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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 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.

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.

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.

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 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.

Introduction Cardiovascular diseases are the leading cause of death worldwide and the pandemic caused by coronavirus disease 2019 (COVID-19) has forced profound changes in the care of patients with cardiac conditions. In Portugal, an increase in mortality beyond that attributed solely to COVID-19 was observed. We aimed to realize how COVID-19 has changed the activity of our Interventional Cardiology Unit. Methods We retrospectively assessed all patients submitted to any interventional procedure in 2019 and 2020 in our hospital. A total of 7621 patients and 9163 procedures were evaluated. The mean weekly numbers of coronarography, angioplasty, right heart catheterization and structural heart intervention during 2019 were assessed and were compared with the first COVID-19 wave (comprising March and April 2020) and the second COVID-19 wave (including the time period from October to end of December 2020). Results Mean age was 65.2±16.6 years with 72% being male. In the first COVID-19 wave there was a significant reduction in the mean weekly numbers of all procedures, with a 64% decline in coronarographies (30.9±29.3 vs 87.2±12.9, P Conclusions In our Interventional Cardiology Unit, COVID-19 led to a significant reduction of procedures in the first and second pandemic waves. The effect on the increase in morbidity and mortality has yet to be determined. Health authorities should focus attention in defining measures to amend the consequences of this documented activity reduction. Funding Acknowledgement Type of funding sources: None. Figure 1

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 Ischemic stroke is a leading cause of death and disability in the Western world, frequently due to cardioembolism and atherothromboembolism. Cryptogenic strokes occur without a well-defined aetiology after a standard vascular and cardiac evaluation, and secondary prevention may include antiplatelet therapy while awaiting results of long-term cardiac monitoring. In this study, we aimed to identify echocardiographic predictors of paroxysmal atrial fibrillation (AF) latter identified in follow-up of patients with cryptogenic stroke. Methods We retrospectively assessed all patients with cryptogenic stroke admitted in our hospital in the last 2 years. Only patients in normal sinus rhythm with a minimum of 24 hours of cardiac monitoring at admission and 24 hours Holter monitor within 6 months after discharge were included. Echocardiographic measures included left ventricle ejection fraction, left atrium (LA) volume, left and right atrium longitudinal strain, left and right ventricle longitudinal strain, E/A ratio, E/e' ratio, isovolumetric relaxation time (IVRT) and E wave deacceleration time. Echocardiographic data was assessed to determine its accuracy to identify AF. Results The study included 32 patients with a mean age of 72±10 years and a male preponderance (87.5%). AF was identified in 12 (37.5%) patients. This group of patients had a larger indexed LA volume (44.3 vs 29.1 mL/m2, p=0.043), a lower IVRT (87 vs 116 ms, p=0.028), and a lower LA longitudinal strain in contractile (6.7 vs 13.6%, p Conclusion LA longitudinal strain in contractile phase is a powerful method to identify AF in cryptogenic stroke. When reduced, anticoagulation may be considered in order to prevent recurrence. Further studies are warranted to reproduce these results in larger cohorts. Funding Acknowledgement Type of funding source: None

The kepler and TESS missions have generated over 100,000 potential transit signals that must be processed in order to create a catalog of planet candidates. During the last few years, there has been a growing interest in using machine learning to analyze these data in search of new exoplanets. Different from the existing machine learning works, ExoMiner, the proposed deep learning classifier in this work, mimics how domain experts examine diagnostic tests to vet a transit signal. ExoMiner is a highly accurate, explainable, and robust classifier that 1) allows us to validate 301 new exoplanets from the MAST Kepler Archive and 2) is general enough to be applied across missions such as the on-going TESS mission. We perform an extensive experimental study to verify that ExoMiner is more reliable and accurate than the existing transit signal classifiers in terms of different classification and ranking metrics. For example, for a fixed precision value of 99%, ExoMiner retrieves 93.6% of all exoplanets in the test set (i.e., recall=0.936) while this rate is 76.3% for the best existing classifier. Furthermore, the modular design of ExoMiner favors its explainability. We introduce a simple explainability framework that provides experts with feedback on why ExoMiner classifies a transit signal into a specific class label (e.g., planet candidate or not planet candidate)., Comment: Accepted for Publication in Astrophysical Journals, November 12, 2021

Introduction Infective endocarditis (IE) remains a diagnostic and therapeutic challenge and is still associated with high mortality. Systemic complications are frequently present, and an adequate assessment and management are needed. Purpose Our aim is to show the importance of an early recognition of IE complications. Clinical case We present a case of 54 years old women with a past medical history unremarkable. The patient presented to the hospital with high fever and was admitted with a diagnosis of a psoas abscess and staphilococus aureus bacteremia. After one week of antibiotic treatment the patient was transferred to an intensive care unit due to septic shock and respiratory failure. The patient needed to be intubated and ventilated and was on treatment with vancomycin and meropenem. During admission, several infectious loci were identified, including cerebral and pulmonar involvement. An echocardiography identified mild mitral regurgitation, moderate tricuspid regurgitation and confirmed the presence of two vegetations, one in tricuspid valve with 30mm and one in mitral valve with 5mm. Nevertheless, the patient improved clinically. After 15 days of treatment, the patient was extubated and was transferred to the cardiology ward for follow-up. Although clinically stable and without any complain, repeated echocardiographic evaluation identified left ventricular apical aneurysm and partial resolution of vegetations. A coronariography was performed and did not identified any coronary lesion. A magnetic resonance confirmed the ischemic aetiology of the lesions and a diagnosis of embolic myocardial infarction was made. Considering a good resolution of infection, and being the patient stable and asymptomatic, she was discharged after 6 weeks of antibiotic therapy for follow up in cardiology and neurosurgery consultations. Discussion and conclusion Despite appropriate antimicrobial treatment, embolic complications are common and usually develop during initial stage of IE. This case shows several embolic complications of IE, including embolic myocardial infarction and cerebral embolism. Although aggressive antibiotic administration was successful in this particular case and cardiac surgery was avoided, the identification of complications allowed a more strict follow up and was determinant for a good clinical result. Abstract P1249 Figure.

BACKGROUND Left atrial (LA) mechanics is impaired in mitral valve disease, but it is not clear whether reservoir, conduit or contractile functions are differentially impaired in stenosis (MS) or regurgitation (MR). We aimed to study LA mechanics in patients with moderate MR or moderate MS and identify discriminators of disease. METHODS We conducted a prospective, observational study of 100 patients with isolated moderate MR and 100 patients with moderate MS. LA mechanics with speckle tracking echocardiography (STE) assessed LA reservoir (LA ɛsys and SRs), conduit(LAɛe, SRe), and contractile (LAɛa, SRa) functions. Left ventricle (LV) functional parameters were assessed as well, including LV ejection fraction (LVEF), LV end-diastolic diameter (LVDD) and LV global longitudinal strain (LV-GLS). RESULTS The mean age was 67 ± 14 years and 75% were female. Mean left ventricular ejection fraction (LVEF), LV end-diastolic diameter (LVDD), LV global longitudinal strain (LV-GLS) and systolic pulmonary artery pressure (sPAP) did not differ between MR and MS (table 1).LA indexed volume (LAVi) and LA strain did not vary between MR and MS, but strain rate did. SRs and SRe had better values in MR, whereas SRa had worse values in MR (table 1). SRe ( CONCLUSIONS LA strain rate phases were the only parameters that varied between MR and MS. Contractile phase strain rate was more impaired in MR and conduit phase strain rate in MS. This highly specific data reflect the earlier hemodynamic changes occurring in LA in the setting of mitral valve disease. mMR mMS P value LVEF (±SD,%) 57.4 ± 6.4 59.6 ± 4.6 0.145 LV-GLS (±SD, %) -17.7 ± 4.5 -17.1 ± 3.5 0.587 sPAP (±SD, mmHg) 30.3 ± 10.5 32.4 ± 8.3 0.387 LAVi (± SD, ml/m2) 46.3 ± 6.4 48.2 ± 7.4 0.281 LAɛs (± SD, %) 15.8 ± 7.3 13.3 ± 9 0.062 LAɛe (± SD, %) 8.4 ± 4.7 7.1 ± 5.4 0.074 LAɛa (± SD, %) 6.3 ± 4.8 7.4 ± 4.5 0.081 LA SRs (± SD, %) 0.8 ± 0.4 0.6 ± 0.3 0.004 LA SRe (± SD, %) -0.9 ± 0.5 -0.5 ± 0.3

Background An individualized approach should be taken regarding the utilization of direct oral anticoagulants (DOAC) in frail and elderly populations with atrial fibrillation (AF). We hypothesized that among an elderly and frail population, where the risk of bleeding, both real and perceived, is very high, the proportion of patients with a dose regimen different from the formal indication would be particularly high due to potential underdosing. Methods We conducted a retrospective, observational study enrolling 327 patients with AF admitted to an Internal Medicine ward during a 1-year period and discharged with a DOAC prescription. We divided the population in 2 groups: patients prescribed a reduced dose without formal dose reduction criteria (underdosed, n=170) and the rest of the population (n=157), which included adequately dosed patients, both with normal dose (n=99) and correctly reduced dose (n=43) and overdosed patients (n=15). A 1-year follow-up was completed for all patients, assessing the following outcomes: all-cause mortality, stroke, systemic embolism and major bleeding. Results Patients were elderly (81.9±7.68) and frail (Katz index 3.35±2.36). Apixaban was the most commonly prescribed NOAC (38.8%), followed by rivaroxaban (36.4%) and dabigatran (24.8%). Among underdosed patients, apixaban was prescribed in 45.3% of patients, dabigatran in 29.4% and rivaroxaban 25.3%. Although only 18.3% of patients had clinical criteria for dose reduction, 65.4% were discharged with reduced dose and thus 52% were underdosed. Regarding 1-year outcomes, mortality (40.8% vs 25.5%, RR=1.6, p=0.003) and the combined stroke, systemic embolism and major bleeding event rate (10.1% vs 3.2%, RR=3.16, p=0.015) were higher for underdosed patients. Among underdosed patients, comparing with the rest of the population, the increased ischemic events rate (ischemic stroke and systemic embolism) did not reached statistical significance (3.7% vs. 1.9%, p=0.5), but it did for hemorrhagic events (major bleeding and hemorrhagic stroke) (6.1% vs 0.6%, p=0.01) On multivariate analysis, even after considering adjustment for age, Katz and CHAD2VAS2C scores, renal function and DOAC prescribed, DOAC underdosing was associated with a higher risk of both ischemic and hemorrhagic events (HR = 3.51, 95% CI 1.08–11.38). However, it lost its independent negative effect regarding mortality (HR 1.32, 95% CI 0.87–1.99). Survival and event rate in underdosed Conclusions There is a significant proportion of frail and elderly patients with AF that are underdosed. This subset has a significant survival disadvantage, eventually reflecting prescription bias. However, underdosed patients have also a higher event rate of both ischemic and hemorrhagic events, suggesting that underdosing fragile patients is not an effective strategy and that instead it may be hazardous.

Resume Le syndrome de Papillon-Lefevre (SPL) est une affection autosomique recessive due a des mutations du gene de la cathepsine C responsables d’un deficit immunitaire rare associe a une parodontopathie severe, une edentation et une keratose palmoplantaire (KPP). C’est une alteration des fonctions du polynucleaire (PN) qui entraine une dysbiose gingivale avec pullulation microbienne et inflammation intense du parodonte. Nous rapportons l’observation d’une fillette âgee de 4 ans qui presentait une gingivite avec edentation lacteale partielle associee a une KPP dont le diagnostic, porte avec retard, a ete confirme par le deficit de l’activite cathepsine C et la presence d’une mutation heterozygote bi-allelique dans l’exon 4 c.628C > T, pArg210*, et dans l’exon 7 c.1286G > A, p.Trp429*. La prise en charge stomatologique et dermatologique a transforme le pronostic fonctionnel, esthetique et psychologique de cette enfant. Cette observation permet de rappeler le phenotype clinique et biologique de ce syndrome mal connu.

Papillon-Lefèvre syndrome (PLS) is a rare primary immunodeficiency, which combines severe periodontal disease with edentulism and palmoplantar keratosis (PPK). PLS is inherited as an autosomal recessive trait and is due to mutations in the cathepsin C gene. The biological properties of the neutrophils (PN) are altered, leading to a gingival dysbiosis and bacterial overgrowth, with intense inflammation of the periodontium. We report the observation of a 4-year-old girl who presented to the clinic with gingivitis, partial edentulism, and PPK, whose diagnosis, raised after a long delay, was suggested by null cathepsin C activity and confirmed by the presence of heterozygous mutations in exon 4: c.628CT, pArg210* and in exon 7: c.1286GA, p.Trp429*. A multidisciplinary approach transformed the functional and esthetic prognosis and psychological behavior of this child. This classical observation describes this poorly known phenotype.

Resumo: A síndroma de Mounier-Kuhn é uma doença rara, de etiologia desconhecida e que se presume subdiagnosticada. Cursa frequentemente com infecções respiratórias de repetição e bronquiectasias. A clínica inespecífica, semelhante a outras patologias supurativas brônquicas crónicas, dificulta o diagnóstico, muitas vezes efectuado vários anos após o início dos sintomas. Os autores apresentam uma revisão da literatura a propósito de dois casos clínicos que ilustram a heterogeneidade e as dificuldades diagnósticas desta entidade nosológica. Um dos doentes encontrava-se em idade pediátrica na altura do diagnóstico e outro na quarta década de vida. Abstract: The incidence of the syndrome may be greater than is suspected. Patients present with recurrent respiratory infections and bronchiectasis. The symptoms are non-specific and indistinguishable from those of other chronic respiratory diseases. The diagnosis is often made several years after the first clinical complaints. The authors perform a brief review of the literature and report two cases of Mounier--Kuhn syndrome. One of the patients was diagnosed in childhood and the other in the fourth decade of life. Palavras-chave: Síndroma de Mounier-Kuhn, traqueobroncomegalia, infecções respiratórias de repetição, Key-words: Mounier-Kuhn syndrome, tracheobronchomegaly, recurrent respiratory infections

In a hierarchy of increasing complexity of physical forcing mechanisms, we conduct a process-oriented study of the Northern Canary Current System (NCCS) with a terrain-following numerical ocean model (in this case the Princeton Ocean Model, POM) to investigate the forcing mechanisms for the classical as well as unique features of the NCCS. While most of the NCCS features are realistically simulated, a key comparison of the results shows that unexpectedly a realistic subsurface mesoscale feature is simulated in a flat bottom NCCS model but not in the same model with bottom topography. We then show that this is a consequence of a numerical choice, which leads to the use of an improved technique to smooth the bottom topography, which better preserves the raw topography and subsequently is shown to produce the subsurface feature. This choice is then used in the final and most realistic of the NCCS experiments, in which a high temporal resolution study is conducted from March to September 1996 for the NCCS coastal ocean domain using daily winds and thermohaline forcing initialized on 2 March 1996 from a one-way coupled North Atlantic Parallel Ocean Program (POP) model updated at the lateral boundaries of the POM model every three days. A key physical result is that a dynamic flow consistent with the Azores Current is produced in this experiment, a feature not produced in the other experiments which used climatological data at the open boundaries. The results of these process-oriented experiments emphasize that numerical models of ocean circulation require important choices, which are both numerical and physical.

The article of record as published may be found at http://dx.doi.org/10.1016/j.ocemod.2006.01.003 Sigma coordinate ocean models, such as the Princeton Ocean Model, are a type of terrain-following model, which are currently being used in regions with large topographic variability such as entire ocean basins, shelf breaks, continental shelves, estuaries and bays. The main concern when using a terrain-following ocean model is to reduce the pressure gradient force error (PGFE). Regardless of the method of calculation of the pressure gradient, the PGFE will not be reduced to an acceptable value without first reducing the slope parameter, defined by the absolute value of the ratio of the difference between two adjacent cell depths and their mean depth. Here two methods for reducing the slope parameter are compared: a traditional two-dimensional smoothing with Gaussian filters and an alternative one-dimensional robust direct iterative technique. While both methods efficiently smooth the bottom topography so that the pressure gradient errors are reduced to acceptable levels, the alternative method is shown to have a unique advantage of maintaining coastline irregularities, continental shelves, and relative maxima such as seamounts and islands.

Pollution insurance systems are a tool with a strong potential in environmental management. However, the implementation of such systems can be troublesome mainly due to the lack of a stable and clear liability regime, and to difficulties in identifying activity risks, in estimating damage magnitude and placing monetary value on the resulting ecological damages.

Rett syndrome is a progressive encephalopathy restricted to the female sex. In the present paper a possible genetic cause for this syndrome is discussed, based on data from the literature as well as our own. Our results are in agreement with others regarding no increase in parental age, or in spontaneous abortions rate among the mothers of affected children and with a normal sex ratio among sibs. We have found no chromosome rearrangement detectable with the methods used and no correlation between fra(X) (p22) and the Rett syndrome. We have observed an alteration in the sequence of replication in one of the two types of late-replicating X-chromosome present in normal women, and suggest that this may signify that genes which are active in the late-replicating X-chromosome are inactivated (or vice-versa) in these patients. This fact could be related to the abnormal phenotype observed in Rett syndrome patients.