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Background Right heart dysfunction (RHD) parameters, such as right ventricular to pulmonary artery uncoupling or significant tricuspid regurgitation (TR) are increasingly important in heart failure (HF), especially in patients with preserved ejection fraction. In this study, we aimed to evaluate the association of advanced RHD with the risk of recurrent admissions across the spectrum of left ventricular ejection fraction (LVEF). Methods We included 3,383 consecutive patients discharged for acute HF (AHF). Of them, in 1,435 (42.4%) pulmonary artery systolic pressure (PASP) could not be accurately measured, leaving a final sample size of 1,948 patients. Advanced RHD was defined as the combination of a ratio of tricuspid annular plane systolic excursion (TAPSE)/PASP Results At a median follow up of 2.2 years (IQR=0.63–4.71), 3,782 readmissions were registered in 1,296 patients (66.5%). Patients with advanced RHD showed higher rates of readmissions, but only if LVEF≥40% (p Conclusion Following an admission for AHF, advanced RHD was strongly associated with a higher risk of recurrent CV and HF admissions, but only in patients with LVEF≥40%. Funding Acknowledgement Type of funding sources: None.

Background The impact of sex in patients with chronic coronary syndrome (CCS) has been widely reported, but little is known about the influence of sex on the risk of new-onset HF in patients with CCS. Objectives We aimed to examine sex-related differences and new-onset heart failure (HF) risk in patients with known or suspected CCS undergoing vasodilator stress cardiac magnetic resonance (CMR). Methods We prospectively evaluated 5,899 consecutive HF-free patients submitted to stress CMR for known or suspected CCS. Ischemic burden (number of segments with stress-induced perfusion deficit) and left ventricular ejection fraction (LVEF) were assessed by CMR. The association between sex and new-onset HF (including outpatient diagnosis or acute HF hospitalization) was evaluated using a Cox proportional-hazards regression model adjusted for competing events (death, myocardial infarction, and non-CMR-related revascularization). Results A total of 2,289 (38.8%) patients were women, and 539 (9.1%) underwent CMR-related revascularization. During a median follow-up of 4.5 years, 610 (10.3%) patients died, 191 (3.2%) suffered a myocardial infarction, 420 (7.1%) underwent CMR-non-related revascularization, and 314 (5.3%) developed new-onset HF. Unadjusted new-onset HF rates were higher in women than in men (1.25 vs 0.83 per 100 person/years, p=0.002) (Figure 1). After comprehensive multivariate adjustment, women showed an increased risk of new-onset HF (HR=1.61, 95% CI: 1.21–2.13, p=0.001). Compared with men, the risk of new-onset HF was higher in women with LVEF >53%. Conclusions Compared with men, women with CCS are at a higher risk of new-onset HF. Further studies are needed to unravel the mechanisms behind these sex-related differences. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) Figure 1

Funding Acknowledgements Type of funding sources: None. Introduction Acute pulmonary embolism (PE) is the third cause of cardiovascular mortality, right after acute myocardial infarction and stroke. Systemic thrombolytic therapy (SLT) restores pulmonary perfusion earlier than low molecular-weight heparin, but with a significantly higher risk of major bleeding. Currently, in our area there is a lack of standardized protocols for the management of patients in which SLT is contraindicated. Objective The purpose of our study was to evaluate the safety and efficacy of percutaneous catheter-directed treatment (PCT) for high-intermediate risk PE (HIRPE) patients with hemodynamic deterioration on anticoagulation treatment. Methods We consecutively included all patients with HIRPE patients who underwent PCT in our center. Before and after PCT clinical, echocardiographic and hemodynamic variables were collected, as well as events (major or minor bleeding, death) during follow-up. Results From February 2018 to February 2020, 20 patients with HIRPE underwent PCT. The mean age of our cohort was 62 (52 - 73), and 46.6% were women. The indication for PCT was absolute contraindication for SLT (9 patients, 45%), followed by high bleeding risk (8 patients, 40%) and failure of SLT. Vascular access was mainly performed through femoral vein (12 patients, 60%) followed by a peripheral vein of the superior limb (8 patients, 40%). During pulmonary angiography, lobar arteries occlusion was observed in 60% of the cases, with involvement of main pulmonary arteries in 40% of the cases. Local thrombolysis with Alteplase was performed in 17 cases (85%), and in 8 cases it was decided to carry-out a thrombus fragmentation-aspiration strategy. We observed and early improvement of hemodynamic parameters after PCT, with a significant reduction of mean pulmonary artery pressure before and after PCT (40 +/- 13 mmHg vs. 25 +/- 12 mmHg, p < 0.001, figure 1), as well as an improvement in systolic blood pressure (102 +/- 13 mmHg vs. 129 +/- 14, p < 0.001) and the partial pressure of oxygen (51 +/- 3 vs. 67 +/- 2, p = 0.002). We also observed a significant decrease in NT-proBNP values at admission and 48 hours after PCT (4791 +/- 1077 pg/mL vs. 2311 +/- 680 pg/mL, p = 0.002, figure 2), as well as an improvement in echocardiographic right ventricular function parameters evaluated at admission and 72 hours after PCT, such as TAPSE (15 +/- 2 mm vs 22 +/- 3 mm, p = 0.001) or right ventricle basal diameter (51 +/- 4 mm vs. 41 +/- 2 mm, p = 0.001). During a median follow-up of 7 months (4 - 12 months) one patient died of non-cardiac cause and none of them had a major or minor bleeding event. Conclusion PCT in patients with HIRPE with hemodynamic deterioration on anticoagulation is a simple and effective procedure with an immediate reduction of mean pulmonary pressure and an early improvement of right ventricle-related biochemical, hemodynamic and echocardiographic parameters. Abstract Figure 1: mPAP after and before PCT.

Objectives High-sensitivity troponin is a biomarker of myocardial damage and is associated with a greater risk of mortality and disease progression in patients with acute heart failure (AHF). However, its relationship with the risk of future readmissions is less known. The aim of this study was to assess the association between ultrasensitive troponin T (TnT-us) values in patients with AHF and the risk of recurrent readmissions in the follow-up. Methods We prospectively included a cohort of 621 consecutive patients with AHF, excluding those patients with acute coronary syndrome. We measured the TnT-us levels obtained during the first medical contact in the emergency department. The risk of cumulative readmissions was assessed using negative binomial regression. Results The mean age of the participants was 73.6 ± 10.8 years, 54.6% were men, and 52% had a left ventricular systolic function ≥50%. The median TnT-us level was 35.5 pg/mL (interquartile range [IQR], 22–67). After a median follow-up of 1.2 years (IQR, 0.4–2.4), a total of 153 deaths (24.6%) were recorded, as well as 689 readmissions for all causes in 303 patients (48.8%) and 286 readmissions for HF in 163 patients (26.3%). In the multivariate analysis, the high TnT-us values were associated with an increased risk of readmission, both for all causes and for HF (incidence rate ratio [IRR], 1.16; 95% CI, 1.02–1.36; p = .029 and IRR, 1.23; 95% CI, 1.04–1.46; p = .018, respectively). Conclusions For patients with AHF, the increase in TnT-us levels was independently associated with a risk of recurrent readmissions during the follow-up.

Background The Charlson's is the most used comorbidity index. It comprises 19 comorbidities, some of which are infrequent in elderly patients with acute coronary syndrome (ACS), while some others are manifestations of cardiac disease rather than comorbidities. Purpose Our goal was to simplify comorbidity assessment in elderly non-ST-segment elevation ACS patients. Methods The study group consisted of 1 training (n=920, 76±7 years) and 1 testing (n=532; 84±4 years) cohorts. The end-point was all-cause mortality at 1-year follow-up. Comorbidities were assessed selecting those medical disorders other than cardiac disease that were independently associated with mortality by multivariable analysis. Results A total of 130 (14%) patients died in the training cohort. Six comorbidities were predictive: renal failure, anemia, diabetes, peripheral artery disease, cerebrovascular disease and chronic lung disease. The increase in the number of comorbidities yielded a gradient of risk on top of well-known clinical predictors: ≥3 comorbidities (27% mortality, HR=1.90, 95% CI 1.20–3.03, p=0.006); 2 comorbidities (16% mortality, HR=1.29, 95% CI 0.81–2.04, p=0.30); and 0–1 comorbidities (7.6% mortality, reference category). The discrimination accuracy (C-statistic= 0.80) and calibration (Hosmer-Lemeshow test, p=0.20) of the predictive model using the 6 comorbidities was comparable to the predictive model using the Charlson index (C-statistic=0.80; Hosmer-Lemeshow test, p=0.70). Similar results were reproduced in the testing cohort (≥3 comorbidities: 24% mortality, HR=2.37, 95% CI 1.25–4.49, p=0.008; 2 comorbidities: 14% mortality, HR=1.59, 95% CI 0.82–3.07, p=0.20; 0–1 comorbidities: 7.5% reference category). Kaplan-Meyer curves for mortality Conclusion A simplified comorbidity assessment comprising 6 comorbidities provides useful risk stratification in elderly patients with ACS Acknowledgement/Funding This work was supported by grants from Spain's Ministry of Economy and Competitiveness through the Carlos III Health Institute

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma LDL. Beyond lipid control, recent findings suggest a deleterious effect of this protein in the pathogenesis of post-myocardial infarction left ventricle remodeling and heart failure-related complications. The aim of this work was to assess the relationship between circulating PCSK9 and 6-month cardiac magnetic resonance (CMR) imaging-derived left ventricle ejection fraction (LVEF) after a first ST-segment elevation myocardial infarction (STEMI). Methods We prospectively evaluated 40 patients with a first STEMI treated with primary percutaneous coronary intervention (PPCI) and LVEF Results The mean age of the sample was 60±12 years and 33 patients (82.5%) were male. Mean 1-week and 6-month LVEF were 41±7% and 48±10%, respectively. The mean±SD of PCSK9 was 1.93±0.38 U/mL. PCSK9 values were inversely related with 6-month LVEF (r=−0.35, p=0.028). The mean values of PCSK9 were significantly higher in patients with LVEF Figure 1 Conclusions In patients with a first STEMI treated with PCCI and reduced ejection fraction, circulating PCSK9 was associated with lower LVEF at 6 months.

Background The microscopic consequences in the myocardial capillaries after myocardial infarction (MI) have been widely addressed, but little attention has been paid to epicardial coronary arteries. Since epicardial circulation is responsible for providing blood flow to the heart, understanding the microscopical changes on the epicardial artery after MI becomes also crucial. Purpose To evaluate the dynamics of the microscopic damages in the coronary arteries post-MI in swine model of reperfused MI. Methods MI was induced in swine by transient 90-min coronary occlusion of the left anterior descending (LAD) coronary artery using angioplasty balloons. One control group and four MI groups were defined: 1) without reperfusion, and 2) 1-min, 3) 1-week, and 4) 1-month reperfusion (n=3, each). In each group, LAD (infarct-related artery) and the right coronary artery (RCA) were isolated. Taking as reference the region in which balloon was inflated, we also separated samples from two different regions: proximal and distal LAD. Histological stainings (HE, Masson's trichromic, and orcein) and immunohistochemistry against CD31 (endothelial cells), a-smooth muscle cells, and CD45 (total leukocytes) were performed. Results Abnormalities in the endothelial monolayer of the LAD artery started even before reperfusion (during ischemia). This damage dramatically increased after reperfusion, observing an almost absence of CD31+ cells in the tunica intima and some breaks in the internal elastic layer from the 1-min and 1-week reperfusion groups. No irregularities were found in the tunica media from the no reperfusion group, whereas an increased in its thickness was detected soon after reperfusion. In the 1-week reperfusion group, larger thickness, a desorganized muscular cells distribution, and oedema were found. The damage in the tunica intima and media was more pronounced in the region distal to the angioplasty balloon compared to the proximal region, whereas no changes were detected in the RCA. In the tunica adventitia, vasa vasorum density was reduced during the ischemic phase, remaining low in the 1-min and 1-week reperfusion group, while being restored after 1-month reperfusion. This dynamics was similar in both LAD regions, while no changes in the RCA were found. After coronary reperfusion, a higher leukocyte adhesion to the endothelium from the LAD artery, mainly in the region proximal to the balloon inflation, was observed. The process evolves, resulting in a massive presence of CD45+ cells not only in the tunica intima, but also in the media and the adventitia monolayer isolated from the 1-week reperfusion group. Conclusions The microscopic structure of the infarct-related coronary artery was compromised after MI. This damage started during ischemia and boosted after reperfusion, becoming more pronounced in the region distal to balloon inflation. Exploring these damages will be important for a better understanding of the pathophysiology of MI. Acknowledgement/Funding This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (PIE15/00013, PI17/01836, and CIBERCV16/11

Heart failure with mid-range ejection fraction (HFmrEF) has been recognized as a distinct HF phenotype, but wether patients on this category fare worse, similarly, or better than those with HF with reduced EF (HFrEF) or preserved EF (HFpEF) in terms of rehospitalization risk over time remains unclear. We therefore sought to characterize the mordibity burden of HFmrEF patients by evaluating the risk of recurrent hospitalizations following an admission for acute HF. Methods We prospectively included 2,961 consecutive patients discharged for acute HF in our institution from 2004 to 2017. Patients were categorized according to their ejection fraction (EF) obtained by an echocardiography during the index admission: HFmrEF (EF 41–49%), HFrEF (EF≤40%) and HFpEF (EF≥50%). Negative binomial regression method was used to evaluate the association between EF status and recurrent all-cause and HF-related admissions. Risk estimates were expressed as incidence ratio ratios (IRR). Results Mean age of the cohort was 73.9±11.1 years, 49% were women, and 46.0% had suffered from previous HF admissions. 472 patients (15.9%) had HFmrEF, 956 (32.3%) had HFrEF, and 1,533 (51.8%) had HFpEF. At a median (interquartile range) follow-up of 2.4 (4.4) years, 1,821 (61.5%) patients died and 6,035 all-cause readmissions were registered in 2,026 patients (68.4%), being 2,163 of them HF-related. Rates of all-cause readmission per 100 patients-years of follow-up were 43.4, 47.1 and 50.1 per HFrEF, HFmrEF and HFpEF categories, respectively. After multivariable adjustment, and compared to patients with HFrEF, HFmrEF status was not associated with a higher risk of all-cause or HF-related recurrent admissions (IRR=1.06; 95% confidence interval (CI), 0.93–1.20; p=0.89), and IRR=1.07; 95% CI, 0.91–1.26; p=0.389, respectively), whereas HFpEF status was associated with a non-significant increase in the risk of all-cause recurrent admissions but a similar risk of HF-related readmissions (IRR=1.10; 95% confidence interval (CI), 0.99–1.22; p=0.06, and IRR=1.01; 95% CI, 0.88–1.16; p=0.900, respectively) Conclusion Following an admission for acute HF, patients with HFmrEF have a similar all-cause and HF-related rehospitalization burden when compared to patients with HFrEF, by means of recurrent events analysis.

Background The interstitial space is mainly composed by cells, fibers and gels of polysaccharides, which act as a compression buffer against the stress placed on the extracellular matrix (ECM). After myocardial infarction (MI), heart has to withstand higher mechanical stress due to injured cardiomyocytes. ECM composition notably influences the mechanical properties of the myocardium and participates in left ventricular remodeling. Purpose To characterize the myocardial ECM changes from ischemia onset until late phases after coronary reperfusion in a swine model of reperfused MI. Methods MI was induced in swine by transient 90-min coronary occlusion using angioplasty balloons. One control group and three MI groups were defined: 1) without reperfusion, 2) 1-week, and 3) 1-month reperfusion (n=5, each). Myocardial samples from the infarcted area were isolated and histologically staining to evaluate the presence of collagen type I, collagen type III, elastic fibers, and proteinglycans. Moreover, the presence of laminin, fibronectin, and secreted protein, acidic and rich in cysteine (SPARC) was determined by immunohistochemistry. Five independent photographs for each group and each stain were taken and the presence of the different components of the interstitium was morphometrically quantified. Indeed, the mRNA levels of metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), and transcription factors implicated in ECM remodeling were quantified. Results In the no-reperfusion group, an increase in fibronectin, laminin, and elastic fibers were observed, whereas no changes neither in the quantity nor in the organization of collagen-I and collagen-III fibers were detected. In the 1-week and 1-month reperfusion groups, an augmentation in the content of collagen-I, collagen-III, elastic fibers were found. These fibers displayed a more organized pattern compared to control tissue. The quantity of proteinglycans, laminin, fibronectin, and SPARC were also increased. These changes could be explained by a heightening in the mRNA expression of TIMP1, TIMP2, and TIMP3 from the ischemic period until chronic phases, whereas no changes were observed for TIMP4. MMP2 and MMP9 mRNA levels were boosted in late phases post-MI. When exploring the mRNA levels of transcription factors implicated in ECM remodeling, CTGF increased during the ischemic period, whereas TNF-α and TGF-β augmented after 1-week and 1-month post-reperfusion, respectively. Conclusions ECM remodeling starts after ischemia onset, probably aiming to protect cardiomyocytes from the ischemic damage. After reperfusion, the ECM evolves to constitute a fibrotic scar to maintain a proper cardiac function. These changes may be orchestrated by the fluctuation in genes specially implicated in ECM distribution. ECM changes might be accurately regulated since it could provoke an adverse left ventricular remodelling, consequently impairing patient prognosis. Acknowledgement/Funding This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (PIE15/00013, PI17/01836, and CIBERCV16/11

[EN] Conclusion: Assessment of infarct size and MVO with cardiac MR imaging soon after STEMI enables one to make a decision in the prediction of reverse remodeling. (C) RSNA, 2015, Supported by the Instituto de Salud Carlos III and FEDER (grant PI1400271) and the Generalitat Valenciana (grant PROMETEO/2013/007).

Purpose: In the context of myocardial infarction (MI) the availability of metabolites is clearly restricted, therefore a fuel metabolic shifts takes place. Previous studies have indicated that peroxisome proliferator activated receptor co-activator alpha (PGC-1α) pathway is a crucial regulator of cardiac metabolism in response to cardiac stress. Here we address the role of PGC-1α in regulating metabolic changes of MI. Methods: We studied a group of 12 common swine in which anterior MI was induced by means of angioplasty balloon inflation. A series of 6 swine were sacrificed at 48h post-infarction (acute infarction group) and another series of 6 swine were sacrificed at 3 weeks (chronic infarction group). Metabolites such as: glucose, pyruvate, ketone bodies, and lipids were analyzed in serum (mmol/L) at baseline, 75 min after balloon inflation, 2 h, 48 h and 3 weeks after reperfusion by means of enzymatic analysis. Results were compared to baseline levels. Genes related to PGC-1α such as: PGC-1α, ERR-α, PPAR-α, and HIF-1α, were analysed (fold change) in infarcted, adjacent and remote areas of porcine hearts 48h or 3 weeks post-infarction by molecular biology. Results were compared to 5 control swine without infarction. Results: In all groups, after 2h of infarction, a striking increase of lactate (3.2 ± 0.6 vs. 0.8 ± 0.3) and non-esterified fatty acids (0.6 ± 0.2 vs. 1.8 ± 0.3) was observed in serum compared to baseline (p

Purpose: Fibrosis plays a key role in the pathophysiology of left ventricular (LV) remodelling after myocardial infarction (MI). The dynamics of this process and whether it is a localized or diffuse phenomenon has not been totally clarified. We aimed to characterize these issues in a swine model of reperfused anterior MI. Methods: Swine were subjected by means of percutaneous balloon inflation to a transient 90-min occlusion of mid left anterior descending artery followed by 72-h (acute MI model) or 1-month (chronic MI model) reperfusion. The extent of fibrosis was macroscopically (triphenyltetrazolium staining, % of LV volume) and microscopically (Sirius red staining, % of field) quantified in the infarct, adjacent and remote areas as well as in controls. TGF-β1, collagen1-A1, A2 and 3A1 gene expression was determined. Results: Macroscopically, necrosis (16±5% in the acute MI model) and fibrosis (16±4% in the chronic MI model) were detected in all cases. Macroscopic fibrosis occurred in the infarct but not in the adjacent or remote areas (Figure). At microscopic level, in comparison with controls, fibrosis was only significantly increased in the chronic MI model at the infarct area (35±4%, p

Purpose: Using cardiac imaging techniques it has been demonstrated that, after successful coronary revascularization of acute myocardial infarction (MI), microvascular obstruction (MVO) resolves spontaneously. Data on the course of this process in “in vivo” models are scarce. We aimed to characterize the dynamics of MVO in a swine model of reperfused anterior MI. Methods: Swine were subjected, by means of percutaneous balloon inflation, to a transient 90-min occlusion of mid left anterior descending artery followed by 72-h (acute MI model) or 1-month (chronic MI model) reperfusion. Area at risk (thioflavin-S staining) and the extent of MVO (% of area at risk without thioflavin-S staining) were quantified. Microvessel density (using immunohistochemistry by von Willebrand factor antibody, vessels/field) and the expression of Hypoxia Induced Factor-1α (HIF-1α mRNA) were determined in controls and in the acute and chronic MI models. Results: In the acute MI model, MVO (8.4±4.5%) was detected in all cases. MVO significantly decreased in the chronic MI model (0.14±0.09%, p

Programmed death-1 (PD-1) and Programmed death-1 ligand (PD-L1) regulate immune response. Previous studies associate an immune deregulation in ST-elevation myocardial infarction STEMI. We recruited 100 patients with a first STEMI treated with reperfusion. In all patients PD-1 and PD-L1 expression was studied 24 h post-reperfusion in peripheral blood mononuclear cells (PBMCs), by means of flow cytometry and molecular biology. PD-1 and PD-L1 expression was serially analyzed in the first 20 patients before reperfusion and 24h, 96h and 30 days afterwards. Results were compared with 30 age- and sex-matched controls. Cardiac Magnetic Resonance was used to quantify infarct size 1-week after infarction. In a series of 8 swine with induced STEMI, PD-1 and PD-L1 expression was analyzed at baseline, 90 min after balloon inflation, 2 h and 24 h after reperfusion in PBMCs, and in swine hearts. Results were compared to 5 controls. In patients, in comparison with controls, a significant decrease of PD-1 expression [mRNA fold change 0.8 ± 0.3 vs. 1.2 ± 0.6] and an increase of PD-L1+ expression [mRNA fold change 2.7 ± 2.1 vs. 0.9 ± 0.5] was observed 24h after infarction in PBMCs (p