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Funding Acknowledgements Type of funding sources: None. Introduction Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. Objective Evaluate the incidence of post-discharge thromboembolic and bleeding events and the role of thromboprophylaxis among COVID-19 patients. Methods We systematically searched PubMed, Embase and Cochrane databases, in March 2022, for interventional and observational studies. Results A total of 3 studies were included, providing a total 1569 patients, 325 in post-discharge anticoagulation and 1271 no discharge anticoagulation. In terms of outcomes assessed, both groups had similar symptomatic venous thrombotic events (pooled OR 0.43 [0.05, 3.79], P=0.14, I2=50%) and combined symptomatic and asymptomatic events pooled OR 0.63 [0.14, 2.79], P=0.54, I2=34%). Regarding bleeding events, no statistically significant difference was observed in all bleeding (major and non-major) events (pooled OR 2.85 [0.71, 11.43], P=0.14, I2=50%). Conclusion According to our meta-analysis, in patients hospitalized with COVID-19, extended thromboprophylaxis does not provide additional clinical benefit.

Introduction The increase in life expectancy is a reality and cardiovascular disease incidence rises with it. The elderly are fragile patients with high prevalence of multiple comorbidities. Anaemia is one of them and, in most cases, has multifactorial causes. After an acute coronary syndrome (ACS), the thrombotic versus haemorrhagic risks in these patients are hard to balance. Aim The aim of this study is to evaluate prognostic impact of anaemia in the elderly after an ACS. Methods Retrospective analysis of consecutive patients admitted to a single Intensive Coronary Unit between 2009 and 2016 with the diagnosis of ACS. Patients younger than 80 years old were excluded. A complete blood count was collected upon admission and anaemia was defined for haemoglobin values below 12.5mg/dL. Cox regression analysis and Kaplan-Meyer curves were conducted to determine prognostic value of anaemia in this specific population. Multivariate analysis with other comorbidities and antithrombotic therapy was also performed. Results A total of 353 patients (median age of 84.0±6.0 years old; 52.1% males; 51.3% with anaemia) were enrolled. In cox regression analysis, anaemia predicted mortality (HR 1.614; 95% CI 1.199–2.172; P=0.002). In multivariate analysis – including gender, presence of hypertension, diabetes, chronic kidney disease and atrial fibrillation (AF) at admission, anaemia proved to be an independent predictor of mortality (HR 1.521, 95% CI 1.119–2.069, P=0.007). Adding all previous and discharge antithrombotic therapy – antiplatelet inhibition and oral anticoagulants – to the equation, anaemia maintained its prognostic value (HR 2.157; 95% CI 1.130–4.116; P=0.020). Both AF and being discharged from the hospital with ticagrelor also increased mortality risk in these patients (HR 2.188, 95% CI 1.177–4.070, P=0.13 for AF; HR 1.906, 05% CI 1.011–3.594, P=0.046 for ticagrelor at discharge). Conclusions After an ACS, anaemia proved to be an independent predictor of mortality in the elderly. This emphasizes the importance of its adequate aetiology investigation and treatment and careful selection of antithrombotic therapy following an ACS. Funding Acknowledgement Type of funding sources: None.

Background The long-term survival rates of myocardial infarction with non-obstructive coronary arteries (MINOCA) patients is lower than in the general population. Nevertheless, there are conflicting results regarding the prognosis of MINOCA patients in comparison to myocardial infarction with obstructive coronary artery disease (MI-CAD) patients. Purpose The aim of this study was to assess the long-term all-cause mortality of MINOCA patients and compare it to MI-CAD patients. Methods Retrospective analysis of 2443 consecutively admitted patients for acute myocardial infarction (AMI), in a single coronary intensive care unit. Only patients with 5 years of follow-up and those who died before the 5-year mark were considered. Patients were divided into two groups according to the presence or absence of obstructive coronary artery disease on angiography (≥50% stenosis). Demographic characteristics, symptoms at presentation, past medical history, laboratory characteristics and medication at discharge were compared using the Mann-Whitney U or χ2 test (according to variable type) to ensure comparability between groups. Five-year all-cause mortality was the target endpoint. Five-year survival was modelled through the Cox proportional hazard regression model. The variable of interest (MINOCA vs MI-CAD) and possible confounders that displayed statistically significant differences in the initial demographic analysis were included in univariable Cox regressions, and those with statistically significant associations were included in a multivariable model. Those that displayed non-significant associations in the multivariable model were subsequently removed until we were left with significant associations only, giving us an adjusted hazard ratio. Results Comparison between groups is presented in table 1. MINOCA patients were younger and more often women. They were less likely to have smoking habits, diabetes, or a previous history of AMI. They had a lower Killip class, as well as lower troponin I, serum creatinine and low-density lipoprotein cholesterol at admission. On the other hand, they had higher left ventricular ejection fractions. They were also less likely to have beta-blockers or aspirin prescribed at discharge. All-cause mortality at 5 years was 13.1% among MINOCA patients and 28.3% among MI-CAD patients, with an unadjusted hazard ratio (HR) of 0.421 (95% CI 0.322–0.550), p Conclusions Compared with MI-CAD patients, those with MINOCA were slightly younger and had fewer comorbidities. In spite of having a worse long-term prognosis when compared to the general population, MINOCA patients have a significantly higher 5-year survival rate than MI-CAD patients, even after adjustment of confounding factors. Funding Acknowledgement Type of funding sources: None.

Background Critically ill patients hospitalized with COVID-19 are at high risk of developing major adverse cardiac events (MACE). Purpose This study aimed to identify independent predictors of MACE after intensive care unit (ICU) admission which could be used to identify high-risk patients who may benefit from preventive strategies. Methods We retrospectively analyzed patients consecutively admitted to an ICU with COVID-19 and followed them for a median period of 7 months. Patients admitted due to trauma or emergent surgery were excluded. Logistic regression analysis was performed to evaluate which clinical characteristics predicted MACE. MACE was defined as all-cause ICU mortality, new-onset heart failure, acute coronary syndrome, ventricular arrythmias, pulmonary embolism, myocarditis, and stroke (ischemic or hemorrhagic). Results A total of 297 patients was included in the analysis. Median age was 62 (IQR 17) years, and most patients were male (198 patients, 66.7%). From a total of 297 patients, 108 (36.4%) developed at least one MACE: ICU all-cause mortality (92 patients, 31.0%), new-onset heart failure (27 patients, 9.1%), acute coronary syndrome (7 patients, 2.4%), ventricular arrythmias (7 patients, 2.4%), pulmonary embolism (13 patients, 4.4%), myocarditis (4 patients, 1.3%), and stroke (5 patients, 1.7%). Univariate logistic regression analysis showed that the clinical variables associated with MACE were male sex, older age, APACHE II score, SAPS II score, hypertension, hyperlipidemia, known coronary artery disease, heart failure, new-onset atrial fibrillation, need for invasive mechanical ventilation, duration of mechanical ventilation, and vasopressor use. In multivariate logistic regression analysis, we found that the MACE's independent predictors were older age, higher APACHE II score, and new-onset atrial fibrillation. Main results are presented in Table 1. Conclusion(s) Among critically ill COVID-19 patients, older age, higher APACHE II score, and new-onset atrial fibrillation independently predicted MACE. Funding Acknowledgement Type of funding sources: None.

Introduction Long QT syndrome (LQTS) is a rare heterogeneous syndrome that may be congenital or acquired, the latter being more common. Its real-world prevalence remains to be determined. We aimed to determine the prevalence of this syndrome in patients admitted to the emergency room (ER) and characterize the subset of patients with severely prolonged QT. Methods A retrospective analysis of ECG of all consecutively admitted patients in the ER of a tertiary hospital between the 28th of January and the 17th of March 2020 was made. All patients with Bazzett corrected QT interval greater than 470ms in men and 480ms in women were included. Repeated ECGs or with bad electrocardiographic quality, congenital LQTS, atrial fibrillation and pacemaker rhythm were excluded. Clinical data with a special focus on QT prolonging drugs and clinical factors were recorded. Statistical comparison was made between the groups with and without QT interval greater than 500ms. Results A total of 6280 ECGs of 5056 patients were analysed. After evaluation, 390 ECGs from 387 different patients were considered. Prevalence of LQTS at admission was 7.95%. Patients were more commonly men (53.1%) with an average age of 73.6±14.7 years old and mean QTc interval of 502.14±32.2ms. Only 20% of the patients were symptomatic, with the most common form of presentation being syncope (50%). No ventricular arrhythmias were recorded. Regarding patients with a QT interval greater than 500ms, these were more frequently female (59.9% vs 37.2%, p Conclusions Acquired LQTS is particularly prevalent in the ER setting. The complex interaction of clinical factors and drug iatrogenesis and the unpredictability of its manifestations render its management and recognition difficult but essential. Female patients on antibiotics and antipsychotics are at particularly high risk. Efforts must be made in order to avoid, detect and treat acquired LQTS as early as possible. Funding Acknowledgement Type of funding sources: None.

Introduction Heart failure with mildly reduced ejection fraction (HFmrEF) has been recognized in the last heart failure guidelines of the European Society of Cardiology, replacing the concept of “midrange ejection fraction”. There is limited data regarding mortality outcomes of HFmrEF compared to heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction. Purpose We aimed to evaluate whether HFmrEF has a different prognosis after an acute heart failure (AHF) episode, in a real-world contemporaneous southern European population. Methods We retrospectively studied 1026 patients admitted to our emergency department between November 2016 and December 2017 with discharge diagnosis of AHF. Median follow up was 5 months (IQR 3–11 months). Incidence of rehospitalization, cardiovascular (CV) and all-cause mortality were evaluated through multivariable logistic regression models and by Kaplan-Meyer survival curves. Results From all patients, 782 were categorized in HFrEF (34.1%), HFmrEF (19.4%) and HFpEF (46.4%). There was heterogeneity between groups. Compared to HFrEF, HFmrEF patients were older (80 [74–84] vs. 76 [67–82] years, p Conclusions HFmrEF have a similar prognosis to HFrEF and worse than HFpEF, with more readmissions, CV and all-cause mortality, after an AHF episode. Funding Acknowledgement Type of funding sources: None.

Background The association between atrial fibrillation (AF) and prognosis has been studied in non-COVID-19 patients, but few studies reflect the reality of critically ill COVID-19 patients admitted to a general intensive care unit (ICU). Purpose This study sought to investigate the relationship between previous and new-onset AF in COVID-19 patients admitted to an ICU and prognosis. Methods We retrospectively analyzed patients consecutively admitted to an ICU with COVID-19 and followed them for a median period of 7 months. Patients admitted due to trauma or emergent surgery were excluded from the analysis. Three groups were identified: without AF (G1), with prior history of AF (G2), and with new-onset AF (G3). Groups were compared, with special interest regarding ICU mortality, duration of mechanical ventilation, length of hospitalization, major adverse cardiac events (MACE), and re-hospitalization. MACE was defined as all-cause ICU mortality, new-onset heart failure, acute coronary syndrome, ventricular arrhythmias, pulmonary embolism, myocarditis, and stroke (ischemic or hemorrhagic). Results A total of 297 patients was included in the analysis: without AF (248 patients, 83.5%), with prior history of AF (15 patients, 5.1%), and with new-onset AF (34 patients, 11.4%). Median age was 62 (IQR 17) years, and most patients were male (198 patients, 66.7%). Patients with a prior history of AF were older [median (IQR), G1 60 (16), G2 71 (12), G3 67 (15) years, p=0.001], were more likely to have a history of coronary artery disease (G1 4.9%, G2 26.7%, G3 11.8%, p=0.002), and history of heart failure (G1 6.5%, G2 33.3%, G3 17.6%, p In multivariate analysis, new-onset AF (OR 3.07, 95% CI 1.42–6.67, p=0.005) and older age (OR 1.07, 95% CI 1.04–1.09, p Conclusion(s) This study shows that critically ill COVID-19 patients with AF present a worse prognosis compared to patients without AF, and new-onset AF is an independent predictor of ICU mortality and MACE. Funding Acknowledgement Type of funding sources: None.

Introduction Aortic stenosis (AS) is highly age-related, and its prevalence is increasing rapidly in high-income countries. There are 2 major types of amyloid protein responsible for cardiac amyloidosis (CA) - transthyretin (TTR) and immunoglobulin lightchain (AL). Previous cohorts report an incidence ranging from 9 to 16% for the presence of CA in patients with AS referred for TAVR. These patients appear to have a similar prognosis to those with lone AS when undergoing TAVR, but a trend toward worse prognosis if left treated. We aimed to investigate the prevalence of CA in patients with severe AS referred for TAVR in the Portuguese population. Methods We prospectively recruited 60 consecutive patients referred for TAVR at our tertiary center between November 2020 and May 2021. 59 patients agreed to participate and signed an informed consent, approved by the local Ethics Commission. All patients performed coronary angiogram, echocardiogram, thoracic abdominal pelvic CT scan, ECG, bone scintigraphy (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid [DPD]) and blood and urine monoclonal immunoglobulin testing. (Figure 1). Results About half (54.2%) of patients were male, average age was 82 years and the prevalence of ischemic heart disease and cardiovascular risk factors was high. About one third of patients had atrial fibrillation and 27.1% were pacemaker carriers. Echocardiographic baseline findings were: maximum aortic valve gradient 72.77±18.18 mmHg; mean aortic valve gradient 43.49±11.60; aortic valve area 0.65±0.15 cm2; interventricular septum thickness 1.30±0.23 cm; left ventricular ejection fraction (LVEF) 52.06±11.35%; E/E' 14.63±7.5; tricuspid annular plane systolic excursion 19.2±4mm; right ventricle/ right atrial gradient 38.1±14.32mmHg. CA was diagnosed in 6 (10.2%) patients. Perugini grade was 1 (n=3) and 3 (n=3). One patient (Perugini grade = 3) was found to have plasma cell dyscrasia, producing monoclonal IgG Kappa protein. CA patients were all male, older (86.5 vs 81.30 years, p=0.049), more frequently pacemaker carriers (66.7 vs 22.6%, p=0.041) and had a tendency to have a thicker interventricular septum (1.48 vs 1.28 cm, p=0.065). Conclusions We show that in the Portuguese population, the prevalence of CA in severe AS patients referred for TAVI is in line with what is observed in other countries. This has important consequences regarding the diagnosis and management of these patients. Funding Acknowledgement Type of funding sources: None.

Background The incidence and pathogenesis of sudden death (SD) in the young adult population in Portugal remains to be clarified. Some of the causes are known to be hereditary and a better understanding of these can have implications on the development of a national screening program for relatives of SD victims. Purpose To describe the leading causes of sudden cardiac and non-cardiac death in a young adult Portuguese population (≤40 years-old). Methods The authors retrospectively reviewed cases from a national database regarding individuals who underwent an autopsy, between 2012 and 2016, at 6 districts of mainland Portugal plus the islands. All young adults (1–40 years-old) who had a sudden unexpected death were included and violent deaths were excluded. This study was approved by the Institute Ethics Committee. We reviewed the autopsy files and collected demographic, clinical, necropsic, anatomopathological and toxicological data from each case. We performed statistical analysis using Stata 13.0 software. Results During a 5-year period, out of an estimated total of 2101 deaths in ages 1 to 40, 175 SD were identified. SD victims had a mean age of 32±9 years-old, the majority being of male gender (69%,n=120). There were 115 (66%) cases of SD of confirmed cardiac origin (see Table 1). The remaining causes were respiratory (18%), cerebral (7%), digestive (6%), endocrinologic (2%), urinary (1%), infectious (1%). The most frequent cardiac cause being coronary atherosclerosis (n=40,35%), which included lesions with estimated luminal narrowing >75% and/or documented type 1 acute myocardial infarction. These patients were older (31±8 vs 35±4, p Conclusions During a 5-year period, the cumulative incidence of SD in a region of Portugal is very low (n=175), cardiac causes being present in 66% of the cases. The most frequent cardiac cause is coronary atherosclerosis (35%). Funding Acknowledgement Type of funding sources: None.

Introduction Early rhythm-control therapy of atrial fibrillation (AF) (including catheter ablation) has been established as significantly lowering risk of adverse cardiovascular outcomes and improving overall survival and quality of life. Obstructive sleep apnoea (OSA) is a common but often overlooked comorbidity in patients with AF that may lead to difficulties in maintaining sinus rhythm. Data on the impacts of its treatment on recurrence remain conflicting. Objective To determine the prevalence of OSA in a population of AF patients submitted to catheter ablation and its impact on recurrence after a successful procedure. Methods Retrospective study of patients with AF consecutively submitted to catheter ablation in a tertiary centre between January 2017 and December 2020. The main outcome was AF recurrence after ablation. Sociodemographic variables and clinical data were retrieved for each patient, including type of AF, comorbidities, screening and diagnosis of OSA, treatment of OSA prior to ablation, time from ablation to recurrence of AF, method of ablation (radiofrequency or cryo). Statistical comparison between patients with and without OSA was made, including survival curves and Cox regression to determine time to recurrence and adjust for confounding variables. Results A total of 189 patients were included with a mean age of 63.49±11.09 years. Mean follow-up time after ablation was 2.76±1.56 years. Patients who recurred after ablation had undergone more electrical cardioversions prior to the procedure (1.640±1.583 vs 0.800±0.966, p 0.002), had more persistent AF (p 0.036) and had more OSA (32.7% vs 15.7%, p=0.011). There were no differences regarding age, gender, body-mass index, history of hypertension, diabetes, chronic kidney disease or heart failure, method of ablation and diagnosis of OSA prior to ablation. Forty-nine patients (18.7%) had OSA, with only 16 (32.7%) having been diagnosed before ablation. OSA was screened in only 60 cases (31.7%), mostly due to symptoms (76.1%) and not per protocol. Patients with OSA had earlier recurrence of AF after ablation (p Log-rank 0.012) with a hazard two times greater of recurrence, even after adjusting for confounding (p 0.026; hazard-ratio 2.025; confidence interval 95% 1.086–3.775). One year recurrence rate was 31% in patients with OSA (vs 15%). Regarding patients under treatment for OSA prior to ablation, there was no difference in survival (p Log-rank 0.859). Conclusion In real-world practice, OSA is still a largely underinvestigated condition that significantly impairs AF control and contributes to worse cardiovascular outcomes. Recurrence was 2 times higher in patients with OSA. No impact of treatment in time to recurrence was found. Efforts must be made to increase screening of this condition in order to improve outcomes. Further studies are needed to clarify the benefits of OSA treatment in AF recurrence. Funding Acknowledgement Type of funding sources: None.

Background Tricuspid Regurgitation (TR) is common in patients with severe mitral disease. However, the evidence is insufficient to inform a decision about whether to perform prophylactic tricuspid-valve repair during mitral-valve surgery in patients who have moderate TR or less-than-moderate regurgitation. Purpose To compare the outcomes of concomitant tricuspid repair in mitral valve surgery versus no concomitant tricuspid repair in less-than-severe TR patients. Methods We systematically searched PubMed, Embase and Cochrane databases, in December 2021, for interventional studies comparing concomitant tricuspid repair in mitral valve surgery versus no tricuspid intervention. Random-effects meta-analysis was performed. Results Four randomised trials were included, providing a total of 651 patients (323 in prophylactic tricuspid intervention group and 328 patients in conservative group). Our meta-analysis showed a similar all-cause mortality for concomitant prophylactic tricuspid repair compared with no tricuspid intervention (pooled OR, 0.54; 95% CI [0.25, 1.15], P=0.11; I2=0%). Additionally, there is a similar New York Heart Association (NYHA) III–IV classes in both groups, despite a lower trend in the tricuspid intervention group (pooled OR, 0.63; 95% CI [0.38, 1.06], P=0.08; I2=0%) (Figure 3). However, there was a significant lower progression of TR (pooled OR, 0.06; 95% CI [0.02, 0.24], P Conclusions Our pooled analysis suggests that a tricuspid-valve repair at the time of mitral-valve surgery in patients with moderate or less-than-moderate TR does not impact perioperative or postoperative all-cause mortality, despite reducing TR severity and progression of TR following intervention. Funding Acknowledgement Type of funding sources: None.

Background Carotid stenosis is responsible for a considerable amount of strokes and related deaths. Carotid angioplasty stenting (CAS), endarterectomy (CEA) and best medical treatment (BMT) are important in preventing major cardiovascular (CV) events. Methods We conducted a systematic review and meta-analysis, with randomized controlled trials (RCT), to compare CAS with CEA and BMT regarding the short and long-term major periprocedural and follow-up CV events (stroke, myocardial infarction, and death) in symptomatic and asymptomatic carotid stenosis. We searched for RCT published from 2008 to 2021 in databases such as Pubmed/MEDLINE, B-On, Embase, Clinical Trials from U.S. National Library of Medicine and International Clinical Trials Registry Platform, between July of 2018 and January of 2019, and in October of 2021. Results Nine RCT were included, with a total of 9162 participants for CAS versus (vs) CEA, and 513 participants for CAS vs TMO. Compared with CEA, CAS is associated with periprocedural stroke and death in symptomatic patients (HR=1.65, 95% CI: 1.29–2.11, p=0.05, I2=62%), due to higher stroke events than deaths. That association does not occur in asymptomatic patients in which CAS is not associated with periprocedural stroke or death (CAS=8.55%, CEA=7.05%, p=0.09). During follow-up there were no significant differences between CAS and CEA in symptomatic patients regarding stroke (HR=1.51, 95% CI: 1.23–1.84, p=0.57, I2=0%) and death (HR=1.10, 95% CI: 0.93–1.30, p=0.69, I2=0%). Periprocedural myocardial infarction (MI) incidence is higher in CEA (CAS=1.1%; CEA=2.3%; p=0.03), without influence of symptomatic status. CAS is not inferior to CEA, in both symptomatic and asymptomatic patients with high surgery risk, as for periprocedural and one year CV major events (CAS=12.2%, CEA=20.1%, absolute difference = −7.9, 95% CI: −16.4–0.7, p=0.004). BMT had no significant findings vs CAS in asymptomatic patients (HR=3.5, 95% CI: 0.42–29.11, p=0.246). Conclusion CAS is not inferior to CEA as for the periprocedural and one-year major CV events in patients with normal surgery risk. However, there is a higher risk of periprocedural stroke in CAS for symptomatic patients, and of periprocedural MI in CEA with no influence of symptomatic status. CAS seams to prevent middle and long-term ipsilateral stroke in symptomatic patients. BMT has yet to prove not to be inferior to CAS in asymptomatic patients. Funding Acknowledgement Type of funding sources: None.

Background Among patients with an aborted episode of malignant ventricular arrhythmias without a reversible cause, the Implantable Cardioverter Defibrillator (ICD) is considered an important therapy for secondary prevention of sudden cardiac death (SCD). Some authors propose primary catheter ablation and deferred ICD implantation may be the preferred approach in patients with substrate-related ventricular tachycardia. Purpose We want to evaluate the need of secondary time ablation in patients with secondary prevention ICD, when submitted only a medical therapy after the index event. Methods We conducted a retrospective, observational study of 90 patients who consecutively implanted ICD after an aborted episode of malignant ventricular arrhythmias without a reversible/known cause between 2014 and 2020. Patients with Brugada Syndrome, Wolff-Parkinson-White syndrome, QT related diseases and previous ventricular tachycardia (VT) ablation were excluded. Baseline clinical characteristics were analyzed, and a 1-year follow-up was performed: cardiovascular (CV) death, sustain VT), ventricular fibrillation (VF), antitachycardia pacing (ATP), ICD shock, VT ablation. Results Mean age was 58±18 years, 80% (n=72) were male and 65.5% (n=59) had a non-ischemic etiology. Most of the patients (61%; n=56) present with hemodynamic unstable VT or syncope, and 38% (n=34) with SCD [most due to VF (n=30)]. After the index event 41.1% (n=37) and 83.8% (n=75) initiate antiarrhythmic and beta-blocker (BB), respectively. During 1-year follow-up (FUP) 11.1% (n=10) had a sustain VT and 2.2% (n=2) VF leading to ATP and appropriated shock in 11.1% (n=10) and 10% (n=9), respectively. There was 2 CV death [due to acute heart failure (HF)], 8 HF hospitalization and 3 VT ablation during follow-up. The presence of chronic kidney disease at baseline was the only parameter related to 1-year CV death (1.3% vs 18.2%, p=0.039) and HF hospitalization (0% vs 18.2%, p=0.014). The antiarrhythmic after index event was associated with a significant less sustain VT [10% vs 45%, OR 0.114 (IC 95% 0.014 to 0.927] and consequently ATP (adjusted for age) and had a numerical benefit in ICD shock (2.7% vs 15.1%, p=0.076) and need of a secondary time ablation (0% vs 5.7%, p=0.266). Conclusion The ICD implant with antiarrhythmic therapy, as a primary approach to secondary prevention (vs ablation), after an aborted episode of malignant ventricular arrhythmias still showed to be a secure and viable first option. Funding Acknowledgement Type of funding sources: None.

Background Aortic stenosis (AS) is the most common valvular disease in developed countries. Specific timing of intervention for asymptomatic patients with severe aortic stenosis and preserved ejection fraction remains controversial. Purpose To compare the outcomes of early aortic valve replacement (AVR) versus watchful waiting (WW) in asymptomatic AS patients with preserved ejection. Methods We systematically searched PubMed, Embase and Cochrane databases, in November 2021, for both interventional or observational studies comparing early-AVR with WW in the treatment of asymptomatic severeAS with preserved ejection fraction criteria. Random-effects meta-analysis was performed. Results Eight studies were included in which two were randomized clinical trials. A total of 2672 patients were included, providing a 642 pooled death events (327 in early-AVR and 941 in watchful waiting). In our meta-analysis, early-AVR revealed a significant lower all-cause mortality (pooled OR, 0.39; 95% CI [0.30, 0.51], P Conclusion Our pooled data suggests that early-AVR strategy is preferable for asymptomatic severe AS patients with preserved ejection fraction. Funding Acknowledgement Type of funding sources: None.

Introduction Cardiopulmonary exercise testing (CPET) is recommended in patients with heart failure (HF) to optimize exercise prescription and as part of the evaluation for heart transplantation. Hemodynamic gain index (HGI) derived from CPET has been proposed as a new marker of risk stratification in general population cohorts. Purpose We aimed to evaluate the prognostic value of HGI in patients with HF. Methods We conducted a single-centre study assessing consecutive patients with HF who underwent CPET from 2013 to 2017. HGI was calculated based on heart rate (HR) and systolic blood pressure (SBP): HGI = [(HRpeak × SBPpeak) − (HRrest × SBPrest)] / (HRrest × SBPrest). Classic and recently proposed variables were collected, including peak O2 uptake (pVO2), minute ventilation–CO2 production (VE/VCO2 slope), circulatory power (CP = pVO2 × peak SBP), and ventilatory power (VP = peak SBP/(VE/VCO2) slope). The primary outcome was a composite of HF hospitalization, heart transplant, and all-cause mortality. Results A total of 212 patients (mean age 55.4±10.9, 76.9% male) were included. Most patients had dilated cardiomyopathy (43.9%) followed by ischaemic aetiology (38.7%), with a mean left ventricle ejection fraction of 29±13%. The most used exercise protocol was the modified Naughton (76.6%), followed by the original Naughton (18.7%), and Bruce (4.8%). Mean pVO2 was 16.7±5.9mL O2 kg–1 min–1 and median VE/VCO2 slope was 37.5 [32.7–44.3]. Mean VP was 3.46±1.31mmHg while median CP was 1927 [1427–2697]mmHg min/mL/kg. Mean HGI was 0.90±0.5 bpm/mmHg. Despite weak, there were significant positive correlations between HGI and mean pVO2 (rs=0.55, p1.02). After a median follow-up of 71 [49–81] months, the primary outcome occurred in 66.0% of patients (rehospitalization, heart transplant, and all-cause death occurred in 56.1%, 25.9%, and 32.5%, respectively). In the T1 group, the multivariable-adjusted odds ratio (OR) for the primary outcome was 3.73 (95% CI 1.97–7.06, p Conclusion HGI is inversely associated with the composite of HF hospitalization, heart transplant, and all-cause mortality in patients with heart failure, enhancing the role of CPET in risk stratification. Funding Acknowledgement Type of funding sources: None.

Background Rotational atherectomy (RA) enables percutaneous coronary intervention (PCI) for complex and calcified coronary lesions, despite limited data regarding long-term outcomes. Purpose We aimed to characterize success rate, safety, and long-term outcomes with this technique in a single-centre with over a decade of experience. Methods We retrospectively analysed all cases of RA performed in a single-centre between January 2009 and December 2020. Angiographic success was defined as the presence of less than 30% residual stenosis and grade 3 TIMI (thrombolysis in myocardial infarction) flow. Complications included coronary perforation or dissection, burr entrapment, wire fracture, slow flow/no-reflow, side branch occlusion, peri-procedural myocardial infarction (MI), or death. Long-term major adverse cardiovascular (CV) events (MACE) included CV and all-cause death, MI, and target vessel revascularization. Results Of the total of 14,527 PCI performed, 410 procedures (2.8%) included RA. Most patients were male (74.0%) with mean age of 72.3±9.3 years. There was high prevalence of hypertension (85.65%) and dyslipidaemia (74.2%) which increased significantly over time (p trend=0.008 and p trend Conclusions RA is an effective and safe technique, with a declining rate of peri-procedural complications along with technical developments. The rate of long-term events is concordant with the CV risk profile and coronary lesion complexity. Funding Acknowledgement Type of funding sources: None.

Background Aortic stenosis (AS) is the most common valvular disease in developed countries. However, the specific timing of intervention for asymptomatic patients with severe AS remains controversial. Purpose To compare the outcomes of early aortic valve replacement (AVR) versus watchful waiting (WW) in asymptomatic patients with AS. Methods We systematically searched PubMed, Embase and Cochrane databases, in December 2021, for both interventional or observational studies comparing early AVR with WW in the treatment of asymptomatic severe AS. Random-effects meta-analysis was performed. Results Thirteen studies were included in which two were randomised clinical trials. A total of 4,679 patients were included, providing a 1,268 pooled death events (327 in early AVR and 941 in WW). Our meta-analysis showed a significantly lower all-cause mortality for the early-AVR compared with WW group, although with a moderate amount of heterogeneity between studies in the magnitude of the effect (pooled odds ratio [OR], 0.41; 95% confidence interval [CI] 0.34, 0.50, P Conclusions Our pooled data suggest that an early-AVR strategy is preferable for asymptomatic patients with severe AS. Funding Acknowledgement Type of funding sources: None.

Introduction Renal dysfunction is one of the most important comorbidities in patients with chronic heart failure (HF) and frequently accentuated in the setting of acute HF (AHF). Serum creatinine and blood urea nitrogen (BUN) have been classically used as markers of renal dysfunction, despite having several limitations. High (BUN)/creatinine ratio has been associated with higher mortality in patients with HF. We aimed to predict the long-term outcome of patients admitted with acute heart failure to the emergency department using renal markers. Methods 900 patients admitted to our emergency department diagnosed with AHF were retrospectively analysed. Patients were divided into 4 groups according to BUN and SCr on admission: – BUN ≤33 mg/dL and SCr ≤1.56 mg/dL (group LowBUN/LowCr), n=544; – BUN ≤33 mg/dL and SCr >1.56 mg/dl (group LowBUN/HighCr), n=25; – BUN >33 mg/dL and SCr ≤1.56 mg/dL (group HighBUN/LowCr), n=131; – BUN >33 mg/dL and SCr >1.56 mg/dL (group HighBUN/HighCr), n=200; The primary end-point of this study was the occurrence of all-cause mortality during follow-up. Results The median (IQR) BUN level on admission was 28.0 (20) mg/dL, median (IQR) SCr level on admission was 1.15 (0.73) mg/d, mean age was 81±7 years, 50.8% (n=457) were women and median follow up was 7 months. A total of 41.2% patients were diabetic, 21.7% had at least mild COPD, CAD was present in 28.9% of cases, 44.0% had valvular heart disease and 68.4% patients had atrial fibrillation. Creatinine, BUN and Cr/BUN ratio predicted survival at 6 months (p Survival was the lowest in the group HighBUN/HighCr and the highest in the group LowBUN/LowCr. As expected, BUN/Cr ratio was the highest in group HighBUN/LowCr and the lowest in group LowBUN/HighCr. Conclusions Despite not having the highest BUN/Cr ratio, patients with BUN >33 mg/dL and SCr >1.56 mg/dL showed the worst prognosis. Funding Acknowledgement Type of funding sources: None.

Background Patients having transcatheter aortic valve implantation (TAVI) routinely undergo coronary angiography before the procedure to define the coronary anatomy and to evaluate the extend of coronary artery disease (CAD). Whether percutaneous coronary intervention (PCI) prior/concomitant with TAVI confers any additional clinical benefit in patients with CAD remains unclear. Purpose To compare the outcomes of PCI prior to TAVI in patients with significant coronary artery disease and severe aortic stenosis. Methods We systematically searched PubMed, Embase and Cochrane databases, in November 2021, for both retrospective and prospective studies comparing TAVI with PCI versus TAVI alone. Random-effects meta-analysis was performed. Results Eleven studies were included in which one was a randomized clinical trial. A total of 2530 patients were included, providing a 145 pooled death events (64 in TAVI with PCI and 81 in TAVI only). In terms of 30-day clinical outcomes, our pooled analysis revealed a similar all-cause mortality (pooled OR, 1.24; 95% CI [0.80, 1.93], P=0.34; I2=27% - Figure), cardiovascular mortality (pooled OR, 1.44; 95% CI [0.56, 3.75], P=0.45; I2=57%) and stroke (pooled OR, 1.07; 95% CI [0.53, 2.13], P=0.86; I2=0%). However, our analysis revealed a higher rate of myocardial infarction (pooled OR, 4.28; 95% CI [1.56, 11.69], P Conclusion Our pooled data suggests that PCI with TAVI in patients with severe aortic stenosis and concomitant CAD grants no additional clinical advantage. Funding Acknowledgement Type of funding sources: None.

Background The outcomes of dual anti-platelet therapy (DAPT), β-blocker, renin-angiotensin-aldosterone system (RAAS) inhibitor and statin therapy are unknown in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA). The aim of this study was to examine the effects of secondary prevention therapy at discharge on long-term outcomes in MINOCA. Methods Patients with MINOCA undergoing early coronary angiography between 2009 and 2016 were extracted from a clinical database. Patients were followed until 2018 for outcome events. All patients with a MINOCA diagnosis and without history of atrial fibrillation were included. A total of 646 consecutive patients were enrolled. The primary end point was major adverse cardiac events (MACE) defined as all-cause mortality, myocardial infarction (MI), stroke, and heart failure (HF). Secondary endpoints comprised all individual endpoints for the composite end-point. The relationship between treatments and outcomes was evaluated by using Kaplan-Meier survival analysis and Cox regression models. Results Mean age was 67.9±13.4 years and 31.6% were women. No patient was lost to follow-up. Mean left ventricular ejection fraction was 47.8±13.1%. At discharge, 87.2%, 82.5% and 79.5% of the patients were on statins, RAAS inhibitors and β-blockers, respectively. The majority (72.8%) were discharged on DAPT. During follow-up (Mdn 59 months), 303 (46.9%) patients experienced a MACE and 208 (33.4%) died. MI occurred in 98 patients (17.8%) and stroke in 31 patients (5.6%). HF admissions were also common (82, 14.9%). The hazard ratio (HR) for major adverse cardiac events was 0.31 (0.23–0.41) in patients on statins, RAAS inhibitors and β-blockers. For patients on DAPT the HR was 0.61 (0.48–0.78). In univariate Cox regression analyses, a reduced risk of MACE was found in patients using combined secondary prevention therapies (HR 0.58, 0.46–0.74). Regarding the individual endpoints, combined secondary prevention therapy reduced the risk of stroke (HR 0.45, 0.22–0.99, P=0.04) but not risk of future MI nor HF admissions. Patients in the combined therapy group had a higher median survival (66 months, IQR 27–82 months) than the group without secondary prevention (34.5 months, IQR 6.8–74 months; P Conclusions The results indicate long-term beneficial effects of treatment with secondary prevention medical therapies in patients with MINOCA. Properly powered randomized clinical trials are warranted. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: None. Background Malnutrition had been associated with worse prognosis in heart failure (HF) patients, especially in elder. However, this association wasn’t demonstrated in coronary patients, after a ST-segment elevation myocardial infarction (STEMI). We want to evaluate the prognosis value of malnutrition, in elder patients, after a STEMI. Methods We conducted a retrospective, observational study of 200 elderly patients (365 years) consecutively admitted with STEMI between 2016 and 2017. At discharge, we applied a validated formula who evaluate nutritional status: "Prognostic Nutritional Index" (PNI), [10 x serum albumin at discharge (g/dL) + 0.005 x total lymphocytes at discharge], whose lowest values were associated with malnutrition. At 1 year follow-up, we evaluated the relation between PNI and major adverse cardiac events (MACE): myocardial infarction (MI), HF hospitalization, cardiovascular (CV) and all-cause death. Results Mean age was 74±8 years, 71% (n=149) were male and with multiples risks factors (75% hypertense, 63% with dyslipidemia, 33% diabetes and 11% smokers). At discharge, patients had a mean Left Ventricular Ejection Fraction (LVEF) of 47±8% and a mean PNI of 37±5. Low PNI values (malnutrition) were significant associated with MACE at 1-year [OR 0.87 (95% CI 0.78 to 0.97, p=0.01)], after adjusting for age, sex and LVEF. When evaluated individually, low PNI was associated with more incidence of 1-year HF hospitalization [OR 0.88 (95% CI 0.78 to 0.99, p=0.03)] and all-cause death [OR 0.84 (95% CI 0.75 to 0.95, p=0.004)], after adjusting for age, sex and LVEF, but not with MI and CV death. Conclusion Malnutrion associated with other comorbidities inherent to elderly people were associated with MACE, 1-year after STEMI, in this type of population. Thus, we want to draw attention to the importance of evaluating the nutritional status during hospitalization for STEMI, allowing to initiate measures that contribute to its improvement.

Funding Acknowledgements Type of funding sources: None. Background The COVID-19 pandemic has shifted tremendously the paradigm of hospital care and treatment of cardiovascular (CV) patients. According to most recent evidence, due to its multisystemic impact, COVID-19 may lead to an increased risk of cardiac arrhythmias with subsequently increased morbimortality. Purpose Determine the prevalence of tachyarrhythmias in patients admitted with COVID-19, possible predictors and impact on in-hospital mortality. Methods A retrospective study of 3475 consecutive patients with COVID-19 pneumonia admitted to our hospital between February 2020 and November 2021 were included. The main outcome was tachyarrhythmias (high ventricular rate (HVR) or new-onset atrial fibrillation (AF), HVR or new-onset atrial flutter (AFL), other supraventricular tachycardias (SVT), ventricular tachycardia (VT) and ventricular fibrillation (VF)). Secondary outcome was in-hospital mortality. Sociodemographic variables and clinical data were recorded. Statistical comparison was made between groups, including logistic regression to determine odds ratios (OR). Results A total of 215 patients presented HVR AF (6.31%), 79 of which with new-onset AF (36.74%). 8 patients had HVR AFL (0.23%), 5 VT (0.15%), 4 VF (0.12%) and only 3 patients had a SVT identified (0.09%). Patients with tachyarrhythmias were significantly older (77. 74 ± 11.25 68.94 ± 17.51 years, p Patients with HF had the highest risk of tachyarrhythmia (OR 3.539; 95% CI 2.666-4.698; p Regarding the secondary outcome, patients with tachyarrhythmias during hospital stay had an odd almost 3 times higher of death (OR 2.820; 95% CI 2.151-3.695; p Conclusions Tachyarrhythmias is a common complication in COVID-19 patients during hospital stay that is significantly linked to higher in-hospital mortality. Patients presenting with high CV disease burden are at particularly significant risk and should be carefully managed.

Funding Acknowledgements Type of funding sources: None. Background The COVID-19 pandemic has had a dramatic impact on clinical practice, amounting to more emergency department and intensive care unit (ICU) admissions. Due to their frequent multiple comorbidities, management in the ICU is challenging. Early studies suggest that cardiac injury is frequent in hospitalized patients with COVID-19, and it is plausible that these patients have a higher risk of cardiac dysrhythmias. Purpose To determine the prevalence of dysrhythmias in ICU patients with COVID-19 pneumonia, identify major predictors and determine the impact on in-hospital mortality. Methods A retrospective study of 98 consecutive patients with COVID-19 Pneumonia admitted to the ICU of a tertiary hospital in 2020. The main outcome was dysrhythmias (including significant bradycardia, high/slow ventricular rate or new-onset atrial fibrillation (AF) or atrial flutter, other supraventricular tachycardias, ventricular tachycardia and ventricular fibrillation). Significant bradycardia was defined as heart rate lower than 40 or need of treatment. Sociodemographic variables and clinical data were retrieved for each patient, severity scores at admission (Apache II, SOFA and SAPS II), number of days on mechanical ventilation or high-flow oxygen and placement on Venovenous Extracorporeal Membrane Oxygenation (ECMO) or prone position were recorded. Statistical comparison was made between groups, including logistic regression adjusting for confounding variables. Results The most frequent arrhythmia was significant sinus bradycardia (28, 28.5%) followed by high ventricular rate AF (14, 14.2%). Patients who had dysrhythmias were older (66.24 ± 10.13 vs 60.85 ± 12.69 years, p 0.024), more severe (SAPS II score 42.55 ± 11.08 vs 35.98 ± 11.26, p 0.006), had more atrial fibrillation (AF) (p 0.022), had higher maximum C-reactive protein (mCRP) (6.56 ± 2.68 vs 6.24 vs 2.86, p 0.009), were mechanically ventilated for a longer time (15.64 ± 13.18 vs 8.92 ± 8.85 days, p 0.004), had longer intubation time (14.52 ± 9.39 vs 8.70 ± 8.21 days, p 0.002) and had higher usage of dexamethasone (p 0.042) and prone position (p 0.016). When adjusted for confounding variables, prone was the most significant predictor (OR 2.800; 95% CI 1.203-6.516) followed by use of dexamethasone (OR 2.484; 95% CI 1.020-6.050). Days intubated, days on mechanical ventilation, age, mCRP and SAPS II on admission were also predictors of dysrhythmia. Regarding mortality, patients with arrhythmic events had a tendency for greater in-hospital death (OR 2.440; 95% CI 0.950-6.310; p 0.065). Conclusions COVID-19 ICU patients are a subset of patients at risk of cardiac arrhythmias. Use of prone position was the main contributor to these events, but clinical history, severity and treatment may also play an important role. Efforts must be made to optimize ventilatory support and treatment in order to reduce the risk of dysrhythmias.

Funding Acknowledgements Type of funding sources: None. Background As heart failure (HF) is a progressive disease, there has been a raising idea that considering the absence of echocardiographic improvement as non-response to cardiac resynchronization therapy (CRT) may not be appropriate. In fact, in some classical echocardiographic non-responders, CRT might have prevented HF deterioration. Purpose Our aim was to compare the composite outcome of death and re-admissions due to HF according to a new classification of CRT response: responders, non-progressors and progressors. Methods We included 144 consecutive patients with HF, left ventricle (LV) ejection fraction < 40% and QRS duration > 120mseg submitted to CRT implantation. Patients were divided into 3 groups according to the variation of LV end-systolic volume (LVESV) at 6-month: ≥15% reduction in LVESV - responders (R); 0–15% reduction in LVESV – non-progressors (NPr); increase in LVESV – progressors (Pr). A long-term follow-up (4.9 ± 2.9 years) was performed targeting mortality and re-admissions due to HF. Results In our population, 78 patients (54.2%) were classified as R, 21 (14.5%) as NPr and 45 (31.3%) as Pr. Baseline comparison between groups is presented in table 1. Compared with R, N-Pr had ischemic aetiology more frequently. The prescription of digoxin was more common in Pr. The Kaplan-Meier curves (figure 1) demonstrate that the composite outcome of death and re-admission due to HF had a lower incidence in R, but was similar between N-Pr and Pr. After adjustment of possible confounders (ischemic aetiology and digoxin use), the type of response to CRT remained as the only predictor of outcomes (OR 0.61; CI 0.41-0.90). 144 Conclusion In our population, patients without progression of HF had a similarly negative prognosis to the ones that deteriorated. Hence, positive LV remodelling, and not only stabilization seems to be necessary to improve long-term prognosis.

Funding Acknowledgements Type of funding sources: None. Background In frail elderly patients or when atrioventricular block (AVB) is paroxysmal, and pacing anticipated to be infrequent, single chamber pacing (VVI or VDD) may be considered as it carries a lower complication rate compared with DDD devices. For sinus rhythm patients, the single lead VDD, by preserving atrial sensing, is a more physiological mode than VVI devices, with comparable time procedure and complication rates. However, there are few data assessing the performance of VDD pacemakers in elderly patients, with AVB and sinus rhythm. Purpose We want to evaluate the 3-years performance of VDD pacemakers (PM) in frailty elder patients with AVB. Methods We conducted a retrospective, observational study of 200 elderly (³75 years) patients with AVB and normal sinus rhythm who consecutively implanted VDD PM between 2016 and 2018. Baseline clinical characteristics were analyzed, and a 3-years follow-up was performed: atrial undersensing, atrial fibrillation (AF), heart failure (HF) hospitalization, cardiovascular (CV) and non-CV death. Results Mean age was 84±5 years and 55% were female. The study population presented several comorbidities: 74% had atrial hypertension, 49% dyslipidemia, 35% chronic kidney disease and 28% diabetes. After 3-years follow-up most of the patients (90%; n=162) were still programmed in their original mode with good atrial sensing. Due to permanent AF, 4%(n=8) patients had been switched to VVIR mode and 5.5% (n=11) due to P-wave undersensig. 0ne-third (n=65) died during follow-up, 89% (n=58) due to non-CV causes. Low amplitude P-wave ( Conclusion A significantly larger number of VDD-paced elderly patients maintain their original mode program with good atrial sensing. Moreover, atrial undersensing did not influence mortality or HF hospitalization rate. These results reinforce the benefit of VDD use among frail and elderly patients.

Funding Acknowledgements Type of funding sources: None. Background/Introduction It is now well known that patients with COVID-19 have a high prevalence of cardiovascular disease. COVID-19 is also associated with a substantial degree of cardiovascular involvement. However, the impact of cardiovascular disease (CVD) and cardiovascular risk factors on the natural history of COVID-19 is much less characterized. Purpose To characterize the prognostic impact of CVD and cardiovascular risk factors in COVID-19 patients admitted to an Intensive Care Unit (ICU). Methods We retrospectively analyzed patients consecutively admitted to an ICU with COVID-19, with a median follow-up of 10 months. Patients who either died or were discharged in the first 48 hours of admission were excluded. Three groups were identified: (1) established CVD – presence of either heart failure, coronary artery disease and/or peripheral artery disease; (2) at higher risk of CVD – arterial hypertension, dyslipidemia, diabetes mellitus and/or smoking, in the absence of established CVD; and (3) at lower risk of CVD – i.e. none of the above. Groups were compared, with special interest regarding in-hospital mortality, duration of mechanical ventilation, length of hospitalization. Global mortality (in-hospital and during follow up), and re-hospitalization were also compared. To compare survival, a Kaplan-Meier and multivariate Cox regression analysis were performed. Results Overall, 219 patients were identified, mean age was 62.1 ±11.9 years, 67.1% were male, 71 (32.4%) died in the ICU, 78 (35.6%) died during follow-up, and 14 (6.4%) were re-hospitalized. 30 patients (13.7%) had established CVD, 144 (65.8%) were at higher risk of CVD, and 45 (20.5%) were at lower risk of CVD. Patients with established CVD were older than patients at higher risk of CVD, and both were older than patients at lower risk (68.0 ±8.4 vs 62.0 ±11.3 vs 56.0 ±13.0 years, p Patients with established CVD were at significantly higher risk of ICU mortality (HR 2.42, 95% CI 1.08-5.46, p = 0.033), and higher risk of global mortality (HR 2.16, 95% CI 1.03-4.52, p = 0.042), compared to patients at higher and lower risk of CVD; in patients at higher and lower risk of CVD, ICU and global mortality was similar. In multivariate Cox regression, after adjusting for age and risk scores, established CVD was not an independent predictor of mortality. Kaplan-Meier survival curves are presented in figures 1 and 2. Conclusion(s) Almost 80% of patients admitted to an ICU with COVID-19 had established or were at higher risk of CVD. Patients with established CVD have a higher risk of death, although its presence is not an independent predictor of death.

Funding Acknowledgements Type of funding sources: None. Background/Introduction The association between NT-proBNP levels and prognosis in critically ill non-COVID-19 patients and non-critically ill patients has been studied, but few studies reflect the reality of critically ill COVID-19 patients admitted to a general intensive care unit (ICU). Purpose This study sought to investigate the relationship between NT-proBNP levels in COVID-19 patients admitted to an ICU and prognosis. Methods We retrospectively analyzed patients consecutively admitted to an ICU with COVID-19, with a median follow-up of 10 months. Patients who either died or were discharged in the first 48 hours of admission, and who did not have a NT-proBNP measurement in the first 48 hours, were excluded. Three groups were identified, based on ESC-endorsed, age-specific criteria for classification of NT-proBNP during acute presentations to categorize admission NT-proBNP levels into the following: (1) low ( 75,); and (3) high (>450 ng/mL for ages < 50; >900 ng/mL for ages 50–75; and >1800 ng/mL for ages > 75). Groups were compared, with special interest regarding ICU mortality, duration of mechanical ventilation, length of hospitalization, and in-hospital diagnosis of heart failure. Global mortality (in-hospital and during follow up), and re-hospitalization were also compared. To compare survival, a Kaplan-Meier and multivariate Cox regression analysis were performed. Results From a total of 219 patients, 72 (32.8%) had NT-proBNP on admission and were included in the analysis. Mean age was 64.9 ±10.3, 72.2% were male, and median NT-proBNP was 249 (IQR = 1161) pg/mL. Using age-specific criteria, 37 patients (51.4%) had low, 18 (25.0%) borderline, and 17 (23.6%) high NT-proBNP on admission. Mortality was 34.7%, 37.5%, and 58.8% for patients with low, borderline, and high NT-proBNP, respectively. Global mortality, re-hospitalization rate, ICU length of stay and duration of mechanical ventilation were similar among groups. In univariate analysis, patients with high NT-proBNP levels were at significantly higher risk for in-hospital mortality [(HR) 3.60, 95% CI 1.36–9.55, p = 0.010]; in patients with low and borderline levels mortality was not different. In multivariate Cox regression, after adjusting for significant confounders, patients with high NT-proBNP levels remained at significantly higher risk for in-hospital mortality [(HR) 3.44, 95% CI 1.07–10.1, p = 0.039] compared with the lower NT-proBNP groups. No significant differences were found between groups with low and borderline NT-proBNP. Kaplan-Meier survival curves are presented in figure 1. Conclusion(s) In critically ill patients with COVID-19, high admission NT-proBNP is associated with higher ICU mortality. Preventive strategies may be required for these patients. Studies with a larger population are required to draw further conclusions.

Funding Acknowledgements Type of funding sources: None. Background INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles provide important prognostic information for patients with advanced heart failure (AHF) hospitalized for clinical worsening. Purpose Assess the prognosis and fate of patients with Advanced HF (AHF), in INTERMACS I-IV, admitted to an Advanced Heart Failure Unit during 10-years. Methods Retrospective, single-center study with AHF’ patients admitted for acute HF during January 2010 and December 2020 in an Advanced Heart Failure Care Unit (AHFCU), who required inotropic therapy (INTERMACS I-IV) and were candidates for heart transplant ( Results For 10 years, 175 patients who met the inclusion criteria were admitted to the AHFC, mostly men (66.2%) and ischemic (30%), with a mean age of 52±10 years. At admission the patients had a mean Left Ventricle Ejection Fraction (LVEF) of 27±10% and a median NT-proBNP of 7230 pg/ml (IQR 3801 to 19882). During the 10-years on focus, 42% patients were transplanted (n=73), 38% (n=66) remained alive with optimized MT and device and 20% (n= 36) died. In-hospital mortality was significant different between profiles (p=0.001), 55% in INTERMACS I patients, 25% in II, and 17% in III-IV. Most transplanted patients (63%) were in INTERMACS IV, 16.4% in III, 12.3% in II and only 11% (n=8) in INTERMACS I (p=0.043). Conclusion Our results reinforce the importance of early action in these patients, using INTERMACS profile to prognostic stratification, who is important to identify the ideal time for referral to an appropriate centre, to properly convey expectations to patients and families, and to plan treatment and follow-up strategies (transplant, circulatory mechanical support, or palliative care).

Funding Acknowledgements Type of funding sources: None. Background/Introduction Among patients with COVID-19, there is a high prevalence of cardiovascular disease and myocardial injury from the infection, especially in critically ill patients. Purpose This study sought to investigate the relationship between elevated admission high-sensitive troponin I in COVID-19 patients admitted to an intensive care unit (ICU) and prognosis. Methods We retrospectively analyzed patients consecutively admitted to an ICU with COVID-19, with a median follow-up of 10 months. Patients who were diagnosed with acute coronary syndrome, either died or were discharged within 48 hours of admission, and who did not have a cardiac troponin measurement in the first 48 hours, were excluded. Two groups were identified, with normal troponin and with elevated troponin. Groups were compared, with special interest regarding in-hospital mortality, duration of mechanical ventilation, in-hospital diagnosis of heart failure, and length of hospitalization. Global mortality (in-hospital and during follow up) and re-hospitalization were compared. To compare survival, a Kaplan-Meier curve with log rank test was performed. Results From a total of 219 patients, after applying the exclusion criteria, 100 patients were included in the analysis, mean age was 62.9 ±12.5 years, and 74% were male. Troponin was normal in 77% of patients and elevated in 23%. Median troponin was 11 (IQR=26) ng/L (reference range Patients with elevated troponin were older (66.5 ±12.0 vs 61.6 ±12.5 years, p=0.036). Gender, comorbidities, vasopressor use, and APACHE II score were similar among groups. Patients with elevated troponin presented a higher ICU mortality (16.9% vs 47.8%, p=0.002) and higher global mortality (22.1% vs 47.8%, p=0.016). Re-hospitalization rates, ICU length of stay and duration of mechanical ventilation were similar among groups. In multivariate analysis, after adjustment for age and APACHE II score, an elevated troponin remained an independent predictor of ICU mortality (OR=3.40, 95% CI 1.08-10.4, p=0.036), but not an independent predictor of global mortality (OR=2.75, 95% CI 0.86-8.80, p=0.087). Kaplan-Meier analysis (Figures 1 and 2) showed that patients with elevated troponin had higher ICU (p=0.008) and global mortality (p=0.008) when compared to patients with normal admission troponin. Conclusion(s) The present study shows that elevated high-sensitive cardiac troponin I at admission predicts ICU and global mortality in critically ill COVID-19 patients. Cardiac troponin is as easy-to-use tool that may help to identify patients who benefit from tighter monitoring both during hospitalization and after discharge.

Funding Acknowledgements Type of funding sources: None. Background/Introduction The association between new-onset atrial fibrillation (AF) and prognosis in critically ill non-COVID-19 patients and non-critically ill patients has been studied, but few studies reflect the reality of COVID-19 patients admitted to a general intensive care unit (ICU). Purpose This study sought to investigate the relationship between new-onset AF in COVID-19 patients admitted to an ICU and prognosis. Methods We retrospectively analyzed patients consecutively admitted to an ICU with COVID-19, with a median follow-up of 10 months. Two groups were identified, with new-onset AF and without new-onset AF. Groups were compared, with special interest regarding ICU mortality, duration of mechanical ventilation, in-hospital diagnosis of heart failure, NT-proBNP value in the first 48 hours after admission, and length of hospitalization. Mortality rate and re-hospitalization during follow-up were compared. Results From a total of 219 patients, AF was identified in 17.8% (n=39) of patients, of whom 69.2% (n=27) presented new-onset AF. Patients with new-onset AF were older (66.4 ±9.0 vs 61.5 ±12.2, p In multivariate logistic regression, after adjustment for age and APACHE II score, new-onset AF was identified as an independent predictor of ICU mortality (OR=2.475, 95% CI 1.05-5.84, p=0.039). Conclusion(s) The present study shows that new-onset AF in critically ill patients is not a trivial phenomenon and is closely related to the risk of death and worse in-hospital outcomes.

Funding Acknowledgements Type of funding sources: None. Background In patients with acute coronary syndrome (ACS) the acute phase reactant, C-reactive protein (CRP), might be significantly elevated. Several reports suggest that CRP may play a direct pathophysiological role on the development and progression of atherosclerosis, and CRP values correlate with infarct size when measured by magnetic resonance imaging. Purpose The aim of the present study was to evaluate the prognostic value of CRP in patients presenting with an ACS. Methods Retrospective analysis of 635 consecutively admitted patients due to ACS in a single coronary intensive care unit. CRP levels were measured at admission. Clinical variables and therapeutic strategies were examined. The primary endpoint analysed during follow-up was all-cause mortality. Possible predictors for all-cause mortality were assessed by Cox regression models. When statistically significant values were found in univariate analysis, multivariate analysis was used to determine whether CRP was an independent predictor of outcome. Results In the studied sample, 75% were male. Median age was 69 [interquartile range (IQR) 57–78]. ST-elevation myocardial infarction (STEMI) occurred in 39.6%, non-ST segment elevation myocardial infarction in 44.9% and unstable angina in 15.5% of the patients. Median left ventricular ejection fraction (LVEF) was 48% (IQR 40–55%) and median CRP level at admission 0.7 mg/dL (IQR 0.5–1.9 mg/dL). Regarding important comorbidities and past medical history, 75.9% had hypertension (HTN), 34.0% diabetes, 20.3% chronic kidney disease (CKD), 68.6% dyslipidaemia and 17.3% heart failure (HF). The median follow-up was 34 months (IQR 22–72). In univariate analysis, CRP was significantly associated with all-cause mortality (HR 1.06 per 1 mg/dL increase, 95% CI 1.04–1.08, p Conclusions In our study, CRP at admission was an independent risk factor for all-cause mortality following an ACS. This finding indicates that inflammation associated with the acute event has a significant impact in the long-term prognosis. More evidence is needed to determine if treating inflammation (and when, in the course of the disease) could result in better outcomes.

Funding Acknowledgements Type of funding sources: None. Background After an ST-elevation myocardial infarction (STEMI), the risk of subsequent cardiovascular events is high. Risk stratification at index hospitalization remains a core challenge, especially in patients with subtle changes in LV function. Early systolic lengthening (ESL) may occur in ischemic myocardial segments with reduced contractile force and it has been correlated with infarct size and prognosis in STEMI patients with mildly impaired LV function. In this study, we aimed to evaluate the correlation of ESL with common echocardiographic parameters and its prognostic value in STEMI patients with preserved LV function. Methods We retrospectively included all the patients admitted to an intensive care unit with STEMI and a left ventricle ejection fraction ≥55% from January to June of 2016. Patients with inadequate image quality for speckle tracking echocardiographic examination were excluded (n = 14). We evaluated the ESL index, defined as follows: [−100×(peak positive systolic strain/peak negative strain in cardiac cycle)], and ESL duration. Results A total of 37 patients were included in the study. Mean age was 63 ± 12 years with a male preponderance (81%). All patients were submitted to complete revascularization. Median values of the ESL index and ESL duration were 7% (IQR, 4%–10%) and 37 msec (IQR, 21–55 msec), respectively. No significant differences were found between ESL index and ESL duration groups, except for a higher prevalence of heart failure at hospitalization in both highest groups, and women were more prevalent in the ESL index higher group (Tables 1 and 2). ESL index was correlated with post-systolic index (PSI) (r2 = 0.34, p = 0.04) and showed a weak correlation with E/A ratio (r2=-0.37, p = 0.02). ESL duration was correlated with ESL index (r2 = 0.76, p Conclusions In our cohort of STEMI patients with preserved LV function, assessment of ESL yielded important and significant prognostic information on MACE. ESL may be a useful tool to enhance routine risk stratification in this population. Abstract TABLE 1 Abstract TABLE 2

Introduction Catheter ablation has become the first-line treatment for symptomatic patients with atrial fibrillation (AF). Several approaches of substrate ablation have been used for persistent and long-standing persistent AF and the best protocol procedure is yet to be established. The purpose of this study was to evaluate the outcomes of patients submitted to catheter ablation of persistent and long-standing persistent AF adding extra-pulmonary substrate approaches to pulmonary vein isolation. Methods We retrospectively studied 67 consecutive patients referred for the first procedure of catheter ablation of persistent or long-standing persistent AF from May 2016 to October 2018. The first 27 patients were subjected to pulmonary vein isolation and complex fractionated atrial electrograms (CFAE) ablation (group 1) and the last 40 patients were subjected to a tailored approach guided by voltage map areas and CFAE (group 2). Patient characteristics, procedure details and follow-up were assessed, and predictors of recurrence were determined. Results Mean age was 59±11 years with 58% being male. During a mean follow-up of 16±6 months 27% of the patients showed AF recurrence. There were no differences in baseline characteristics of group 1 and 2. A higher recurrence rate was found in group 1 by comparison with group 2 (40.7% vs 17.5%, Log Rank X2 = 5.076, P=0.024) (Figure 1). Also, recurrence was associated with a longer AF duration, an increased baseline Brain Natriuretic Peptide (BNP), an increased left atrium (LA) volume, the presence of hyperthyroidism, the absence of sinus rhythm after procedure, the inducibility of AF post-ablation and the absence of an antiarrhythmic drug at hospital discharge. After adjustment for other confounders, the patient group (HR 5.16 [1.23–21.71] P=0.025), a long-standing AF (HR 9.09 [1.41–58.82] P=0.020), the BNP value at admission (HR 1.03 [1.01–1.05] P=0.033) and the LA volume index (HR 1.13 [1.02–1.25] P=0.017) were the only independent predictors of recurrence. Conclusion Ablation of persistent and long-standing persistent AF is feasible with good results when a substrate approach is added to pulmonary vein isolation. A tailored approach seems to be more efficient, showing best outcomes in mid-term follow-up. A long-standing AF, higher BNP value and the LA enlargement are important predictors of recurrence and should be used to better select patients and to manage follow-up. Funding Acknowledgement Type of funding sources: None.

Background Cardiopulmonary exercise testing (CPET) has an important role in mortality prediction in heart failure (HF) and patient selection for heart transplant. New indices as circulatory power (CP) and ventilatory power (VP) have been proposed as predictors of cardiac events. In addition, VP predicts mean pulmonary artery pressure (mPAP) in patients with pulmonary arterial hypertension. Purpose We aimed to analyse the prognostic value of classic and new CPET variables in patients with HF. Methods We retrospectively assessed consecutive patients with HF who underwent CPET in a single-centre between 2013 and 2017. New CPET variables were collected: CP was defined as the product of peak O2 uptake and peak systolic blood pressure (SBP), while VP was defined as peak SBP divided by the minute ventilation–CO2 production (VE/VCO2) slope. The primary endpoint was a composite of all-cause mortality, heart transplant, or HF hospitalization. Survival analysis was performed using Kaplan-Meier curves and multivariable Cox regression. Results Overall, 216 patients (mean age 55.4±10.9, 77.3% male) were included, 38.4% with ischemic HF, and mean left ventricle ejection fraction (LVEF) 30±14%. Most patients were evaluated through the modified Naughton (76.3%), the original Naughton (19.0%), and Bruce protocols (4.7%). Regarding classic CPET variables: mean pVO2 16.8±6.0 mL O2 kg–1 min–1, mean percent-predicted pVO2 62.6±23.9%, median VE/VCO2 slope 37.3 [32.6–44.5], exercise oscillatory ventilation (EOV) present in 13.9%, resting partial pressure of end-tidal carbon dioxide (PETCO2) ≥33 mmHg with an increase of 3–8 mmhg during exercise in 17.1%, and mean peak SBP 128.8±27.2 mmHg. Median circulatory power was 1927 [1404–2694] mmHg·min/mL/kg and mean ventilatory power 3.47±1.32 mmHg. After a median follow-up of 5 [4–6] years, the primary endpoint occurred in 66.2% of patients (rehospitalization, heart transplant, and all-cause death occurred in 57.0%, 25.9%, and 32.4%, respectively). In Cox regression multivariate analysis, the primary endpoint was predicted by pVO2 (HR 0.90, 95% CI: 0.87–0.93), percent-predicted pVO2 (HR 0.97, 95% CI: 0.96–0.98), VE/VCO2 slope (HR 1.04, 95% CI: 1.03–1.06), VP (HR 0.62, 95% CI: 0.52–0.73) but not CP (HR 0.99, 95% CI: 0.98–1.01). Kaplan-Meier curves according to the LVEF are depicted in Fig. 1A. ROC analysis (Fig. 1B) revealed that VP (AUC 0.768) has higher discriminative power for the primary endpoint, compared to pVO2 (AUC 0.741). One hundred and twenty-seven patients also underwent right heart catheterization: mean mPAP was 30.6±12.9 and it was not correlated with VP (r=−0.06, p=0.47). Conclusion CPET variables are good predictors of all-cause mortality, heart transplant, or HF hospitalization. Ventilatory power (but not circulatory power) is an additional useful variable in event prediction. On the other hand, VP is not correlated with mPAP in patients with HF. Funding Acknowledgement Type of funding sources: None.

Introduction Cardiopulmonary exercise testing (CPET) is routinely used in the prognostic evaluation of patients with heart failure with reduced ejection fraction (HFrEF). Left ventricular ejection fraction (LVEF) is a strong prognostic marker but have shown a bad correlation with exercise capacity. The aim of this study is to assess the relationship between echocardiographic parameters and exercise capacity in HFrEF patients. Methods We retrospectively assessed all patients with HFrEF submitted to CPET and echocardiography between March and September of 2019. 73 patients were eligible for analysis. ANOVA test was used to compare Weber class groups regarding echocardiographic parameters. Multivariate linear regression with a stepwise approach was used to assess independent predictors of peak VO2 uptake. ROC curves were compared to assess the best parameter to discriminate a peak VO2 Results Mean age was 53.4±11.7 years with 72.6% being male. Mean LVEF was 29.2±7.7% and mean peak VO2 was 13.4±3.8 ml/kg/min. Between the Weber class groups, significant differences were found in left (LV) and right ventricular (RV) longitudinal strain (P Conclusion RV longitudinal strain and TRmax seem to be the best echocardiographic predictors of exercise intolerance in patients with HFrEF. Since CPET is not widely available, these echocardiographic parameters can be clinically useful as a surrogate prognostic factor. Funding Acknowledgement Type of funding sources: None.

Background Bisphosphonates (BPs) are widely prescribed drugs that decrease bone fracture risk in osteoporosis patients. Nevertheless, the class has been associated with a plethora of adverse effects, including incidental atrial fibrillation (AF). This epidemiologic link has, however, been met with skepticism by some authors. Purpose To perform a meta-analysis aimed at ascertaining the extent to which BPs might increase the odds of AF. Methods We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library and Google Scholar, from inception to the first of March, 2021, for randomized controlled trials comparing oral or intravenous BPs with placebo or a no-treatment control, in what concerns AF risk. In order to be included in the quantitative analysis, studies were required to feature a minimum patient follow-up of 6 months. De novo AF diagnoses served as the primary endpoint. Data related to individual BPs were further investigated separately, with respect to this outcome. Study-specific Mantel-Haenszel odds ratios (ORs) were pooled using traditional meta-analytic techniques, under a random-effects model. Results 42 RCTs, encompassing 52.436 patients (32.071 randomized to BPs), were regarded as eligible for quantitative synthesis. Of note, 2 pooled analyses, one of 4 trials with ibandronate and the other of 6 trials with risedronate, were included. Individual BP representation may be depicted as follows: Alendronate, 23 trials, with 14.599 patients; Risedronate, 7 trials, with 15.350 patients; Zoledronic acid, 7 trials, with 13.059 patients; Ibandronate, 4 trials, with 8.754 patients; and Minedronate, 1 trial, with 674 patients. 748 de novo AF diagnoses were reported, in total. In the main analysis, BPs were not found to be significantly associated with an increase in AF odds (OR 1.10, 95% CI 0.95–1.28, P 0.21, i2 0%). As for individual BPs, Alendronate (OR 1.09, 95% CI 0.82–1.45, P 0.55, i2 0%), Risedronate (OR 0.81, 95% CI 0.35–1.86, P 0.61, i2 31%), Ibandronate (OR 0.89, 95% CI 0.52–1.52, P 0.67) and Minedronate (0 AF events reported, both in the active and in the control group) were also not shown to meaningfully enhance AF risk. On the contrary, Zoledronic acid utilization was associated with a significant, though small, increase in new AF cases (OR 1.29, 95% CI 1.01–1.64, P 0.04, i2 0%). Conclusion The professed BP-driven increase in AF odds is not apparent in a fairly populated randomized setting. In fact, a barely significant increment in AF risk seems only to occur with the most potent BP (Zoledronic acid). Therefore, AF development concerns should not refrain doctors from prescribing this highly effective pharmacological class. Funding Acknowledgement Type of funding sources: None.

Background Pulmonary hypertension (PH) is a clinical syndrome characterized by an increase in pulmonary artery pressure. Among the five groups of PH, pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) stand out due to their ominous prognosis without specific treatment. However, very long-term outcomes data are scarce. Purpose We aimed to assess the very long-term survival of PAH and CTEPH patients followed in a Portuguese PH referral center. Methods Between January 2009 and January of 2020, all incident PH cases were consecutively enrolled in a prospective cohort study. A total of 177 patients were followed up for a median of 5.0 [interquartile range 2.3–8.7] years. Kaplan-Meier survival analysis was used to estimate 1-, 5- and 9-year survival and multivariate regression was used to predict independent prognostic factors. Results Mean age was 49±20 years with a clear female preponderance (67%). The most common PH subgroups were congenital heart disease (PAH-CHD) (n=62; 35%), followed by CTEPH (n=52; 29,4%), connective tissue disease (PAH-CTD) (n=31; 17.5%), idiopathic/hereditary PAH (I/HPAH (n=22; 12.4%) and portopulmonary hypertension (PoPH) (n=8; 4.5%) (Table 1). PAH-specific drugs were used in 91% of the patients, dual combination therapy in 47.5%, and triple combination in 12.4%. The remaining 9% successfully received non-pharmacological treatment, namely cardiac surgery in PAH-CHD (n=7) and endarterectomy or angioplasty in CTEPH (n=9). Survival rates at 1-, 5- and 9-years were 97%, 80% and 66%, respectively. Age (hazard ratio [HR] 1.02; 95% CI 1.01–1.04; P=0.049), BNP [HR 2.04 (1.16–3.60); P=0.01], admission for decompensation of heart failure (HF) [HR 3.15 (1.71–5.83); P Conclusions In this cohort of incident PH patients, the overall 9-year survival rate was 66%. PAH-CHD patients had better overall prognosis, while patients with PAH-CTD and PoPH had the worst prognosis. Additionally, older age, higher BNP and admission for HF were associated with higher mortality. Funding Acknowledgement Type of funding sources: None.

Background Compared with the cardiac exercise stress test, more commonly used to assess the presence of ischemia, the cardiopulmonary exercise test has the advantage of providing expired gas analysis. According to current guidelines, cardiopulmonary exercise testing should be considered to stratify the risk of adverse events and to provide measures of survival improvement in heart failure populations. However, cardiac exercise stress test is more readily available and widespread than cardiopulmonary exercise testing. We aimed to compare prognostic information given by estimated pVO2 – which can be obtained from cardiac exercise stress test – and real measured pVO2 – which requires cardiopulmonary exercise test – in a heart failure population. Methods We conducted a retrospective analysis of 214 patients with HF underwent cardiac exercise stress test and accessed their 5 year survival. Non-urgent transplanted (UNOS Status 2) patients were censored alive on the date of the transplant. Duringthe cardiopulmonary exercise test, cardiac exercise stress test data simultaneously collected. Based on protocol stage achieved, estimated METs were used to calculate estimated pVO2 (pVO2 = estimated METs x 3.5). Estimated and real pVO2 were correlated using Pearson correlation and the age-adjusted prognostic power of each was determined using Cox proportional hazardsanalysis. Results 164 patients were male (77%) and the mean age of the population was 56±10 years. 78 (36%) patients had an ischemic etiology. Within 5 years from testing, 46 patients died (21.5%) and 55 patients (26%) were transplanted. Naughton modified (n=165) was the most commonly used protocol, followed by Naughton (n=39) and Bruce (n=10). Estimated pVO2 and measured pVO2 correlated significantly (R=0.66, p Conclusions Estimated pVO2 correlated with measured pVO2 and strongly predicted prognosis in this heart failure population. Because it can be obtained from conventional cardiac exercise testing, it may become an alternative prognostic tool to cardiopulmonary testing. Funding Acknowledgement Type of funding sources: None. Figure 1. Measured vs estimated pVO2

Background Idiopathic pulmonary arterial hypertension (iPAH) is a rare and chronic disease associated with poor outcomes. Previously considered a disease restricted to the pulmonary circulation, PAH is now being recognized as a systemic disorder that is associated with metabolic dysfunction. The aim of this study is to analyze the metabolic reprogramming in the lung and peripheral blood mononuclear cell (PBMCs) of iPAH patients and explore their potential roles in PAH pathophysiology. Methods Five independent datasets, containing transcriptomic data of human PBMCs (GSE22356 and GSE33463) and lung (GSE48149 GSE113439 and GSE117261) samples, from 139 iPAH patients and 96 healthy controls, were downloaded at the GEO database. In each dataset, the samples were normalized and a pair-wise comparison between control and iPAH samples was performed using limma package, for the R programming language. Genes with a p-value lower than 0.05 were considered differentially expressed between the two groups. A subset of metabolism related genes was selected, and their expression was compared across the datasets. Results Among the 13 genes with differential expression identified, only 10 had a coherent expression across all datasets (Figure 1). Firstly, we report an association with insulin resistance through impairment of PI3K signaling in iPAH patients, by expressing lower levels of the heterodimer PIK3CD and regulatory PIK3IP1 and PIKR1 subunits in PBMCs, and by expressing higher levels of its downstream targets in the lung (TBC1D4). However, more extensive metabolic dysfunction was observed. A significant glycolytic shift in the lung and PBMCs was present, as a consequence of deregulation in genes involved in aerobic glycolysis and decreased fatty acid oxidation, namely increased expression of PD1K and lower levels of expression of LDHB. The findings of decreased SLC25A1 protein in both PBMCs and lung suggest impairment of the tricarboxylic acid (TCA) cycle flux in PAH. Additionally, SLC1A5 highlights the involvement of glutamine metabolism and glutaminolysis derangements in PAH. Conversely, SREBP1 is involved in sterol biosynthesis and lower levels in PMBCs results in impaired resolution of inflammatory responses. Finally, although the role of autophagy in iPAH is complex, higher levels of expression of ATG13 in PBMCs and lower levels in the lung confirm autophagy deregulation in iPAH. Interestingly, all the metabolic pathways identified (Figure 2) are hallmarks of the metabolic reprogramming seen in cancer cells, a finding already suggested by the clonal proliferation of pulmonary artery smooth muscle cells described in plexiform lesions. Conclusion Our results provide novel insights into the metabolic regulation in iPAH. Molecularly, these cells exhibit many features common to cancer cells, suggesting the opportunity to exploit therapeutic strategies used in cancer to treat iPAH. Funding Acknowledgement Type of funding sources: None.

Background Although widely recommended for risk assessment of patients with acute coronary syndrome (ACS), the Global Registry of Acute Coronary Events (GRACE) score famously lacks discriminative power. On the other hand, in-hospital serum hemoglobin levels (HG) have been shown to simultaneously forecast both thrombotic and hemorrhagic hazards. Purpose To ascertain the extent to which the incorporation of HG in the GRACE score is able to increase its predictive ability. Methods Retrospective single-center study encompassing ACS patients consecutively admitted to a Cardiac Intensive Care Unit. Inclusion criteria comprised the acquaintance of GRACE score, HG and vital status on a 6-month follow-up, which served as the outcome. 3 discriminative models were first created: (standard) GRACE score (model 1); GRACE score plus HG, by means of logistic regression (model 2); GRACE score plus HG, by means of multilayer perceptron (a class of feedforward artificial neural network) (model 3). Hereafter, if models 2 and/or 3 were to be found significantly more discriminative than model 1, a correction factor would be calculated, also allowing for the conception of the most predictive model possible (model 4). The discriminative ability was estimated by both the area under the receiver-operating characteristic curve (AUC), and the dyad sensitivity/specificity. Results Between April 2009 and December 2016, 1468 patients met study inclusion criteria. Mean age was 68.0±13.2 years and 29.8% were female, while 36.9% presented with ST-segment elevation myocardial infarction. Mean GRACE score was 145.5±47.0 and mean HG was 13.5±2.0. All-cause mortality reached 10.5%, at 6 months. Predictive power for models 1, 2 and 3 may be quantified as follows: AUC 0.6998, sensitivity 77.7% and specificity 62.5%; AUC 0.7818, sensitivity 36.3% and specificity 92.2%; AUC 0.7851, sensitivity 47.7% and specificity 88.5%, respectively. Both models 2 and 3 exhibited more discriminative ability than model 1 (p Conclusion HG single-handedly provides incremental predictive value – namely more specificity – to the GRACE score. In particular, the latter seems to overestimate ACS patients' risk if HG is normal or close to normal. Funding Acknowledgement Type of funding sources: None.