Abstract Background Myocardial work (MW) is an innovative tool, which combines global longitudinal analysis with non-invasively assessed ventricular pressure to provide a measure of ventricular performance. This technique has recently been used in subpulmonary right ventricle (spRV), but it has not yet been studied in systemic right ventricle (sRV). Methods and Results MW indexes were obtained from ventricular pressure–strain loops in 48 patients with sRV (32 transposition of the great arteries following atrial switch repair and 16 congenitally corrected transposition of the great arteries; mean age 38.5±10years; 56% male) and in 20 healthy volunteers, as a control group of spRV. Echocardiographic parameters and global longitudinal strain(GLS) analysis demonstrated impaired systolic function in the sRV group (TAPSE: 12.3±3mm, S wave:6.9±2cm/s, fractional area change:29[23-35]% , GLS: -13.4±3%, RV septum GLS: -12±4%, RV free-wall GLS: -14.8±4%). Accordingly, MW indexes were below normal reference values reported for the left ventricle (global work index (GWI): 1056±331 mmHg%; global constructive work (GCW): 1490±269 mmHg%); and global wasted work (GWW) and global work efficiency (GWE) were mildly increased (245.5±162mmHg% and 87±9%, respectively). In addition, sRV free-wall contributed more than the septum to the global performance (GWI septum 879±318, free-wall 1241±412 mmHg%, p<0.0001; GCW septum 1348±287, free-wall 1626±377 mmHg%, p<0.0001). Notably, segmental pressure–strain loops demonstrated higher wasted work values in dyssynchronous segments (figure). As shown in Table1, MW indexes of performance were significantly higher in sRV compared to spRV (spRV GWI:349.3±99mmHg%; p<0.0001; spRV GCW: 451.1±104mmHg%; p<0.0001), likely reflecting sRV adaptation to increased afterload. However, as a response to chronic exposure to systemic pressure, a significant raise of both GWW and GWE in sRV compared to spRV was found (spRV GWW:43.1±22mmHg%, p<0.0001; spRV GWE:92.4±4,p=0.0005). Conclusion Assessment of MW in patients with a sRV is feasible and may provide additional data on ventricular global and segmental performance and efficiency, reflecting sRV adaptation to systemic loading.Table 1

Abstract Background Patients with repaired Tetralogy of Fallot (rToF) present anatomic and hemodynamic sequelae which may impact the right heart mechanics. Right ventricular adaptation to prolonged loading conditions should not be considered in isolation from the right atrium, because the atrial function affects that of the ventricle. Purpose This study aims to describe the right atrial performance using the echocardiographic right atrial longitudinal strain in a population of adult patients with rToF. Methods Echocardiographic images of adult patients (>18 years old) with rToF were retrospectively reviewed, and atrial reservoir (rRAS), conduit (cRAS), and contractile (aRAS) right atrial longitudinal strain were calculated. A group of healthy subjects (CTR) with comparable sex, age, and body surface area was included for comparison. Invasive cardiac catheterization data were also collected for patients with rToF. Results Sixty patients were included in the study: 30 with rToF (age 34 ± 9 years old) and 30 healthy subjects (age 34 ± 11 years old). Patients with rToF presented a lower value of rRAS, cRAS, and aRAS when compared to CTR (rRAS: rToF 20.83 ± 8.44% vs CTR 36.22 ± 9.53%, p<0.0001; cRAS: rToF -11.22 ± 6.41% vs CTR -22.67% ± 8.88%, p<0.0001; aRAS: rToF 9.67 ± 5.94% vs CTR 14.28 ± 6.35%, p=0.03). rRAS presented a good positive correlation with systolic peak velocity at tissue doppler imaging (p=0.006) and a trend toward positive correlation with right ventricle global longitudinal strain (p=0.08) and with the tricuspid annular plane systolic excursion (p=0.07). No correlation was found between invasive right ventricle end-diastolic and -systolic pressure and echocardiographic right atrial longitudinal strain parameters. Conclusion Adult patients with rToF presented a lower value of right atrial longitudinal strain, indicating an impaired atrial performance. Right atrial longitudinal strain provides additional insight for the comprehensive evaluation of right heart mechanics and should be systematically evaluated during the follow-up of adult patients with rToF.

Abstract Background Sodium-glucose Cotransporter-2(SGLT2) inhibitors are currently recommended as first line therapy for all patients with heart failure with reduced ejection fraction (HFrEF).Adults with a systemic right ventricle (sRV) may develop progressive systolic dysfunction during follow-up. Optimal medical therapy for HFrEF remains still to be determined in this complex population. Purpose We aimed to assess safety and evaluate potential clinical benefit of dapagliflozin in patients with a sRV compared to standard medical treatment for HF. Methods Inclusion criteria were:age ≥ 18 years; transposition of the great arteries (TGA) following Senning/Mustard repair or congenitally corrected TGA, sRV EF ≤ 40%, already on optimized medical therapy including sacubitril/valsartan for at least 3 months. Exclusion criteria were: systolic blood pressure (SBP) <90 mmHg, glomerular filtration rate (GFR)<30ml/min and univentricular physiology. All eligible patients attending our tertiary center for adult congenital heart disease were randomly assigned to the treatment or control group. Patients in the treatment arm were prescribed 10 mg dapagliflozin o.d. on top of their medical therapy, while control group continued standard therapy. Patients were scheduled for a structured follow-up including clinical evaluation, blood test, echocardiography, and 6 minute-walking at 6 months from study inclusion for both groups. Results Fifty patients (41±11 years, 54% male, 64% TGA) met the inclusion criteria: 25(50%) were started on 10 mg dapagliflozin. There was no significant difference in terms of age (p=0.4), sex(p=0.1), anatomy(p=0.2) and baseline sRV EF (p=0.2). Up to February 2023, 14 patients in the treatment group and 13 controls completed the 6-month follow-up. Clinical and echocardiographic findings at baseline and at 6-month in the treatment group are summarized in Table1: dapagliflozin was well tolerated and no major adverse events were reported. Treatment did not impact on the systolic blood pressure and renal function. However a significant improvement in the sRV freewall global longitudinal strain(GLS) was found (-15.8±3 Vs -18.3±3; p=0.03). Differences in main echocardiographic indices of sRV systolic function between baseline and follow-up in the two arms are shown in Table2: treatment resulted in significant positive changes of sRV FAC, GLS, and free wall GLS compared to the group on standard therapy. Conclusions Initial results from the ongoing single-centre DAPA-SERVE trial provided reassuring data on the safety profile of dapagliflozin in patients with a sRV. Furthermore, significant improvement of echocardiographic indices of sRV function in patients on dapagliflozin compared to those on standard medical therapy was demonstrated at 6-month. Longer follow-up is warranted to determine the clinical impact of those positive changes and to shed light on the potential benefit of SGLT2 inhibitors use on top of standard therapy in this complex population.

Background: Cystic fibrosis is the most common hereditary recessive disease with an incidence of about 1:2500/ 3000. It has long been known that the disease is caused by deleterious mutations in the CFTR gene. Conven-tionally, the disease is diagnosed in several phases. The analysis of all the possible disease-causing molecular alterations is time consuming and may not lead to a definitive diagnosis in several cases. Consequently, we propose, in this paper, a rapid sequencing method that, in a single procedural asset, reveals the presence of small mutations and also the copy number variants (CNVs) from the DNA extracted from the Guthrie Spot. Materials and Methods: We first sequenced 30 blood spots, then we validated the method on 100 spots that un-derwent both traditional analyses and this complete NGS sequencing, and lastly, we tested the strategy on pa-tients who normally do not reach the molecular sequencing step because of low level of Immune-Reactive Trypsinogen. Results: Using this procedure, we identified 97 variants in the CFTR gene of our samples and 6 CNVs. Notably, the significant data were obtained in the group of patients with borderline or negative IRT who routinely would not undergo molecular testing. We also identified 6 carriers of "disease-causing" variants. Conclusion: This method is very robust. Indeed, there was a 100% concordance with Sanger sequencing vali-dation, and 6 mutation carriers were identified who normally escaped molecular testing with actual conventional procedure. There were also 3 duplications of almost the entire gene in heterozygosity, which were not seen with traditional methods. Being quick and easy to perform, we suggest that complete sequencing of the CFTR gene, as in this study be considered for all newborns.

Abstract Background Adults with congenital heart disease (ACHD) are a vulnerable population. Routine vaccination is the only strategy to prevent a life-threatening infection. However, concerns on the cardiac safety and efficacy of COVID-19 vaccines have been raised. Aim To assess safety and efficacy of available COVID-19 vaccines in ACHD patients. Methods Data on COVID-19 infection and vaccines including booster doses and any suspected or confirmed adverse events were prospectively collected for all ACHD patients attending our tertiary centre from the beginning of the vaccination campaign (March 2021). A group of 75 healthy volunteers, matched per age and sex, was included for comparison. Antispike IgG titre was routinely obtained at the ACHD clinic. Patients' attitude towards COVID-19 was explored with a questionnaire. Results As of February 2022, 498 ACHD patients (36.7±16 years, 54% male,69% with moderate-complex defects, 48% with advanced physiological stage) were enrolled. Four hundred and sixty-one (92%) were fully vaccinated: the type of vaccine was Pfizer-BioNTech for 399 (86%) patients, Moderna for 20 (4%) and AstraZeneca for 26 (6%), 9 received a mixed vaccine regimen (2%). Forty-two (9%) had a history of previous COVID-19 infection and therefore received only one dose. Two-hundred and sixty-nine (58%) patients received a booster dose. Adverse events were mainly mild and transient. One patient complaining of chest pain following administration of mRNA-based vaccination was diagnosed with acute pericarditis, which made full remission after appropriate therapy. Two patients reported a non-specific increment of inflammatory markers. No other severe adverse events were reported. Thirty-seven (7%) refused COVID-19 vaccination being scared of potential cardiac/extra-cardiac adverse events. Among those not-vaccinated, 9 (24%) had a history of previous mild COVID-19 infection. IgG titre was measured in 243 patients at 1915 [835–5934] BAU/ml, which was significantly higher compared to controls (1196 [827–2048] BAU/ml, p=0.002). Three ACHD patients contracted COVID-19 infection after the first dose, while 65 (14%) fully vaccinated patients tested positive for COVID-19, all with mild to moderate symptoms. COVID-19 symptoms duration was significantly longer in case of infection before vaccination (10 [2.7–15] vs 3 [1.2–7], p=0.03). One Fontan patient was tested positive for COVID-19 twice, before and after COVID-19 vaccination, requiring hospitalization in both cases. Four hundred and seven patients completed the questionnaire: 128 (31%) declared to be scared of potential cardiac effects of the vaccine and that the discussion with the ACHD cardiologist was crucial to decide to undergo COVID-19 vaccination. Conclusions Our data provide real-world evidence on COVID-19 vaccines safety and efficacy in ACHD patients. Patients' education from the ACHD team may play a key role in vaccine acceptance in this vulnerable population. Funding Acknowledgement Type of funding sources: None.

Abstract Funding Acknowledgements Type of funding sources: None. Background Adults with coarctation of the aorta (CoA) may present residual aortic obstruction and develop arterial vasculopathy and subclinical left ventricular (LV) dysfunction. Myocardial work (MW) is a novel non-invasive index of myocardial efficiency calculated from echocardiographic LV pressure-strain loops, which yields incremental information over ejection fraction and global longitudinal strain. (GLS) Purpose Aim of the present study is to analyze LVMW in a cohort of adult patients with operated aortic CoA Methods CoA patients aged > 18 years who underwent transthoracic echocardiography between September 2020 and July 2021 at our tertiary centre were included. Exclusion criteria were significant recoarctation, impaired LVEF, significant valvular disease and suboptimal image quality. A group of healthy individuals with no cardiac abnormalities. GLS and peak strain dispersion(PSD) were measured. MW indices were calculated using the blood pressure measured in the right arm at the time of the exam. Results Sixty patients (26[22-33]years, 66%male) were included. Data on previous medical history, clinical status at last assessment and Coa-related echocardiographic findings are showed in table 1. No significant differences in traditional parameters of LV systolic and diastolic function were found between groups (EF 60[57-64] vs 57[53-61],p = 0.6), however Coa patients had higher LVmass (84[75-97] vs 68[56-75]g). GLS and MW indices in the study population and in the control group are reported in table 2. Coa group showed lower GLS values and higher PSD (p < 0.0001 for both). Global work index(GWI) and global constructive work(GCW) values were not significantly different between groups, whereas CoA group showed significant increase of global wasted work(GWW) and impaired global work efficiency(GWE,p = 0.003 and 0.0005 respectively). Spearman’s linear method illustrated that both GCW and GWI had a moderate positive relation with mean gradient across the descending aorta at continuous wave Doppler. PSD was positively related to GWW and inversely related to GWE(Figure 1). Using linear regression model with the log of GWE values as dependent variable,PSD,age(β:-0.002,p = 0.03) and LVmass(β:-0.06,p = 0.004)were related to GWE. However, only PSD retained a significant relation on multivariable analysis(β:-0.002,p > 0.0001). Conclusion MW indices assessment is feasible in Coa patients may provide a more comprehensive understanding of the overall myocardial mechanics and performance. In particular, MW demonstrated impaired LV efficiency, which was strongly related to increased mechanical dispersion in Coa patients. Abstract Figure. Abstract Figure.

Abstract Funding Acknowledgements Type of funding sources: None. Background Blood speckle imaging (BSI) is a new speckle-tracking-based technique for the evaluation of blood flow. Ventricular flow vortices have been studied in sinus rhythm in normal and dysfunctional hearts, however, data are lacking in patients with Kent accessory pathway (KAP) and short atrio-ventricular (AV) conduction. Purpose We aimed to evaluate the characteristics of left ventricle blood vortices in children with KAP. Methods Nineteen paediatric patients (age 7 ± 2.9 years) were included in the study: 13 patients with manifest KAP (KAP group) and 6 age and sex -matched controls with normal AV conduction (CTR group). A thorough echocardiographic evaluation with 2D, color doppler and BSI was performed in all the included patients. BSI was recorded in apical 3-chamber view with a 6S-D probe. Vortices characteristic were analysed during filling phase of the left ventricle. We focused on the anterior vortex generated by mitral valve, which persisted longer during the cardiac cycle and is assumed to contribute to optimizing cardiac function. A standard 12-lead ECG was also recorded for each child in KAP group to esteem KAP localization. Results According to Arruda criteria for KAP localization, all patients in KAP group manifested the accessory pathway in the septal region. All patients in CTR group presented one major anterior vortex during filling phase, while in KAP group 10 patients out of 13 (p= 0.009) lacked of this main anterior vortex, showing instead fragmented different vortices. There were no differences in term of left ventricle function (KAPg 59.8 ± 4.02% vs CTRg 59.0 ± 2.5%, p= 0.6) and global longitudinal strain (KAPg -18.6 ± 1.0% vs CTRg -19.6 ± 3.1%, p= 0.5) between the two groups. Conclusion In our preliminary analysis, in patients with septal KAP, blood vortices adapted their diastolic traces to the septal dyssynchrony showing a fragmented pattern. We speculate this fragmentation may contribute to impair the performance of the left ventricle. Abstract Figure. BSI in control vs patient with WPW

Abstract Background Sacubitril/valsartan has been shown to reduce mortality and morbidity inpatients with heart failure and reduced systolic function. However, the effects of this novel association in patients with congenital heart disease and a systemic right ventricle (sRV) have not been investigated yet. Purpose We aimed to assess tolerability and efficacy of sacubitril/valsartan in patients with a sRV Methods From September 2020 to March 2021, 38 patients with congenitally corrected transposition of the great arteries or transposition of the great arteries after Senning or Mustard repair were prospectively enrolled. Inclusion criteria were: age ≥18 years, optimal medical therapy including ACEi/ARB for at least 6 months and EF of the sRV ≤40%. Patients with univentricular physiology, systolic blood pressure (SBP) <90mmHg, glomerular filtration rate (GFR) <30ml/min or K >5.5mEq/L were excluded. RV systolic function was assessed on echocardiography using a multiparametric evaluation. The study protocol contemplates serial assessments at 1, 3, 6 and 12 months after treatment initiation. Results Up to March 31th, 23 patients completed 1-month and 15 completed 3-month assessment after treatment initiation. Baseline patients' characteristics are summarized in table 1. The medication dose was up-titrated to the highest tolerated dose during follow-up. During early follow-up, no major adverse events were reported. Treatment did not impact significantly on the values of serum potassium (basal K+ 4.4 [4.2–4.6] mEq/L, K+ at 3 months 4.4 [4.3–4.6] mEq/L, p=0.7) and GFR (basal GFR 113.9±35ml/min, GFR at 3 months 107.8±21 ml/min, p=0.7). Although SBP did not change significantly (114±12 vs 113.9±19 mmHg at 1-month and 117.3±12 mmHg at 3 months; p=0.9 for both), 2 (5%) patients ceased the treatment due to symptomatic hypotension during the first month of treatment. There was no significant change in the NYHA class. However, the 6-minute walking distance increased significantly after 3 months (365±120 vs 498.3±71 min; p=0.01). Furthermore, while traditional echocardiographic parameters of RV systolic function (TAPSE, s wave and FAC) did not change significantly, RV global longitudinal strain (GLS) and RV free wall GLS demonstrated subclinical improvement in right ventricular systolic function (table 2). Conclusions Our short-term results from an ongoing prospective study showed that sacubitril/valsartan is well tolerated in patients with a sRV with early evidence of improvement in exercise tolerance and sRV systolic function. Longer follow-up is warranted to confirm these data. Funding Acknowledgement Type of funding sources: None. Table 1Table 2

s / Atherosclerosis 245 (2016) e243ee251 e247 the degree of atherosclerosis in monogenic FH patients versus polygenic individuals with hypercholesterolaemia. Method: Carotid Intima Media Thickness (cIMT) was measured by B-mode ultrasound in three different segments of carotid arteries (common carotid artery, bulb and internal carotid artery) in 86 individuals (53 female and 33 male) with a clinical diagnosis of FH (LDL-Cmean+SD: 5.8 ± 1.3mmol/l). 56 patients had monogenic FH with a known mutation in the LDLR or APOB gene and 30 patients had no mutation but they had a score in the top two quartiles of a six LDL-C-raising SNPs gene score. Results: The monogenic patients were younger than polygenic individuals (50 ± 14 years vs 57 ± 12 years, p 1⁄4 0.03). There was no significant difference in total cholesterol level, LDL-C and HDL-C between the two groups. Triglyceride level was significantly higher in polygenic compared to monogenic group [1.6 ± 0.7 mmol/l vs 1.2 ± 0.5 mmol/l, p 1⁄4 0.01]. After adjustment for age and gender, the mean of all the cIMT measurements was significantly higher in monogenic than polygenic patients [0.74 mm (0.7e0.79) vs 0.66 mm (0.61e0.72), p 1⁄4 0.03]. Conclusion: The severity of atherosclerosis as measured by cIMT is higher in monogenic FH individuals than the polygenic group. While LDL-C levels need to be reduced in both groups, the greater degree of carotid atherosclerosis supports aggressive management of their LDL-C levels with potent statins and other LDL-C lowering modalities in combination. Referred to specialist care 48 (77%) GP managing patient 3 (5%)

Aims: Familial Hypercholesterolemia (FH) is a genetic disease caused by a reduced LDL cholesterol catabolism, high blood concentration, tissues and vessels cholesterol deposits and early cardiovascular disease. Heterozygous condition occurs in about 1/500 individuals. Most of the affected children in Italy are undiagnosed. A simple blood test can early detect most kids with FH and could allow a global therapeutic approach to delay or perhaps prevent artery plaques. The aim of the study is to realize a screening program model for all pediatricians.

BACKGROUND:Allergic sensitization in children and allergic diseases arising therefrom are increasing for decades. Several interventions, functional foods, pro- and prebiotics, vitamins are proposed for the prevention of allergies and they can't be uncritically adopted.OBJECTIVE:This Consensus document was developed by the Italian Society of Preventive and Social Paediatrics and the Italian Society of Paediatric Allergy and Immunology. The aim is to provide updated recommendations regarding allergy prevention in children.METHODS:The document has been issued by a multidisciplinary expert panel and it is intended to be mainly directed to primary care paediatricians. It includes 19 questions which have been preliminarily considered relevant by the panel. Relatively to each question, a literature search has been performed, according to the Italian National Guideline Program. Methodology, and a brief summary of the available literature data, has been provided. Many topics have been analyzed including the role of mother's diet restriction, use of breast/formula/hydrolyzed milk; timing of introduction of complementary foods, role (if any) of probiotics, prebiotics, vitamins, exposure to dust mites, animals and to tobacco smoke.RESULTS:Some preventive interventions have a strong level of recommendation. (e.g., the dehumidifier to reduce exposure to mite allergens). With regard to other types of intervention, such as the use of partially and extensively hydrolyzed formulas, the document underlines the lack of evidence of effectiveness. No preventive effect of dietary supplementation with polyunsaturated fatty acids, vitamins or minerals has been demonstrated. There is no preventive effect of probiotics on asthma, rhinitis and allergic diseases. It has demonstrated a modest effect, but steady, in the prevention of atopic dermatitis.CONCLUSIONS:The recommendations of the Consensus are based on a careful analysis of the evidence available. The lack of evidence of efficacy does not necessarily imply that some interventions may not be effective, but currently they can't be recommended.

Aim of the study was to explore the response to a fluid challenge test (FCT) in normal subjects and in patients with pulmonary hypertension (PH). 168 subjects underwent right heart catheterization in basal conditions and after FCT. At baseline, 50 subjects showed normal pressures (healthy controls

Background: The differential diagnosis between pre-and postcapillary pulmonary hypertension (PH) is of major therapeutic relevance and thus requires optimal clinical probability assessment with echocardiography.Methods: We prospectively analyzed 152 consecutive patients referred to a PH center over a 1-year period undergoing quasi-simultaneous (within 1 hour) echocardiography and right heart catheterization. Echocardiography was performed as usually recommended for the assessment of PH and left heart conditions. PH was defined as a mean pulmonary artery pressure 25 mm Hg. Postcapillary PH was diagnosed on the basis of a pulmonary capillary wedge pressure >15 mm Hg.Results: Ten of 152 patients (7%) had no PH, 81 of 152 (53%) had precapillary PH, and 61 of 152 (40%) had postcapillary PH. The following five echocardiographic variables were found to predict precapillary PH: right heart chamber larger than the left (P = .0018), left ventricular eccentricity index > 1.2 (P = .0039), dilated inferior vena cava without inspiratory collapse (P = .0076), E/e' ratio <= 10 (P = .00001), and the right ventricle forming the heart apex (P = .0144). Beta coefficients from multiple logistic regression were significant for dilated inferior vena cava without inspiratory collapse (P = .0464) and E/e' ratio <= 10 (P = .0002). The score based on beta coefficients, ranging from 3 to 34 points, resulted in optimal discrimination at >5, with a positive predictive value of 67.9% and a negative predictive value of 77.5% for precapillary PH.Conclusion: Echocardiography enables a clinically satisfactory differential diagnosis between pre-and postcapillary PH.

Liver abnormalities that normalize during infancy as well an enteropathy are reported in Shwachman-Diamond syndrome (SDS). The pathogenesis of both conditions is unknown. We report two SDS cases with autoimmune-like (antismooth muscle and/or antinuclear antibody positivity) liver disease and antigliadin antibody positive inflammatory enteropathy. Hypertransaminasemia did not resolve after immunosuppressive therapy and/or a gluten-free diet. These transient autoimmune phenomena and gut-liver axis perturbations may have played a role in transient SDS hepatopathy and enteropathy. Our report may stimulate other studies to define the relationship between the SDS genetic defect and intestinal permeability as the pathogenic mechanism underlying SDS related liver and intestinal inflammation.

Very few data are available on pediatrics malpractice claims.We report the first data obtained in Italy on pediatrics regarding a wide population study during a 8 years survey.Data concerning 164 claims are presented and discussed.Our data suggest how big is the problem and they may be helpful to face it.