%) patients. Patients with CA had more frequently previous myocardial infarction, temporary pacemaker, smoking and Killip 3 or 4 on admission, and shorter pain–to-door time than patients without CA. In addition, CA patients had a higher incidence of periprocedural CA, cardiogenic shock and periprocedural and in-hospital mortality. In multivariate analysis, age (RR= 0.96, p=0.001), anterior MI (RR=1.67, p=0.04) smoking (RR=0.57, p=0.04), previous ASA use (RR=0.40, p=0.02), Killip 3 or 4 (RR=14.71, p Conclusion In this cohort of consecutive patients admitted with STEMI, pre-admission CA incidence was greater than seen in literature. Cardiogenic shock and in-hospital mortality were more common in patients admitted with CA, which may in part explain our higher rate of overall in-hospital mortality. Non shockable rhythm, increased ROSC and cardiogenic shock were independent predictors of mortality among patients admitted with CA. Understanding these characteristics may help taking measures to lower mortality rates. Funding Acknowledgement Type of funding source: None

Introduction Acetylcholinesterase inhibition by donepezil has been shown to improve long-term survival in permanent myocardial infarction (MI)-induced chronic heart failure rats. This study examined whether donepezil is applicable to the treatment of obesity-induced hypertension with reperfused MI (RMI). Methods Four-week-old SD rats were fed a high-fat diet (57% kcal as fat) for 15 weeks. We implanted a blood pressure (BP) telemetry into the animals (8-week-old) for monitoring artery pressure. After a 1-week recovery, RMI was created by occluding the left coronary artery (30min) followed by reperfusion. Surviving animals were randomly assigned to untreated (UT, n=16) or donepezil treated (DT, n=16, 3 mg/kg/day) group. After a 10-week treatment, the effects of donepezil were evaluated by hemodynamics, blood biomarkers, immunohistochemistry, and morphology. Results The high-fat diet caused obesity and hypertension (9-week-old: systolic BP = 134±4 mmHg; diastolic BP = 92±2 mmHg) in the normal rats. Compared with UT, DT significantly decreased the heart rate (296±5 vs. 318±8 bpm, P Conclusions Donepezil treatment significantly suppressed the progression of cardiovascular remodeling and dysfunction following RMI in obesity-induced hypertensive rats, suggesting that donepezil may be used as a potential candidate for post-RMI therapy in obesity-induced hypertensive patients. Funding Acknowledgement Type of funding source: None

Background Long-term reports on reperfusion therapy for acute ST-segment elevation myocardial infarction (STEMI) in developing countries are scarce. Purpose We reported changes in acute reperfusion therapy for STEMI that have been observed over time in an academic tertiary care percutaneous coronary intervention (PCI) centre that hosting a STEMI network in the large metropolitan area of Jakarta, Indonesia since 2010 and covering around 11 million inhabitants. Methods A retrospective analysis was performed in 6336 patients with STEMI who admitted to the emergency department of a PCI centre in 2008 (before STEMI network introduction), and during 2011 to 2018. Results Among STEMI patients admitted during 2011–2018 (mean age: 56±10 years, 86% male), 57.6% had anterior wall myocardial infarction, and 71.3% presented with Killip classification I. Compared with the period 2011–2014 (N=2766), patients who were admitted in the period 2015–2018 (N=3250) were receiving more primary percutaneous coronary intervention (PCI) (61.6% vs. 44.2%, P Conclusion The data indicate that the introduction of a STEMI network resulted in more patients receiving timely primary PCI and lower early mortality rates in recent years. Funding Acknowledgement Type of funding source: None

Introduction Total ischemic time (TIT), the time from symptom onset to therapeutic reperfusion of infarcted myocardium is a key factor in the treatment of patients with ST-segment elevation myocardial infarction (STEMI). The identification of the predictive factors of a prolonged TIT will allow design specific strategies to optimize this time and improve the quality of care of these patients. Our objective was to evaluate independent factors predicting prolonged TIT. Methods We performed a prospective observational study, with consecutive inclusion of all patients presenting within 24 hours of symptom onset of STEMI (n=546), transferred to our center for primary percutaneous coronary intervention (pPCI). Results The median TIT was 190 (137–281) minutes. No significant differences were found according to the year of study. In the univariate analysis, age showed a slight trend (p=0.05); for each year that is increased, the TTI increases 1.3 minutes. Women had higher TII than men [219 (145–332) vs. 187 (133–270) minutes; p=0.02]. No statistically significant differences were found in relation to the presence of cardiovascular risk factors. Patients treated during non-working hours had shorter TIT than those treated during working hours [179 (130–252) vs. 202 (142–307) minutes; p=0.03]. The distance to a 24h-PCI hospital was an independent predictive factor. Those patients whose first medical contact (FMC) was in a non-PCI-capable hospital or in a clinic showed the highest TIT [226 (147–336) and 205 (146–304) minutes, respectively; p90 km) were independent predictive factors of a TIT >180 minutes. An initial non-diagnostic or misinterpreted ECG sextuples the risk of a prolonged TIT. Conclusions In our area, the total ischemic time is determined by a non-diagnostic or misinterpreted EKG, the first medical contact and the distance to a 24h-PCI hospital. Funding Acknowledgement Type of funding source: None

Background Sarcopenia is a pathophysiological malfunction induced by skeletal muscle atrophy, and several studies reported an association between sarcopenia-induced cardiac cachexia and poor prognosis in heart disease. Since only a few established animal models are recently available, the underlying mechanism of disturbed cardiac repair accompanied with sarcopenia remains poorly understood. Purpose We hypothesized that specific microRNAs in sarcopenia-derived exosomes play crucial roles in disturbed cardiac repair with sarcopenia, and these microRNAs directly exacerbate cardiomyocyte injury following cardiac ischemia and reperfusion. Methods We developed a novel sarcopenia-induced cardiac repair disturbance mouse model that is induced by tail suspension (TS) 7 days after a 45-min coronary occlusion of cardiac ischemia and reperfusion (I/R). The reduction of the left ventricular ejection fraction (LVEF) after I/R was compared in mice with TS [I/R-TS(+), n=14] and without [I/R-TS(−), n=12] by echocardiography. To investigate the exosomal mechanism of cardiac repair disturbance, a comprehensive analysis of extracted exosomal microRNAs from mice serum was performed in the 2 groups at day 8. Then, we investigated the impact of the identified candidate microRNA in neonatal rat cardiomyocytes (NRVMs). After 4 days in primary culture, candidate microRNA was transfected into NRVMs under hypoxic culture conditions. TUNEL analysis and quantitative PCR analysis of apoptosis-related genes were performed on the NRVMs. Results At day 8 after I/R, the LVEF of I/R-TS(+) was not significantly ameliorated compared to that of I/R-TS(−) (ΔLVEF; 1.59±6.92 vs. 8.04±7.71% p=0.034). Four candidate microRNAs obtained from I/R mice serum were identified in the microRNA array analysis. The re-analysis of these candidate micro-RNAs using all I/R mice demonstrated that the level of mir-16-5p in I/R-TS(+) was raised by approximately nine-fold than that in I/R-TS(−) (9.67±13.35 vs. 0.99±1.41, p Conclusion Myocardial I/R injury in sarcopenia ended in cardiac repair disturbance accompanying with the enhanced expression of exosomal-mir-16-5p. A pro-apoptotic effect of mir-16-5p may exacerbate myocardial I/R injury and thus can be a novel therapeutic target for cardiac repair disturbance in sarcopenia. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver. Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

Background Cardiogenic shock (CS) is an ominous complication of ST elevation myocardial infarction (STEMI). However, the widespread use of reperfusion therapies and invasive management could have reduced the prevalence of CS and improved the prognosis of these patients in the last decades. Purpose The aim is to analyze the changes over last three decades in the prevalence, management and acute phase prognosis and 1-year mortality of STEMI patients complicated with CS. Method Between February 1989 and December 2017, 7,589 STEMI patients were consecutively admitted in the Coronary Care Unit of a University Hospital and were included in a prospective registry. Depending on the year of admission, patients were classified in five groups: 1989–1994: n=1,337, period 1; 1995–1999: n=960, period 2; 2000–2004: n=1,059, period 3; 2005–2009: n=1,535, period 4 and 2010–2015: n=2,698, period 5). We analyze the trend in prevalence of CS, management and 28-day and 1-year mortality over these five periods. Results The global prevalence of CS was 6.1% (466 patients), mean age was 67.7 (SD 11.7) years and 68.7% were men. Prevalence of CS in STEMI decreased from period 1 to 5 (7.3%, 6.4%, 5.5%, 5.8%, 6.0%, p Kaplan-Meier curves, 1-year mortality Conclusions Cardiogenic shock development in STEMI patients has been reduced from 7.3% to 6.1% in the last three decades. The whole improvement in management of these patients achieves a 37% of reduction in 28-day case fatality and 1-year all-cause mortality. Despite this improvement, acute phase (28-day) case fatality of STEMI complicated with CS remains over 57% in the primary angioplasty era.

Background Short time from symptom onset until reperfusion is imperative in ST-elevation myocardial infarction (STEMI). System delay has been successfully shortened but patients delay has had less favorable development. The aim of this study was to find out clinical, contextual, behavioral and cognitive factors associated with decision time in STEMI. Method SymTime was a multicenter observational cross-sectional self-reported survey study performed at five Swedish hospitals representing geographic diversity. Early and late action was defined as decision to seek care 90 min, respectively. Results 532 patients were included. Among those 19.5% called Emergency Medical Services (EMS) as first medical contact (FMC) within 20 min, whereas 10.7% acted within 20 min, but did not call EMS as FMC. Twenty-eight % called EMS as FMC, but delayed >20 min and 41.7% neither acted promptly, nor called EMS as FMC. Predictors associated with decision time OR 95% CI Factors associated with decision time 90 min Female gender 1.67 1.06–2.62 Diaphoresis 0.67 0.46–0.998 Nausea 0.60 0.36–0.998 Stomach pain 0.46 0.23–0.91 Believing the symptoms originated from the heart 0.46 0.32–0.68 Getting STEMI off hours 1.68 1.16–2.14 Low educational level 0.58 0.40–0.86 Bystanders calling or recommending EMS contact 0.45 0.30–0.67 Variable significant at the p 0.05 presented. Conclusion Surprisingly, no specific symptom or severity of symptom were associated with early action, neither age, nor gender. Instead correct interpretation of symptoms and bystanders assisting were factors associated with early action. Frightening symptoms such as diaphoresis was negatively associated, whereas female gender and getting MI off hours were positively associated with late action.