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PurposeIn this study, we describe the phenotype and genotype of the largest cohort of patients with Joubert syndrome (JS) carrying pathogenic variants on one of the most frequent causative genes,CC2D2A.MethodsWe selected 53 patients with pathogenic variants onCC2D2A, compiled and analysed their clinical, neuroimaging and genetic information and compared it to previous literature.ResultsDevelopmental delay (motor and language) was nearly constant but patients had normal intellectual efficiency in 74% of cases (20/27 patients) and 68% followed mainstream schooling despite learning difficulties. Epilepsy was found in only 13% of cases. Only three patients had kidney cysts, only three had genuine retinal dystrophy and no subject had liver fibrosis or polydactyly. Brain MRIs showed typical signs of JS with rare additional features. Genotype–phenotype correlation findings demonstrate a homozygous truncating variant p.Arg950* linked to a more severe phenotype.ConclusionThis study contradicts previous literature stating an association betweenCC2D2A-related JS and ventriculomegaly. Our study implies thatCC2D2A-related JS is linked to positive neurodevelopmental outcome and low rate of other organ defects except for homozygous pathogenic variant p.Arg950*. This information will help modulate patient follow-up and provide families with accurate genetic counselling.

To use Quality Indicators to study the management of ST segment elevation myocardial infarction (STEMI) in different regions.Prospective cohort study of STEMI within 24 hours of symptom onset (11,462 patients, 196 centres, 26 ESC member and 3 affiliated countries). The median delay between arrival at a PCI centre and primary PCI was 40 min (IQR 20 to 74) with 65.8% receiving PCI within guideline recommendation of 60 min. A third of patients (33.2%) required transfer from their initial hospital to one that could perform emergency PCI for whom only 27.2% were treated within the quality indicator recommendation of 120 mins. Radial access was used in 56.6% of all primary PCI, but with large geographic variation, from 76.4% to 9.1%. Statins were prescribed at discharge to 98.7% of patients, with little geographic variation. Of patients with a history of heart failure or a documented LVEF ≤40%, 84.0% were discharged on an ACEI/ARB and 88.7% were discharged on beta blockers.Care for STEMI shows wide geographic variation in the receipt of timely primary PCI, and is in contrast with the more uniform delivery of guideline-recommended pharmacotherapies at time of hospital discharge.

In this study, we describe the phenotype and genotype of the largest cohort of patients with Joubert syndrome (JS) carrying pathogenic variants on one of the most frequent causative genes,We selected 53 patients with pathogenic variants onDevelopmental delay (motor and language) was nearly constant but patients had normal intellectual efficiency in 74% of cases (20/27 patients) and 68% followed mainstream schooling despite learning difficulties. Epilepsy was found in only 13% of cases. Only three patients had kidney cysts, only three had genuine retinal dystrophy and no subject had liver fibrosis or polydactyly. Brain MRIs showed typical signs of JS with rare additional features. Genotype-phenotype correlation findings demonstrate a homozygous truncating variant p.Arg950* linked to a more severe phenotype.This study contradicts previous literature stating an association between

Resumen Introduccion y objetivos La insuficiencia cardiaca (IC) es un problema creciente de salud y una carga importante para la sociedad. Pese a ello, con frecuencia se minusvalora globalmente la gravedad del pronostico. Este estudio estima el pronostico al ano en pacientes con IC aguda y cronica en Espana y resto de Europa. Metodos Un total de 2.829 pacientes con IC (589 IC aguda y 2.240 IC cronica) seleccionados en 27 centros hospitalarios en Espana, atendidos por cardiologos y que participan en el registro ESC-EORP-HFA Heart Failure Long-Term, con 211 centros y 12.440 pacientes en total, se siguieron un ano para monitorizar la mortalidad y el ingreso hospitalario. Resultados La mortalidad al ano en IC aguda fue del 29,3% en Espana (IC95%, 25,6-33,2) y 27,7% en el resto de Europa (p = 0,4303). En IC cronica, las cifras correspondientes fueron 6,4% (IC95%, 5,4-7,5) y 9,5% (p Conclusiones Se confirma la gravedad de la IC, en particular cuando ya necesita ingreso, incluso en centros con buen seguimiento de guias clinicas. En pacientes ingresados por IC en Espana casi un tercio fallecera en el primer ano tras ese ingreso indice (incluyendo el 5,9% que fallece durante el mismo) y casi la mitad fallecera o necesitara reingresar por IC. La comparacion favorable con Europa en hospitalizaciones y mortalidad en IC cronica se debe interpretar con cautela por insuficiente ajuste por potenciales variables de confusion.

Background Adenosine can be used to reveal dormant pulmonary vein (PV) conduction after PV isolation (PVI). This study presents a subanalysis of real-world 1-year follow-up data from the ESC-EHRA EORP Atrial Fibrillation (AF) Ablation Long-Term registry to analyze the usage of adenosine during PVI treatment in terms of rhythm outcome and safety. Methods The registry consists of 104 participating centers in 27 countries within the European Society of Cardiology. The registry data was split into an adenosine group (AG) and no-adenosine group (NAG). Procedure characteristics and patient outcome were compared. Results Adenosine was administered in 10.8% of the 3591 PVI patients included in the registry. Spain, the Netherlands, and Italy included the majority of adenosine cases (48.8%). Adenosine was applied more often in combination with open irrigation radiofrequency (RF) energy (74.7%) and less often in combination with nonirrigated RF energy (1.6%). After 1 year, a higher percentage of the AG was free from AF compared with the NAG (68.9% vs 59.1%, p p p = 0.991). Conclusions The use of adenosine was associated with a better rhythm outcome after 1 year follow-up and seems more useful in patients treated with RF energy compared with patients treated with cryo energy. Given the improved rhythm outcome at 1-year follow-up, it seems reasonable to encourage the use of adenosine during RF AF ablation.

Aims Rhythm control management in patients with atrial fibrillation (AF) may be unequal across Europe. The aim of this study was to investigate how selective the patient cohort referred for AF ablation is, as compared to the general AF population in Europe, and to describe the governing mechanisms for such selection. Methods and results Descriptive comparative statistical analyses of the baseline characteristics were performed between the cohorts of Atrial Fibrillation Ablation Long-Term (ESC EORP AFA-LT) registry, designed to provide a picture of contemporary real-world AF ablation, and the AF population from the AF-General (ESC EORP AF-Gen) pilot registry. Data collection was performed using a web-based system. In the AFA and in the Atrial Fibrillation General (AFG) pilot registries, 3593 and 3049 patients were enrolled, respectively. Patients who underwent AF ablation were younger, more commonly male, and had significantly less comorbidities. Atrial Fibrillation Ablation patients often presented without comorbidities, resulting in a lower risk of stroke (CHA2DS2-VASc ≥5: 2.9% vs. 24.5%, all P 1 and more prevalent AF-related symptoms such as palpitations, fatigue, and weakness (all P Conclusion The comparison of the patient cohorts in the AFA and AFG registries showed that AF ablation in European clinical practice is mostly performed in relatively young, symptomatic and relatively healthy patients.

Background Multiple acyl-CoA dehydrogenase deficiency (MADD), previously called glutaric aciduria type II, is a rare congenital metabolic disorder of fatty acids and amino acids oxidation, with recessive autosomal transmission. The prevalence in the general population is estimated to be 9/1,000,000 and the prevalence at birth approximately 1/200,000. The clinical features of this disease are divided into three groups of symptoms linked to a defect in electron transfer flavoprotein (ETF) metabolism. In this case report, we present new pathogenic variations in one of the two ETF protein subunits, called electron transfer flavoprotein alpha (ETFA), in a childhood-stage patient with no antecedent. Case presentation A five-year-old child was admitted to the paediatric emergency unit for seizures without fever. He was unconscious due to hypoglycaemia confirmed by laboratory analyses. At birth, he was a eutrophic full-term new-born with a normal APGAR index (score for appearance, pulse, grimace, activity, and respiration). He had one older brother and no parental consanguinity was reported. A slight speech acquisition delay was observed a few months before his admission, but he had no schooling problems. MADD was suspected based on urinary organic acids and plasma acylcarnitine analyses and later confirmed by genetic analysis, which showed previously unreported ETFA gene variations, both heterozygous (c.354C > A (p.Asn118Lys) and c.652G > A (p.Val218Met) variations). Treatment was based on avoiding fasting and a slow carbohydrate-rich evening meal associated with L-carnitine supplementation (approximately 100 mg/kg/day) for several weeks. This treatment was maintained and associated with riboflavin supplementation (approximately 150 mg/day). During follow up, the patient exhibited normal development and normal scholastic performance, with no decompensation. Conclusion This case report describes new pathogenic variations of the ETFA gene. These compound heterozygous mutations induce the production of altered proteins, leading to a mild form of MADD.

Background: Infections of cardiac implantable devices (CIEDI) have poor outcomes despite improvement in lead extraction (TLE) procedures. Methods: To explore the influence of CIEDI on the outcomes of TLE and the differences between patients with systemic (Sy) vs. local (Lo) CIEDI, we performed a sub-analysis of the EORP ELECTRa (European Lead Extraction ConTRolled) Registry. Results: Among 3555 patients enrolled by 73 centers in 19 Countries, the indication for TLE was CIEDI in 1850: 1170 with Lo-CIEDI and 680 with Sy-CIEDI. Patients with CIEDI had a worse in-hospital prognosis in terms of major complications (3.57% vs. 1.71%; p = 0.0007) and mortality (2.27% vs. 0.49%; p < 0.0001). Sy-CIEDI was an independent predictor of in-hospital death (H.R. 2.14; 95%CI 1.06–4.33. p = 0.0345). Patients with Sy-CIEDI more frequently had an initial CIED implant and a higher prevalence of comorbidities, while subjects with Lo-CIEDI had a higher prevalence of previous CIED procedures. Time from signs of CIEDI and TLE was longer for Lo-CIEDI despite a shorter pre-TLE antibiotic treatment. Conclusions: Patients with CIEDI have a worse in-hospital prognosis after TLE, especially for patients with Sy-CIEDI. These results raise the suspicion that in a relevant group of patients CIEDI can be systemic from the beginning without progression from Lo-CIEDI. Future research is needed to characterize this subgroup of patients.

AimsPurpose of this study is to compare the clinical course and outcome of patients with recurrent versus first-episode infective endocarditis (IE).MethodsPatients with recurrent and first-episode IE enrolled in the EUROpean ENDOcarditis (EURO-ENDO) registry including 156 centres were identified and compared using propensity score matching. Recurrent IE was classified as relapse when IE occurred ≤6 months after a previous episode or reinfection when IE occurred >6 months after the prior episode.Results3106 patients were enrolled: 2839 (91.4%) patients with first-episode IE (mean age 59.4 (±18.1); 68.3% male) and 267 (8.6%) patients with recurrent IE (mean age 58.1 (±17.7); 74.9% male). Among patients with recurrent IE, 13.2% were intravenous drug users (IVDUs), 66.4% had a repaired or replaced valve with the tricuspid valve being more frequently involved compared with patients with first-episode IE (20.3% vs 14.1%; p=0.012). In patients with a first episode of IE, the aortic valve was more frequently involved (45.6% vs 39.5%; p=0.061). Recurrent relapse and reinfection were 20.6% and 79.4%, respectively.Staphylococcus aureuswas the microorganism most frequently observed in both groups (p=0.207). There were no differences in in-hospital and post-hospitalisation mortality between recurrent and first-episode IE. In patients with recurrent IE, in-hospital mortality was higher in IVDU patients. Independent predictors of poorer in-hospital and 1-year outcome, including the occurrence of cardiogenic and septic shock, valvular disease severity and failure to undertake surgery when indicated, were similar for recurrent and first-episode IE.ConclusionsIn-hospital and 1-year mortality was similar in patients with recurrent and first-episode IE who shared similar predictors of poor outcome.

BACKGROUND There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS). OBJECTIVES This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey. METHODS Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention. RESULTS A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001). CONCLUSIONS A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians. (J Am Coll Cardiol 2021;78:2131-2143) (c) 2021 by the American College of Cardiology Foundation.

Mutations in the ganglioside-induced differentiation associated protein 1 (GDAP1) gene have been associated with demyelinating and axonal forms of Charcot-Marie-Tooth (CMT) disease, the most frequent hereditary peripheral neuropathy in humans. Previous studies reported the prevalent GDAP1 expression in neural tissues and cells, from animal models. Here, we described the first GDAP1 functional study on human induced-pluripotent stem cells (hiPSCs)-derived motor neurons, obtained from normal subjects and from a CMT2H patient, carrying the GDAP1 homozygous c.581C&gt, G (p.Ser194*) mutation. At mRNA level, we observed that, in normal subjects, GDAP1 is mainly expressed in motor neurons, while it is drastically reduced in the patient’s cells containing a premature termination codon (PTC), probably degraded by the nonsense-mediated mRNA decay (NMD) system. Morphological and functional investigations revealed in the CMT patient’s motor neurons a decrease of cell viability associated to lipid dysfunction and oxidative stress development. Mitochondrion is a key organelle in oxidative stress generation, but it is also mainly involved in energetic metabolism. Thus, in the CMT patient’s motor neurons, mitochondrial cristae defects were observed, even if no deficit in ATP production emerged. This cellular model of hiPSCs-derived motor neurons underlines the role of mitochondrion and oxidative stress in CMT disease and paves the way for new treatment evaluation.

Background: The current practice of atrial fibrillation ablation (AFA) as a treatment option for atrial fibrillation (AF) in patients with heart failure (HF) across Europe, their clinical profiles and outcomes is still undefined. Methods: The European Society of Cardiology (ESC) led a prospective observational registry of consecutive patients undergoing AFA, in 27 member countries. The subgroup of patients with HF, followed-up for 1 year, was analyzed and the results are reported. Results: Of the 3582 AF patients in the Registry, 537 (14.9%) had HF. Diabetes, hypertension, hypercholesterolemia, CHA 2DS 2-VASc score ≥ 2, structural heart disease and persistent AF were more common in HF than non-HF patients (all p < 0.001). However the in-hospital complications were less frequent in HF patients (5.0% vs. 8.2% p = 0.01). Both in-hospital and 1-year outcomes, including 1-year AF recurrence (15.4%) and repeat ablations (9.5%), were similar in both groups. We subdivided HF patients according to their left ventricular ejection fraction (EF) at baseline into reduced (HFrEF

Aims Hypertensive disorders occur in women with peripartum cardiomyopathy (PPCM). How often hypertensive disorders co-exist, and to what extent they impact outcomes, is less clear. We describe differences in phenotype and outcomes in women with PPCM with and without hypertensive disorders during pregnancy. Methods and results The European Society of Cardiology EURObservational Research Programme PPCM Registry enrolled women with PPCM from 2012-2018. Three groups were examined: (i) women without hypertension (PPCM-noHTN); (ii) women with hypertension but without pre-eclampsia (PPCM-HTN); (iii) women with pre-eclampsia (PPCM-PE). Maternal (6-month) and neonatal outcomes were compared. Of 735 women included, 452 (61.5%) had PPCM-noHTN, 99 (13.5%) had PPCM-HTN and 184 (25.0%) had PPCM-PE. Compared to women with PPCM-noHTN, women with PPCM-PE had more severe symptoms (New York Heart Association class IV in 44.4% vs. 29.9%, P < 0.001), more frequent signs of heart failure (pulmonary rales in 70.7% vs. 55.4%, P = 0.002), a higher baseline left ventricular ejection fraction (LVEF) (32.7% vs. 30.7%, P = 0.005) and a smaller left ventricular end-diastolic diameter (57.4 +/- 6.7 mm vs. 59.8 +/- 8.1 mm, P = 0.001). There were no differences in the frequencies of death from any cause, rehospitalization for any cause, stroke, or thromboembolic events. Compared to women with PPCM-noHTN, women with PPCM-PE had a greater likelihood of left ventricular recovery (LVEF >= 50%) (adjusted odds ratio 2.08, 95% confidence interval 1.21-3.57) and an adverse neonatal outcome (composite of termination, miscarriage, low birth weight or neonatal death) (adjusted odds ratio 2.84, 95% confidence interval 1.66-4.87). Conclusion Differences exist in phenotype, recovery of cardiac function and neonatal outcomes according to hypertensive status in women with PPCM.

Aims Monitoring of patients after ablation had wide variations in the ESC-EHRA atrial fibrillation ablation long-term (AFA-LT) registry. We aimed to compare four different monitoring strategies after catheter AF ablation. Methods and results The ESC-EHRA AFA-LT registry included 3593 patients who underwent ablation. Arrhythmia monitoring during follow-up was performed by 12-lead electrocardiogram (ECG), Holter ECG, trans-telephonic ECG monitoring (TTMON), or an implanted cardiac monitoring (ICM) system. Patients were selected to a given monitoring group according to the most extensive ECG tool used in each of them. Comparison of the probability of freedom from recurrences was performed by censored log-rank test and presented by Kaplan–Meier curves. The rhythm monitoring methods were used among 2658 patients: ECG (N = 578), Holter ECG (N = 1874), TTMON (N = 101), and ICM (N = 105). A total of 767 of 2658 patients (28.9%) had AF recurrences during follow-up. Censored log-rank test discovered a lower probability of freedom from relapses, which was detected with ICM compared to TTMON, ECG, and Holter ECG (P Conclusion Comparing all main electrocardiographic monitoring methods in a large patient sample, our results suggest that post-ablation recurrences of AF are significantly underreported by TTMON, ECG, and Holter ECG. The ICM estimates AF ablation recurrences most reliably and should be a preferred mode of monitoring for trials evaluating novel AF ablation techniques.

Clinical characteristics of heart failure patients undergoing atrial fibrillation ablation today in Europe. Data from the atrial fibrillation registries of the European Society of Cardiology and the European Heart Rhythm Association.

International audience; Objective - We aimed to characterize epilepsy of infancy with migrating focal seizures (EIMFS), a rare, severe early onset developmental epilepsy related to KCNT1 mutation, and to define specific electroencephalography (EEG) markers using EEG quantitative analysis. The ultimate goal would be to improve early diagnosis and to better understand seizure onset and propagation of EIMFS as compared to other early onset developmental epilepsy. Methods - EEG of 7 EIMFS patients with KCNT1 mutations (115 seizures) and 17 patients with other early onset epilepsies (30 seizures) was included in this study. After detection of seizure onset and termination, spatiotemporal characteristics were quantified. Seizure propagation dynamics were analyzed using chronograms and phase coherence. Results - In patients with EIMFS, seizures started and were localized predominantly in temporal and occipital areas, and evolved with a stable frequency (4-10 Hz). Inter- and intrahemispheric migrations were present in 60% of EIMFS seizures with high intraindividual reproducibility of temporospatial dynamics. Interhemispheric migrating seizures spread in 71% from temporal or occipital channels to the homologous contralateral ones, whereas intrahemispheric seizures involved mainly frontotemporal, temporal, and occipital channels. Causality links were present between ictal activities detected under different channels during migrating seizures. Finally, time delay index (based on delays between the different ictal onsets) and phase correlation index (based on coherence of ictal activities) allowed discrimination of EIMFS and non-EIMFS seizures with a specificity of 91.2% and a sensitivity of 84.4%. Significance - We showed that the migrating pattern in EIMFS is not a random process, as suggested previously, and that it is a particular propagation pattern that follows the classical propagation pathways. It is notable that this study reveals specific EEG markers (time delay and phase correlation) accessible to visual evaluation, which will improve EIMFS diagnosis.

Funding Acknowledgements Type of funding sources: None. Introduction The ESC-EHRA EORP AF General Long-Term Registry provides a contemporary snapshot of European atrial fibrillation (AF) patients’ characteristics and management. Aims: We present data about the final 2-years follow-up observation of AF patients enrolled in the ESC-EHRA EORP AF General Long-Term Registry. Methods A contemporary evaluation of residual risk of adverse outcomes in a cohort of largely anticoagulated AF patients according to the baseline thromboembolic and bleeding risk, defined according to CHA2DS2-VASc and HAS-BLED scores. We determined cardiovascular (CV) events, CV death and all-cause death as outcomes. Results Among the original 11069 patients enrolled, 8409 (76.0%) patients had available follow-up status at the end of the 2-years follow-up. Patients age, female sex and most comorbidities were progressively more prevalent across the spectrum of thromboembolic and bleeding risk. Data on adverse outcomes were available for 10087 (91.1%), over the 2-year observation period. Outcome rates were progressively higher across CHA2DS2-VASc and HAS-BLED scores (all p Conclusions In this large contemporary European-wide cohort of AF patients, both baseline thromboembolic and bleeding risks were associated to an increased risk of major clinical outcomes. Both scores are reflective of high risk clinical states, and are predictive of major adverse outcomes even in a large cohort of largely anticoagulated patients with a lower residual risk of adverse outcomes. Abstract Figure.

Aims To determine the current state of the use of reperfusion and adjunctive therapies and in-hospital outcomes in European Society of Cardiology (ESC) member and affiliated countries for patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS). Methods and results ESC EurObservational Research Programme prospective international cohort study of admissions with STEMI within 24 h of symptom onset (196 centres; 26 ESC member and 3 affiliated countries). Of 11 462 patients enrolled, 448 (3.9%) had CS. Patients with compared to patients without CS, less frequently received primary percutaneous coronary intervention (PCI) (65.5% vs. 72.2%) and fibrinolysis (15.9% vs. 19.0), and more often had no reperfusion therapy (19.0% vs. 8.5%). Mechanical support devices (intraaortic ballon pump 11.2%, extracoporeal membrane oxygenation 0.7%, other 1.1%) were used infrequently in CS. Bleeding definition academic research consortium 2–5 bleeding complications (10.1% vs. 3.0%, P Conclusion In this multi-national registry, patients with STEMI complicated by CS less frequently receive reperfusion therapy than patients with STEMI without CS. Early mortality in patients with CS not treated with primary PCI is very high. Therefore, strategies to improve clinical outcome in STEMI with CS are needed.

Aims: \ud In peripartum cardiomyopathy (PPCM), electrocardiography (ECG) and its relationship to echocardiography have not yet been investigated in large multi-centre and multi-ethnic studies. We aimed to identify ECG abnormalities associated with PPCM, including regional and ethnic differences, and their correlation with echocardiographic features.\ud \ud Methods and results: \ud We studied 411 patients from the EURObservational PPCM registry. Baseline demographic, clinical, and echocardiographic data were collected. ECGs were analysed for rate, rhythm, QRS width and morphology, and QTc interval. The median age was 31 [interquartile range (IQR) 26–35] years. The ECG was abnormal in > 95% of PPCM patients. Sinus tachycardia (heart rate > 100 b.p.m.) was common (51%), but atrial fibrillation was rare (2.27%). Median QRS width was 82 ms [IQR 80–97]. Left bundle branch block (LBBB) was reported in 9.30%. Left ventricular (LV) hypertrophy (LVH), as per ECG criteria, was more prevalent amongst Africans (59.62%) and Asians (23.17%) than Caucasians (7.63%, P < 0.001) but did not correlate with LVH on echocardiography. Median LV end-diastolic diameter (LVEDD) was 60 mm [IQR 55–65] and LV ejection fraction (LVEF) 32.5% [IQR 25–39], with no significant regional or ethnic differences. Sinus tachycardia was associated with an LVEF < 35% (OR 1.85 [95% CI 1.20–2.85], P = 0.006). ECG features that predicted an LVEDD > 55 mm included a QRS complex > 120 ms (OR 11.32 [95% CI 1.52–84.84], P = 0.018), LBBB (OR 4.35 [95% CI 1.30–14.53], P = 0.017), and LVH (OR 2.03 [95% CI 1.13–3.64], P = 0.017).\ud \ud Conclusions: \ud PPCM patients often have ECG abnormalities. Sinus tachycardia predicted poor systolic function, whereas wide QRS, LBBB, and LVH were associated with LV dilatation.

Background: Retrospective analyses of clinical trials indicate that elevated serum uric acid (sUA) predicts poor outcome in heart failure (HF). Uric acid can contribute to inflammation and microvascular dysfunction, which may differently affect different left ventricular ejection fraction (LVEF) phenotypes. However, role of sUA across LVEF phenotypes is unknown. Objectives: We investigated sUA association with outcome in a prospective cohort of HF patients stratified according to LVEF. Methods: Through the Heart Failure Long-Term Registry of the European Society of Cardiology (ESC-EORP-HFLT), 4,438 outpatients were identified and classified into: reduced (= 50% HFpEF) LVEF. Endpoints were the composite of cardiovascular death/HF hospitalization, and individual components. Results: Median sUA was 6.72 (IQ:5.48-8.20) mg/dl in HFrEF, 6.41 (5.02-7.77) in HFmrEF, and 6.30 (5.20-7.70) in HFpEF. At a median 372-day follow-up, the composite endpoint occurred in 648 (13.1%) patients, with 176 (3.6%) deaths and 538 (10.9%) HF hospitalizations. Compared with lowest sUA quartile (Q), Q-III and Q-IV were significantly associated with the composite endpoint (adjusted HR 1.68: 95% CI 1.11-2.54; 2.46: 95% CI 1.66-3.64, respectively). By univariable analyses, HFrEF and HFmrEF patients in Q-III and Q-IV, and HFpEF patients in Q-IV, showed increased risk for the composite endpoint (P

International audience; Objective: To perform genotype-phenotype, clinical and molecular analysis in a large 3-generation family with autosomal dominant congenital spinal muscular atrophy.Methods: Using a combined genetic approach including whole genome scanning, next generation sequencing-based multigene panel, whole genome sequencing, and targeted variant Sanger sequencing, we studied the proband and multiple affected individuals of this family who presented bilateral proximal lower limb muscle weakness and atrophy.Results: We identified a novel heterozygous variant, c.1826T > C; p.Ile609Thr, in the DYNC1H1 gene localized within the common haplotype in the 14q32.3 chromosomal region which cosegregated with disease in this large family. Within the family, affected individuals were found to have a wide array of clinical variability. Although some individuals presented the typical lower motor neuron phenotype with areflexia and denervation, others presented with muscle weakness and atrophy, hyperreflexia, and absence of denervation suggesting a predominant upper motor neuron disease. In addition, some affected individuals presented with an intermediate phenotype characterized by hyperreflexia and denervation, expressing a combination of lower and upper motor neuron defects.Conclusion: Our study demonstrates the wide clinical variability associated with a single disease causing variant in DYNC1H1 gene and this variant demonstrated a high penetrance within this large family.

Background Previous studies on paediatric cardiomyopathies have provided useful information on their epidemiology and clinical presentation but have been limited by a lack of detailed data on genetic testing and aetiology. Purpose The purpose of this study was to examine the frequency of familial and genetic disease among children with cardiomyopathy enrolled in the European Society of Cardiology (ESC) Cardiomyopathy and Myocarditis EORP Long-Term Registry (CMY-LT). Methods 633 individuals aged Results Overall, 253 patients (47% of those reported) had familial disease; in those diagnosed between 10 and 18 years of age, familial disease was most frequent in HCM and least frequent in DCM [57 (55%) vs 12 (32%); p=0.046]. Genetic testing was performed in 414 (68%) patients. In those diagnosed Conclusion This study confirms the heterogeneous aetiology of childhood cardiomyopathies and demonstrate a higher prevalence of familial disease than previously reported in paediatric populations. Genetic testing is performed in a high proportion of patients, with a high yield of reported causative variants. Funding Acknowledgement Type of funding source: None

Introduction The impact of body mass index (BMI) on outcomes in patients with atrial fibrillation (AF) has been largely debated. Aims To describe the relationship between BMI categories and clinical outcomes in a large cohort of European AF patients. Methods We included all AF patients with available baseline BMI and creatinine clearance and 1-year follow-up data enrolled in the EORP-AF General Long-Term Registry. Outcomes considered were: i) a composite of any thromboembolic event (TE)/acute coronary syndrome (ACS)/cardiovascular (CV) death; ii) CV death; iii) all-cause death. Results A total of 7,759 patients were included in this analysis. Of these, 55 (0.7%) were underweight, 2,074 (26.7%) were normal weight, 3,170 (40.9%) were overweight, 1,703 (21.9%) were obese and 757 (9.8%) were severe obese. Mean age was progressively lower across the categories (p Conclusions In a large cohort of European AF patients a progressively lower rate of outcomes was found across increasing BMI classes. After full adjustments, no significant association was found between the higher BMI classes and outcomes. Underweight was associated with an increased risk for CV death and all-cause death. Figure 1. Outcomes at 1-year Follow-up Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Since the start of EORP programme, several companies have supported it with unrestricted grants

Background The Myocarditis section of the EORP Cardiomyopathy and Myocarditis Long-term Registry is a prospective, observational, multinational registry of adult and pediatric patients enrolled using the ESC 2013 diagnostic criteria of clinically suspected (CS) or biopsy-proven (BP) myocarditis (myoc). Purpose i) To obtain a real-world snapshot of features and management of myoc; ii) to assess features at presentation in CS and in BP myoc and by age. Methods 581 patients (68% male), 493 adults, aged 34.9 (SD 18.5) years, and 88 children, aged 8.1 (SD 5.2) years, were divided into 3 groups (G): G1 (n=234, 40%), CS myoc plus cardiac magnetic resonance (CMR) confirmed; G2 (n=222, 38,2%), BP myoc; G3 (n=125, 21.5%), CS myoc, no or normal or inconclusive CMR. Baseline features, procedures, medications were analysed in the total population, in adults vs children, and among G. Results In all patients: pseudo-infarct presentation with normal coronary arteries is common (58%), as is heart failure (HF) with or without chest pain and troponin release (58%), followed by arrhythmia (41.9%). In children new-onset HF is more common than in adults (29/32, 90% vs 90/190, 47%, p=0.001). In both adult and pediatric G2 BP myoc, HF and arrhythmia were more common than in CS myoc. Left and right ventricular (RV) echocardiography and CMR function indexes and troponins were lower, NT-pro BNP was higher in G2 BP myoc vs G1 and G3 CS myoc. On CMR oedema and/or Late Gadolinium Enhancement (LGE) were found in 57.4% of adult and in 31.3% of paediatric G2 BP myoc. Endomyocardial biopsy (EMB) was obtained in a similar proportion in children (31/88, 35.2%) and adults (185/493, 37.5%, p=NS), ventricular assist devices were more commonly implanted in G2 children (8/32, 25%) than in G2 adults (4/190, 2.1%, p=0.001), ICD tended to be less common in G2 children (2/32, 6.3%) than in G2 adults (48/190, 25%, p=0.07). In all patients EMB, mainly RV (75.8%), had a low complication rate (4.7%), similar in adults vs children, with no procedure-related death. Histology findings were: lymphocitic myoc (78.9%), giant cell (10.9%), sarcoid (6.9%), non specific (16%). Viral genome was found in 44% of patients (most common PVB19, 21.7%, HHV6, 9.5%). In all patients HF and antiarrhytmic drugs were more frequently used in G2, antivirals in a patient minority, steroids in 24.7%, immunosuppression (IS) in 22.6%. In children steroids or IS were given regardless of G, in adults mainly to G2 BP myoc patients, in keeping with the ESC 2013 expert reco's. Conclusions EMB is safe in children and adults and is still the diagnostic gold standard, since CMR failed to identify myoc in a high proportion of G2 BP patients. Etiology-directed therapy was used in a minority of G2 cases, and/or regardless of etiology, thus there is room for improved management. G2 BP patients were older, sicker, had worse biventricular function, more medications and ICDs; follow-up may show their worse outcome. Funding Acknowledgement Type of funding source: None

Introduction Increasing age is a well-known determinant for incident atrial fibrillation (AF) as well as for adverse outcomes. With a progressively ageing population in Europe (and elsewhere), contemporary data are needed to investigate the impact of age in relation to major adverse events in AF patients. Purpose To evaluate the impact of increasing age on major adverse outcomes in a contemporary European AF cohort. Methods Patients enrolled in the EORP-AF Long Term General Registry were categorized by age: Results Among the 9762 patients included in this analysis, 2946 (30.2%) were Conclusions In a large contemporary cohort of European AF patients, increasing age was a major determinant of major adverse outcomes. Figure 1. Kaplan-Meier Curves for All-Cause Death Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Since the start of EORP programme, several companies supported its activities with unrestricted grants.

Introduction Cardiomyopathies comprise a heterogeneous group of diseases, often of genetic origin. Purpose We assessed the current practice of genetic counselling and testing of adult cardiomyopathy patients in the prospective ESC EORP cardiomyopathy registry. Methods 3 208 adult patients from sixty-nine centres in 18 countries were enrolled. Clinical data on genetic counselling and testing and on the presentation of cardiomyopathies were gathered. Results Genetic counselling was performed in 60.8% of all patients (75.4% in hypertrophic (HCM), 39.2% in dilated (DCM), 70.8% in arrhythmogenic right ventricular (ARVC) and 49.2% in restrictive cardiomyopathy (RCM), p Conclusion We report on the practice of genetic counselling and testing in cardiomyopathies in Europe. Genetic counselling and testing were performed in a substantial proportion of patients but less often than recommended by European guidelines, and much less in DCM than in HCM and ARVC, despite evidence for genetic background. Funding Acknowledgement Type of funding source: None

Background Cardiac magnetic resonance (CMR) constitutes a gold standard in the diagnosis of cardiomyopathies. Regardless of CMR advantages, the method is time-consuming, high-cost, with limited availability in some European regions. Purpose To assess the availability and applicability of CMR for establishing the diagnosis in different populations of patients with cardiomyopathies. Methods Overall, 3208 adult patients with cardiomyopathy (1119 / 34.9% females; median age at diagnosis: 49.0 years): 1260 with dilated (DCM), 1739 with hypertrophic (HCM), 66 with restrictive (RCM) and 143 with arrhythmogenic right ventricular cardiomyopathy (ARVC) enrolled in EURObservational Research Programme (EORP) – Cardiomyopathy/Myocarditis Long-Term Registry were analysed. Results CMR scan was performed as a baseline diagnostic method in 29.4% of patients; CMR was a single diagnostic method in 0.9% of patients and in 28.6% of patients CMR was used along with transthoracic echocardiography (TTE). In 67.6% of patients TTE was at the baseline the single diagnostic imaging method. Prevalence of CMR use in different cardiomyopathies was as follows: 20.6% in DCM, 33.8% in HCM, 36.4% in RCM and 51.1% in ARVC (p The population with CMR use was younger, less symptomatic, with decreased prevalence of other cardiovascular risk factors and of associated cardiovascular diseases as compared to the population diagnosed without CMR scanning (p Abnormal CMR results were present in 93.4% of patients with the highest percentage in RCM (95.8%) and HCM (94.9%) followed by DCM (91.5%) and the lowest abnormal CMR scan ratio in ARVC (87.7%) (p=0.030). The majority of CMR examinations comprised the assessment of late gadolinium enhancement (LGE, 93.3% at baseline). Presence of CMR LGE was observed in 69.3% of all patients: 59.1% in DCM, 73.8% in HCM, in 63.9% in ARVC and with the highest prevalence in RCM (83.3%) (p Conclusion The study reveals real-life data on the low availability and applicability of CMR in adult patients with cardiomyopathies. The analysis shows the advantages of CMR imaging but also identifies the gaps between recommendations and clinical practice. Improvement regarding access, training and reimbursement is necessary to offer CMR to cardiomyopathy patients in accordance with the ESC guidelines. Funding Acknowledgement Type of funding source: None

Aims The European Society of Cardiology (ESC) European Observational Research Programme (EORP) Cardiomyopathy Registry is a prospective multinational registry of consecutive patients with cardiomyopathies. The objective of this report is to describe the short-term outcomes of adult patients (≥18 years old). Methods and results Out of 3208 patients recruited, follow-up data at 1 year were obtained in 2713 patients (84.6%) [1420 with hypertrophic (HCM); 1105 dilated (DCM); 128 arrhythmogenic right ventricular (ARVC); and 60 restrictive (RCM) cardiomyopathies]. Improvement of symptoms (dyspnoea, chest pain, and palpitations) was globally observed over time (P Conclusions Despite symptomatic improvement, patients with cardiomyopathies remain prone to major clinical events in the short term. Outcomes were different not only according to cardiomyopathy subtypes but also in relatives vs. index patients, and according to European regions.

Aims The COVID-19 pandemic required a significant redeployment of worldwide healthcare resources. Fear of infection, national lockdowns and altered healthcare priorities have the potential to impact utilisation of healthcare resources for non-communicable diseases. To survey health professionals’ views of the impact of the COVID-19 pandemic on the rate and timing of admission of patients with ST-elevation myocardial infarction (STEMI), the European Society of Cardiology (ESC) administered an internet-based questionnaire to cardiologists and cardiovascular nurses across 6 continents. Methods and results 3101 responses were received from 141 countries across 6 continents. 88.3% responded that their country was in “total lockdown” and 7.1% in partial lockdown. 78.8% responded that the number of patients presenting with STEMI was reduced since the coronavirus outbreak and 65.2% indicated that the reduction in STEMI presentations was >40%. Approximately 60% of all respondents reported that STEMI patients presented later than usual and 58.5% that >40% of STEMI patients admitted to hospital presented beyond the optimal window for primary percutaneous intervention (PCI) or thrombolysis. Independent predictors of the reported higher rate of delayed STEMI presentation were a country in total lockdown, >100 COVID-19 cases admitted locally, and the complete restructuring of the local cardiology service. Conclusion The survey indicates that the impact of COVID-19 on STEMI presentations is likely to be substantial, with both lower presentations and a higher rate of delayed presentations occurring. This has potentially important ramifications for future healthcare and policy planning in the event of further waves of this pandemic.

Aims The aim of the study was to investigate differences in clinical outcomes and complication rates among European atrial fibrillation (AF) ablation centres related to the volume of AF ablations performed. Methods and results Data for this analysis were extracted from the ESC EHRA EORP European AF Ablation Long-Term Study Registry. Based on 33rd and 67th percentiles of number of AF ablations performed, the participating centres were classified into high volume (HV) (≥ 180 procedures/year), medium volume (MV) ( Conclusion Low-volume centres tended to present slightly higher cardiovascular complications’ and stroke incidence and a lower unadjusted success rate after AF ablation, despite the fact that ablation procedures and patients were of lower risk compared with MV and HV centres. On the other hand, adjusted overall complication and recurrence rates were non-significantly different among different volume centres, a fact reflecting the heterogeneity of patient and procedural profiles, and a counterbalance between expertise and risk level among participating centres.

AimThe purpose of this study was to compare sex differences of atrial fibrillation (AF) catheter ablation (CA) and to analyse the opportunities for improved outcomes.Methods and resultsAll data were collected from the Atrial Fibrillation Ablation Long-Term registry, a prospective, multinational study conducted by the ESC-EORP European Heart Rhythm Association (EHRA) under the EURObservational Research Programme (ESC-EORP). A total of 104 centres in 27 European countries participated. Of 3593 included patients, 1146 (31.9%) were female. Female patients were older (61.0 vs. 56.4 years; P ConclusionFemales underwent CA procedures for AF less frequently than males throughout Europe, despite more recurrent symptoms. With the same success rate, severe acute complications remained considerable in females, especially in less experienced centres.

International audience; Aims: Cardiomyopathies are a heterogeneous group of disorders that increase the risk for atrial fibrillation (AF). The aim of the study is to assess the prevalence of AF, anticoagulation management, and risk of stroke/transient ischaemic attack (TIA) in patients with cardiomyopathy.Methods and results: Three thousand two hundred eight consecutive adult patients with cardiomyopathy (34.9% female; median age: 55.0 years) were prospectively enrolled as part of the EURObservational Research Programme Cardiomyopathy/Myocarditis Registry. At baseline, 903 (28.2%) patients had AF (29.4% dilated, 27.5% hypertrophic, 51.5% restrictive, and 14.7% arrhythmogenic right ventricular cardiomyopathy, P < 0.001). AF was associated with more advanced New York Heart Association class (P < 0.001), increased prevalence of cardiovascular risk factors and co-morbidities, and a history of stroke/TIA (P < 0.001). Oral anticoagulation was administered in 71.7% of patients with AF (vitamin K antagonist: 51.6%; direct oral anticoagulant: 20.1%). At 1 year follow-up, the incidence of cardiovascular endpoints was as follows: stroke/TIA 1.85% (AF vs. non-AF: 3.17% vs. 1.19%, P < 0.001), death from any cause 3.43% (AF vs. non-AF: 5.39% vs. 2.50%, P < 0.001), and death from heart failure 1.67% (AF vs. non-AF: 2.44% vs. 1.31%, P = 0.033). The independent predictors for stroke/TIA were as follows: AF [odds ratio (OR) 2.812, P = 0.005], history of stroke (OR 7.311, P = 0.010), and anaemia (OR 3.119, P = 0.006).Conclusions: The study reveals a high prevalence and diverse distribution of AF in patients with cardiomyopathies, inadequate anticoagulation regimen, and high risk of stroke/TIA in this population.

Aims The ESC EORP EHRA Atrial Fibrillation (AF) Ablation Long-Term registry was designed to assess management and outcomes of AF catheter ablation procedures in Europe. To investigate the current ablation approaches and their outcomes for patients with paroxymal AF (PAF) and non-PAF in Europe. Methods and results Data from index ablations were collected in 27 European countries at 104 centres in a prospective fashion. Pre-procedural, procedural, and 1-year follow-up data were captured on a web-based electronic case record form. Data on the ablation procedure were available for 3446 patients. Of these, 2513 patients and 933 patients underwent pulmonary vein isolation (PVI) or PVI plus (PVIplus) additional ablation, respectively. The ablation strategy was limited to PVI in 81% and 56% of patients in the PAF and non-PAF group, respectively (P Conclusion In patients with PAF and non-PAF, the ablation strategies of PVI and PVIplus led to similar arrhythmia-free survival rates after 1 year. A considerable hospital readmission rate was noted.

[Abstract] Aim. To investigate the characteristics long-term prognostic implications (up to ∼2.2 years) of atrial fibrillation (AF) compared to sinus rhythm (SR), between acute and chronic heart failure (HF) with reduced (HFrEF

BackgroundThe clinical significance of 16p13.11 duplications remains controversial while frequently detected in patients with developmental delay (DD), intellectual deficiency (ID) or autism spectrum disorder (ASD). Previously reported patients were not or poorly characterised. The absence of consensual recommendations leads to interpretation discrepancy and makes genetic counselling challenging. This study aims to decipher the genotype–phenotype correlations to improve genetic counselling and patients’ medical care.MethodsWe retrospectively analysed data from 16 013 patients referred to 12 genetic centers for DD, ID or ASD, and who had a chromosomal microarray analysis. The referring geneticists of patients for whom a 16p13.11 duplication was detected were asked to complete a questionnaire for detailed clinical and genetic data for the patients and their parents.ResultsClinical features are mainly speech delay and learning disabilities followed by ASD. A significant risk of cardiovascular disease was noted. About 90% of the patients inherited the duplication from a parent. At least one out of four parents carrying the duplication displayed a similar phenotype to the propositus. Genotype–phenotype correlations show no impact of the size of the duplicated segment on the severity of the phenotype. However, NDE1 and miR-484 seem to have an essential role in the neurocognitive phenotype.ConclusionOur study shows that 16p13.11 microduplications are likely pathogenic when detected in the context of DD/ID/ASD and supports an essential role of NDE1 and miR-484 in the neurocognitive phenotype. Moreover, it suggests the need for cardiac evaluation and follow-up and a large study to evaluate the aortic disease risk.

A strategy based on targeted gene panel sequencing identifies possibly pathogenic variants in fewer than 20% of cases in early-onset and familial form of dystonia. By using Whole Exome Sequencing (WES), we aimed to identify the missing genetic causes in dystonic patients without diagnosis despite gene panel sequencing.WES was applied to DNA samples from 32 patients with early-onset or familial dystonia investigated by sequencing of a 127 movement disorders-associated gene panel. Dystonia was described according to the familial history, body distribution, evolution pattern, age of onset, associated symptoms and associated movement disorders. Rate of diagnoses was evaluated for each clinical feature.We identified causative variants for 11 patients from 9 families in CTNNB1, SUCLG1, NUS1, CNTNAP1, KCNB1, RELN, GNAO1, HIBCH, ADCK3 genes, yielding an overall diagnostic rate of 34.4%. Diagnostic yield was higher in complex dystonia compared to non-complex dystonia (66.7%-5.9%; p 0.002), especially in patients showing intellectual disability compared to the patients without intellectual disability (87.5%-16.7%; p 0.002).Our approach suggests WES as an efficient tool to improve the diagnostic yield after gene panel sequencing in dystonia. Larger study are warranted to confirm a potential genetic overlap between neurodevelopmental diseases and dystonia.

Objective To evaluate continuing stiripentol treatment in adulthood in Dravet syndrome (DS). Method Longitudinal data were collected from the last visit prior to age 15 years (V15 y ) to the last visit in adulthood (Vadult ) in the 40 DS patients (32 typical, eight atypical) of a French historical cohort (Paris) of subjects who continued stiripentol from childhood or adolescence to adulthood. Results At Vadult (18-40 years, median = 23 years), all the patients were still receiving stiripentol (exposure = 3-24 years, median = 18 years), associated with clobazam (40/40), valproate (39/40), and topiramate (21/40). Between V15 y and Vadult , stiripentol was interrupted in five patients (two for adverse events) but reintroduced following seizure aggravation. Loss of appetite affected 15 of 40 patients but resolved after reducing the dose of stiripentol or valproate; no other new stiripentol-related adverse events were reported. Mean stiripentol dose was progressively decreased from 39 to 25 mg/kg/d (P = 0.0002), whereas clobazam (0.27 mg/kg/d) and valproate (14 mg/kg/d) remained stable. At Vadult , 37 of 40 patients still had generalized tonic-clonic seizures, but none still had status epilepticus (vs three at V15 y ) and only one had myoclonia. During adulthood, generalized tonic-clonic seizure frequency and duration continued to decrease (P = 0.02, P = 0.008) and 10 patients experienced seizure-free periods ≥ 1 years (up to 5 years). All patients already had intellectual disability at V15 y , but retardation was more severe at Vadult (P = 0.03). Furthermore, neurological/gait condition had declined (two patients became bedridden) and behavior had worsened (P 15 years) and the DS patients treated from adult age or stiripentol-naive subjects reported in the literature. Significance The efficacy and safety of the stiripentol/valproate/clobazam combination started at pediatric age are maintained at very long term during adulthood. Such prolonged stiripentol therapy tends to positively impact the late prognosis of epilepsy, especially when initiated before adolescence.

The current study evaluates and compares the stability of anaerobic digestion of Brewery Spent Grains (BSG) with and without addition of nutrients. Based on the composition of the BSG two levels of nutrients addition were defined. Control reactor, without addition of nutrients, showed signs of instability after 3months of operation and collapsed. On the contrary, supplemented reactors led to a COD removal rate of 60% and a methane production of 280NLCH4.kg-1 VSadded. According to these results, it was possible to define an additive solution adapted to BSG degradation.

Aim Chronic ischaemic cardiovascular disease (CICD) remains a leading cause of morbidity and mortality worldwide. The CICD Pilot Registry enrolled 2420 patients across 10 European Society of Cardiology countries prospectively to describe characteristics, management strategies and clinical outcomes in this setting. We report here the six-month outcomes. Methods and results From the overall population, 2203 patients were analysed at six months. Fifty-eight patients (2.6%) died after inclusion; 522 patients (23.7%) experienced all-cause hospitalisation or death. The rate of prescription of angiotensin-converting enzyme inhibitors, beta-blockers and aspirin was mildly decreased at six months (all P Conclusion In this contemporary European registry of CICD patients, the rate of severe clinical outcomes at six months was high and was influenced by age, heart rate and comorbidities. The medical management of this condition remains suboptimal, emphasising the need for larger registries with long-term follow-up. Ad-hoc programmes aimed at implementing guidelines adherence and follow-up procedures are necessary, in order to improve quality of care and patient outcomes.