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Background Cardiac sarcoidosis (CS) is clinically diagnosed in 5% of patients with sarcoidosis but imaging studies suggest higher prevalence. We evaluated the prevalence, clinical manifestations, and cardiovascular outcomes of CS, diagnosed through 18F-Fluorodeoxyglucose positron emission tomography ([18F]FDG-PET), in a southern European population. Methods Retrospective single-centre study of patients screened for sarcoidosis with [18F]FDG-PET. Subjects with histological confirmation were divided in two groups, CS or extracardiac sarcoidosis, according to Heart Rhythm Society's criteria. Primary endpoint was defined as the composite of heart failure hospitalizations, uncontrolled arrythmias, pacemaker implantation, and cardiovascular (CV) mortality. Secondary outcomes included each component and all-cause mortality. Results From 128 patients with biopsy-proven extracardiac sarcoidosis, 10.2% had probable CS, 54% without symptoms of cardiac involvement. Ten patients had suggestive [18F]FDG uptake patterns, three subjects had an indicative cardiac magnetic resonance (CMR). Patients with probable CS had significantly higher prevalence of coronary and valvular disease, heart failure, and atrial fibrillation compared with those without cardiac involvement. During a mean follow-up of 4.0 SD2.7 years, the primary outcome occurred more frequently in patients with probable CS (53.8% vs. 3.5%; HR 25.45; 95% CI 5.27–122.9; p Conclusions Among patients with biopsy-proven sarcoidosis, cardiac involvement detected by [18F]FDG-PET or CMR is associated with a higher risk of CV events, irrespective of symptoms.

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.

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.

Fluorine-18 sodium fluoride (Na[18F]F) atherosclerotic plaque uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification. We aim to evaluate global cardiac microcalcification activity with Na[18F]F, as a measure of unstable microcalcification burden, in high cardiovascular (CV) risk patients. Thirty-four high CV risk individuals without previous CV events were scanned with Na[18F]F PET-CT. Cardiac Na[18F]F uptake was assessed through the global molecular calcium score (GMCS), which was calculated by summing the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. Mean age is 63.5 ± 7.8 years and 62% male. Median GMCS is 320.9 (240.8-402.8). Individuals with more than five CV risk factors (50%) have increased GMCS [356.7 (321.0-409.6) vs. 261.1 (225.6-342.1), P = 0.01], which is positively correlated with predicted fatal CV risk by SCORE (rs = 0.32, P = 0.04). There is a positive correlation between GMCS and weight (rs = 0.61), body mass index (rs = 0.66), abdominal perimeter (rs = 0.74), thoracic fat volume (rs = 0.47), and epicardial adipose tissue (rs = 0.41), all with P ≤ 0.01. There is no correlation between GMCS and coronary calcium score nor coronary artery wall Na[18F]F uptake. In a high CV risk group, the global cardiac microcalcification burden is related to CV risk factors, metabolic syndrome variables and cardiac fat. Cardiac GMCS is a promising risk stratification tool, combining a straightforward and objective methodology with a comprehensive analysis of both coronary and valvular microcalcification.

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.

Funding Acknowledgements Type of funding sources: None. Background Overt cardiac involvement is reported in 5% of patients with sarcoidosis, although autopsy and imaging studies suggest higher prevalence, worldwide variation. The role of 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) in non-invasive diagnosis and follow-up has increased in the last decade. Purpose Our goal is to describe the prevalence, clinical manifestations and outcomes of cardiac sarcoidosis (CS), diagnosed through [18F]FDG-PET, in a southern European population. Methods We included all patients with histological diagnosis of extracardiac sarcoidosis screened with [18F]FDG-PET between 2009 and 2020. We collected data on clinical manifestations, cardiac magnetic resonance (CMR) results, and mortality outcomes and compared those with and without cardiac involvement. We applied the criteria for the diagnosis of CS from Heart Rhythm Society. Results Of the 400 patients screened with [18F]FDG-PET, 128 had a histological diagnosis of extracardiac sarcoidosis (54.7% females, mean age 51.0 ± 14.2 years). None underwent endomyocardial biopsy. Ten patients had a pattern of [18F]FDG uptake consistent with CS defined as diffuse (n = 5), focal (n = 3), and focal on diffuse (n = 2). Of the 128 patients, 14 also underwent CMR, which identified 2 subjects with positive findings in both modalities and 3 additional patients: focal (n = 1), multifocal mid-wall (n = 2), focal mid-wall (n = 2), and multifocal subepicardial (n = 1) delayed gadolinium enhancement. Overall, 13 patients (10.2%) fulfilled the criteria for probable CS (53.8% female, mean age 56.2 ± 12.6 years), all with multiorgan involvement, mostly lung and lymph nodes (each 92%), followed by skin and central nervous system (each 15%). Median left ventricle ejection fraction was 62% [55-65] and there were cardiac manifestations of CS in 6 patients (46%): sick sinus syndrome (n = 2), complete heart block (n = 1), frequent premature ventricular complexes (n = 1), ventricular tachycardia plus heart failure (n = 1), and bifascicular block plus heart failure (n = 1). Eleven patients (85%) with probable CS were medicated with immunosuppressant drugs: corticosteroids (n = 9), methotrexate (n = 4), and azathioprine (n = 2). Four patients with previous [18F]FDG screening were revaluated after treatment, each showing no cardiac uptake. After a mean follow-up of 4.0 ± 1.0 years, mortality was three-fold higher in patients with cardiac involvement, despite the absence of statistical significance (15% vs. 5%, P = 0.151). Conclusions In a southern European population with histological extracardiac sarcoidosis, the prevalence of cardiac involvement was 10.2%, most asymptomatic. [18F]FDG-PET improves the diagnostic yield and plays an important role in monitoring response to therapy. The higher mortality trend in those with CS needs to be ascertained in longer follow-up.

Funding Acknowledgements Type of funding sources: None. Introduction Calcification plays a major role in coronary atherogenesis. Positron emission tomography (PET) imaging with fluorine-18 sodium fluoride (Na[18F]F) is able to detect microcalcification and is associated with cardiovascular (CV) risk factors. Thoracic fat volume (TFV) and epicardial adipose tissue (EAT) are associated with atherosclerosis, pro-inflammatory state, and CV events. Purpose We aimed to evaluate the association between Na[18F]F uptake and cardiac fat variables. Methods Cardiac Na[18F]F uptake was assessed as global molecular calcification score (GMCS): the sum of the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. TFV was assessed in computed tomography (CT) using automated software to sum the voxels consisting of fat (threshold of -190 to -30 Hounsfield units) between the bifurcation of pulmonary artery and the end of pericardial sac. EAT was segmented manually tracing the counter of the pericardium with 3DSlicer and the final volume calculated using the dedicated software. Coronary artery calcium score (CAC) was measured with dedicated software for calcium scoring (GE Healthcare Advantage Workstation 4.2). Results Thirty-four high CV risk individuals without previous CV events (50% with ≥5 CV risk factors) were retrospectively scanned with Na[18F]F PET-CT. Mean age is 63.5 ± 7.8 years and 62% male. Median values are: GMCS 320.9 (240.8-402.8), TFV 167.8 (131.4-211.3) mL, EAT 81.3 (60.7-107.2) cm3, and CAC 0.0 (2.5-20.0). There is a positive correlation between GMCS and abdominal perimeter (rs = 0.74), weight (rs = 0.61), TFV (rs = 0.47), and EAT (rs = 0.41), all with p ≤ 0.01. Thoracic and epicardial fat volumes are strongly correlated (rs = 0.80, p Conclusions In this exploratory analysis with high CV risk patients, the global cardiac microcalcification burden assessed by GMCS is associated with TFV and EAT, but there was no correlation between these variables and CAC. We hypothesize that both GMCS and cardiac fat variables might help to identify higher-risk patients in earlier phases than traditional CT.

Funding Acknowledgements Type of funding sources: None. Introduction The blood urea nitrogen-to-creatinine ratio (BUN/SCr) has been proposed as a prognostic marker in heart failure (HF). We aimed to evaluate whether BUN/SCr predicts mortality outcomes in a real-world Southern European population with decompensated chronic HF. Methods We retrospectively studied 1057 patients with chronic HF admitted to our emergency department between November 2016 and December 2017 with acute decompensation. We excluded patients with a GFR Results 1025 patients were included, median age 80 years (IQR 73-85), 52.4% male, mean LVEF 42.8 ± 12.7%, and mean GFR 57.2 ± 23.9 mL/min/m2. Mean BUN/SCr was 24.9 ± 8.2 and mean SBP was 139 ± 29mmHg (r=-0.17, p 27.15). In the T3 group, the multivariable-adjusted OR for CV and all-cause death was 5.43 (95% CI 2.20-13.37) and 2.72 (95% CI 1.66-4.46), respectively, compared to the T1 group. No significant differences between T1 and T2 groups. Conclusions BUN/SCr at admission predicts CV and all-cause death in patients with chronic HF after an episode of decompensation. BUN/SCr, as an easy-to-use tool, helps to identify those patients who benefit from tight monitoring both during hospitalization and after discharge. Abstract Figure_1

Funding Acknowledgements Type of funding sources: None. Background Elevated plasma lipoprotein(a) [Lp(a)] concentrations are associated with an increased risk of atherosclerotic cardiovascular disease and its role in risk categorizing was recognized in the new ESC guidelines for the management of dyslipidaemias. We investigated 1) the association between baseline Lp(a) levels and incident long-term cardiovascular (CV) events and 2) its relationship with type 2 diabetes mellitus (T2DM) in a Southern European population. Methods We retrospectively assessed baseline Lp(a) concentrations in a total of 499 patients of a primary prevention cohort followed at the Lipidology Clinic of our hospital, with a median follow-up time of 15 (IQR 12-17) years. Lp(a) was analysed as a continuous variable, as a categorical variable with a 180mg/dL cut-off and by quartiles. We collected data on major CV events (CV death, myocardial infarction, stroke) as a composite outcome. Cox proportional hazard regression analyses were used to estimate hazard ratios (HR) and 95% confidence interval (CI). Results Mean age was 48.30 ± 14.41 years and 61.70% were male (n = 499). Median Lp(a) was 36.60 (IQR 0-396) mg/dL and 12.4% of patients had very high Lp(a) (≥180mg/dL); T2DM prevalence was 13.60%. The composite outcome incidence was 10%. At the baseline, individuals with T2DM had lower Lp(a) levels (11.85 IQR 3-330 mg/dL vs. 46.40 IQR 0-396, p Conclusion In a single centre cohort of a primary prevention southern European population, we did not find an association between Lp(a) levels and incident CV events in a 15-year median follow-up time.

Funding Acknowledgements Type of funding sources: None. Introduction The incidence of acute myocardial infarction (AMI) among young patients is increasing. The YOUNG-MI Registry reported that those under 40 years had similar risk profiles and outcomes compared to those aged 41 to 50. We aimed to evaluate cardiovascular risk factors and mortality outcomes in two age cohorts from southern European. Methods We retrospectively evaluated 4758 patients admitted to our coronary intensive care unit between 2004 and 2017 with AMI. We only included patients Results From the 1233 patients included (mean age 50.5 ± 6.5 years, 82.2% male), 53% had STEMI. Cohort B had higher rates of hypertension (59.8 vs. 42.9%, p Conclusion Among patients who suffer AMI, those under 50 years old have a different risk profile, compared to the 50-60 years cohort. However, there is no significant difference in all-cause mortality. Abstract Figure.

Introduction The TIMI (Thrombolysis in Myocardial Infarction) and GRACE (Global Registry of Acute Coronary Events) risk scores identify high-risk patients with Non-ST elevation acute coronary syndrome (NSTE-ACS) who can benefit from an early invasive strategy. Purpose We aimed to compare both scores predictive accuracy for mortality in a real-world cohort of patients presenting with NSTE-ACS. Methods We retrospectively evaluated 4264 patients admitted to our coronary intensive care unit between 2004 and 2017 with a diagnosis of NSTE-ACS. The TIMI and GRACE scores were calculated for each patient, and all-cause mortality was recorded during hospitalization, at one month and one year. To better characterize global troponin release, we defined Total Troponin (TT) as the sum of initial and discharge troponin. We used the area under the receiver operating characteristic curve (AUC) to compare the predictive value of both scores for mortality during hospitalization, at one month and one year. Results Mean patient age was 67.6±12.4 years and 66.4% were male (n=2833). Mean GRACE score was 124.6±35.8 and mean TIMI score was 2.7±1.6. There was a weak correlation between GRACE and TIMI score (r=0.3, p Conclusion In patients with NSTE-ACS, GRACE risk score is a better predictor of in-hospital, one month and one-year mortality, compared to TIMI risk score. TT, as a measure of ischemia burden, might improve accuracy of GRACE score in predicting short and long-term mortality. Figure 1 Funding Acknowledgement Type of funding source: None

Introduction The expected delay of transport between patient location and percutaneous coronary intervention (PCI) centre is paramount for choosing the adequate reperfusion therapy in ST-segment elevation myocardial infarction (STEMI). The central region of Portugal has heterogeneity in PCI assess due to geographical reasons. However, this data is usually presented numerically without providing a visual distribution of patients. Purpose We aimed to analyse the impact of distance to PCI centres on mortality in patients with STEMI through visual maps of patients' flow by using an experimental process mining tool, integrated in EIT Health's project PATHWAYS. Methods Using the Portuguese Registry of Acute Coronary Syndromes (ProACS), we retrospectively assessed patients with an established diagnosis of STEMI, geographical presentation specified, reperfusion option identified (PCI, fibrinolysis or no reperfusion), short-term outcomes defined as discharge or in-hospital death. With the 2 317 patients that fulfilled the criteria, we used a process mining tool to build national and regional models that represent the flow of patients in a healthcare system, enhancing differences between groups. Results Colour gradient in nodes and arrows changes from green to red, with green representing a lower number of patients as opposed to red. In the national model, most patients from all regions had PCI. Mortality was similar between PCI and fibrinolysis groups (4%) but higher in those without reperfusion (9%). In the central region model, one third of the patients were more than 120 minutes away from a PCI centre. Despite that, almost one third of these patients had PCI instead of fibrinolysis. In this model, fibrinolytic therapy had higher in-hospital survival rate than PCI (98% vs. 94%). Overall mortality was higher in the central model compared with the national model (6.92% vs. 5%). Central region had less PCI (53% vs. 73%), more fibrinolysis (15% vs. 7%) and more patients with no reperfusion (32% vs. 20%). Conclusion In the ProACS registry, mortality was higher in the central region compared with national data. Even though global interpretation of these findings is limited by underrepresentation from certain central areas, process mining offers an easily understandable view of patients flow. With its statistical upgrade and continuous development, this tool will facilitate the analysis of big data and comparison between groups. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): EIT Health