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History of presentation A 76–year–old woman presented to our EchoLab for worsening exertional dyspnea. Few weeks prior the patient underwent cardiological examination that showed heart failure with preserved ejection fraction (HFpEF) with bilateral pleuric effusion, severe mitralic regurgitation (MR), moderate tricuspid regurgitation (TR) with an estimated systolic pulmonary artery pressure (sPAP) of 50 mmHg and a mildly increased mean gradient on bioprothesic aortic valve (26 mmHg). Past medical history The patient had a medical history significant for arterial hypertension, hyperlipidemia, diabetes mellitus, permanent atrial fibrillation and HCV–related liver disease. She received double surgical aortic valve replacement in 2015 and 2019, the second procedure was complicated by intraoperatory stretching of mitral anterior leaflet and atrioventricular block treated with implantation of bicameral PMK. In the following weeks, the patient was admitted to hospital for exposure of the PMK generator pocket associated to catether cultures positivity for S. Aureus oxacilline–resistant, thus undergoing to device removal and positioning of a new PMK. Investigations The cardio–thoracic auscultation revealed a bilateral basal reduction of vesicular breath sounds, an apical sweet systolic murmur (suggestive of MR) and a systolic small aortic murmur best heard at the second intercostal space. The transthoracic echocardiography showed a blood flow apparently originating from interatrial septum heading towards the free left atrial wall. The Transoesophageal Echocardiography (TEE) with bubble test ruled out any interatrial communication. The 3D TEE acquisitions clarified that the shunt arose from the left ventricular outflow tract (LVOT), thus allowing the diagnosis of fistula between the LVOT and the left atrium. Follow–up and conclusions The patient underwent a procedure of percutaneous closure of the fistula. One month after this intervention, the patient presented to our department for the cardiological follow–up. We noticed that the closure had been successful with no left residual shunts and a reduction of the transprothesic mean aortic gradient (18 mmHg). This case report highlights the importance of the 3D echocardiography in order to settle uncertain diagnostics whereas the 2D echocardiography alone is not sufficient. Nevertheless, the diagnostic challenge that remains open is to understand whether the etiology of the fistula is iatrogenic or post–infectious.

Patients with history of atrial fibrillation (AF) undergoing mitral edge–to–edge repair procedure with Mitraclip tend to be relatively older, have more advanced valve disease, and suffer from more comorbidities than patients without AF [1;2]. Moreover, their all–cause mortality rate one year after the procedure and hospitalization rate for heart failure is higher than that of patients in sinus rhythm [3]. Therefore, managing patients with AF poses a greater challenge, and their prognosis is considerably worse. Improvement of mitral regurgitation following mitral edge–to–edge repair procedure with Mitraclip may reduce atrial volume overload positively impacting AF triggers. In this report, we present a case of spontaneous restoration of stable sinus rhythm in a patient with chronic AF undergoing mitral valve repair procedure with Mitraclip. The patient, 80 years old, underwent implantation of a clip on centro–lateral site of the mitral valve plane (A2–P2) with mild residual insufficiency and an optimal procedural result. The restoration of sinus rhythm, which occurred during the first hours after the procedure, proved to be stable at the 30th day control post–discharge. the indexed left atrial volume remained unchanged (LAVI 43–45 mL/m2). Literature on the frequency of spontaneous sinus rhythm restoration following edge–to–edge mitral repair with Mitraclip in patients with chronic AF is limited. In a sub–analysis of the COAPT study [4], in addition to the known benefits of the Mitraclip procedure, it was possible to highlight a significant reduction in the rate of stroke in patients with AF. This outcome could be attributed to the reduction of the AF burden associated with mitral valve insufficiency. More studies are although necessary to determine the procedure‘s impact in this specific clinical situation. Rreferences: [1] Velu JF, Am J Cardiol. 2017 Dec 1;120(11):2035–2040. [2] Saad AM, Catheter Cardiovasc Interv. 2021 May 1;97(6):1252–1256. [3] Shah S, Heart Fail Rev. 2021 May;26(3):531–543. [4] Gertz ZM, Circ Cardiovasc Interv. 2021 Apr;14(4):e010300.

Background Wolf-Parkinson-White Syndrome (WPW) has been associated with reduced local myocardium deformation during systole. According to guidelines, when the left ventricle (LV) dysfunction is present catheter ablation of the accessory pathway may be required, even in asymptomatic patients. Purpose The study aimed to assess the diagnostic value of non-invasive myocardial work in predicting subtle myocardial abnormalities in children with WPW. Methods Eighty pediatric patients (age 7.91±3.2 years) were included in the study: 20 cases with manifest WPW and 60 age- and sex-matched controls (CTR). Global myocardial work index (MWI) was measured as the area of the LV pressure-strain loops. From MWI, global Constructive Work (MCW), Wasted Work (MWW) and Work Efficiency (MWE) were estimated. In addition, standard echocardiographic parameters of LV function were evaluated. Results Patients characteristics are summarized in the table. Despite normal LV EF and GLS, children with WPW had worse MWI (WPW 1292.90±307.67 mmHg% vs CTR 1658.73±241.74 mmHg%, p=0.0000005), MCW (WPW 1844.15±267.96 mmHg% vs CTR 2104.90±237.85 mmHg%, p=0.00009), MWW (WPW 101.5 [85–148.25] mmHg% vs CTR 72 [54.75–109.25] mmHg%, p=0.004) and GWE (WPW 94 [91.75–95] mmHg% vs 96 [95–97] mmHg%, p=0.00012) (table). In the WPW group, MWE (r=−0.6, p=0.009) and MWW (r=0.6, p=0.01) was found to correlate with a prolonged QRS (figure). A multiple regression model was generated to identify the relation between abnormal myocardial work indices (worst interquartile range as dependent variable) and several independent variables. QRS was the best independent predictor of impaired myocardial work. In particular, a QRS>110 msec showed an 86% sensibility and 85% specificity for abnormal MWE (AUC of 0.85), and a 75% sensibility and 83% specificity for abnormal MWW (AUC of 0.83) (figure). Conclusion In children with WPW, myocardial work indices were found significantly reduced, even in presence of normal LV EF and GLS. Prolonged QRS independently predicted myocardial impairment. In pediatric patients with WPW, myocardial work may represent a sensitive measure of LV dysfunction and help in the decision-making. Funding Acknowledgement Type of funding sources: None.

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.

Background Sacubitril/valsartan has been proved to reduce mortality in heart failure and reduced ejection fraction (EF) and is currently recommended as first-line therapy. However, effects in patients with a systemic right ventricle (sRV) have not been systematically investigated yet. Purpose We aimed to assess safety and efficacy of sacubitril/valsartan in patients with a sRV Methods From September 2020 to April 2021, all patients with congenitally corrected transposition of the great arteries (TGA) or TGA after Senning/Mustard repair attending our tertiary centre were prospectively enrolled. Inclusion criteria were: age ≥18 years, 3-months of optimal medical therapy including ACEi/ARB and sRV EF≤40%. Patients with univentricular physiology, systolic blood pressure (SBP) 5.5 mEq/L were excluded. SBP and blood samples were obtained at 1-month of treatment. Other clinical and echocardiographic variables were reassessed at 6 and 12-month follow-up and the medication was progressively up-titrated to the highest tolerated dose. Results Fifty-one patients (38±11 years, 60% male, 34% ccTGA) were included. Up to March 2022, 48 (92%) patients were reviewed after 6 months of therapy and 35 (68%) completed the first year of follow-up. Baseline patients' characteristics are summarized in Table 1. At 1 month, treatment did not impact on the serum potassium values (4.5±0.3 vs 4.4±0.3 mEq/L, p=0.9) and GFR (112±33 vs 112±31 ml/min, p=0.3), while SBP dropped significantly (119±13 vs 108±18 mmHg, p=0.003). Two patients ceased the treatment due to symptomatic hypotension during the first month. One patient developed a nephrotic syndrome at 4 months of follow-up, which was likely unrelated to the treatment. No other major adverse events were reported. One patient was lost to follow-up after 3 months. Despite no significant change in the NYHA class (p=0.9), the 6-minute walking distance increased significantly at 6-month (Table 2). Nt pro BNP values were significantly decreased at 6-month, and returned to baseline at 12-month. Improved sRV systolic function was demonstrated at 6 and 12-month by significant increase in fractional area change, RV global longitudinal strain and sRV EF measured with 3D echocardiography. Conclusions Our mid-term results showed that sacubitril/valsartan is well tolerated in patients with a sRV and leads to signficant improvement of sRV systolic function, supporting its use in this complex population. Funding Acknowledgement Type of funding sources: None.

Background Anthracyclines are essential adjuvant therapies for a variety of cancers, particularly breast, and gastric and esophageal cancers. Whilst prolonging cancer–related survival, these agents can in–duce drug–related cardiotoxicity. Spirulina, Reishi (Ganoderma Lucidum) and Moringa are three nutaceuticals with anti–inflammatory effects that are currently used in cancer patients to improve quality of life and fatigue. Methods Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with short–term doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), Singo at 12 mg/kg (Singo, n=6) or doxorubicin combined to Singo (DOXO–Singo, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100, Fujifilm). Myocardial expression of NLRP3, DAMPs (galectine 3 and calgranulin S100) and 13 cytokines (IL–1α, IL–1β, IL–2, IL–4, IL–6, IL–10, IL–12, IL17–α, IL–18, IFN–γ, TNF–α, G–CSF, and GM–CSF) were quantified through selective mouse ELISA methods. Myocadial fibrosis, necrosis and hypertrophy were analyzed through Immunohistochemistry (IHC). Human cardiomyocytes (HFC cell line) were exposed to subclinical concentration of doxorubicin (200 nM) alone or in combination to Singo ( at 10, 25 and 50 µg/ml) for 24 and 48h. Cell viability studies were performed through MTS assay. Expression of NLRP3 and p65/NF–kB) were made through selective ELISA methods. Results In preclinical models of short–term DOXO cardiotoxicity, Singo improved significantly EF and FS and prevented the reduction of radial and longitudinal strain after 10 days of treatment with DOXO. A reduced expression of myocardial NLRP3 and NF–kB levels in cardiac tissues were seen in DOXO–Singo group compared to DOXO mice (p Conclusion Singo is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. Cardioprotective properties of Singo are mediated by the reduction of lipid peroxidation products and expression of NLRP3–NF–kB –cytokine pathways.

Background Ostium secundum ASD (ASDII) is the most common type of congenital heart disease in adults. Percutaneous closure has emerged as the first–line treatment for the majority of ASDII. However, the occurrence of Pulmonary Hypertension (PH) with combined pre– and post–capillary component may render ASD management challenging in elderly patients. Methods We report the hemodynamic data and clinical findings of elderly patients (> 60 years old) undergoing transcatheter closure of an ASDII at our department. Results From 2000 to 2021, 82 elderly patients were scheduled (mean age 65,4+ 4,4) of which 60 (73%) were female. Systemic arterial hypertension and supraventricular arrhythmias were the most common comorbidities accounting respectively 51% and 38% of cases. The right ventricular overload supported the ASD closure in 76 cases (93%) and paradoxical embolism in the remaining 6 (7%). 17 patients (21%) were in NYHA class III– IV. At right heart catheterization, 33 patients had normal pulmonary arterial pressure and 49 patients showed a mean pulmonary artery pressure > 20 mmhg. In the latter cohort, 33 showed a pulmonary artery wedge pressure (PAWP) 15 mmHg (Group II). The device implantation was completed in all patients except one with elevated pulmonary vascular resistance (PVR) of the Group I. For 14 patients of Group II, balloon occlusion test was required during the catheterization. ASD closure was achieved promptly in 10 patients. However, to reduce the risk of acute pulmonary oedema, in one case we created a small fenestration in the occluder device and in other case we retained the patency of additional defect (both patients exhibiting slightly PAWP increase during balloon occlusion test). In one patient showing significantly PAWP increase during balloon test, delayed ASD closure was performed ensuring the improvement of hemodynamic parameters at 3 months initiation of medical therapy with angiotensin–converting enzyme inhibitor and loop diuretic diuretics. For the remaining 4 patients, the percutaneous closure was not been done because of prohibitive hemodynamic parameters. Overall, ASD closure was performed successfully in 94% of cases. Conclusions Age and comorbidities are not absolute contraindications to ASDII percutaneous closure. In the complex cases, both medical therapies and balloon occlusion test may be use to support the decision–making process.

Background Multifenestrate aneurysms of interatrial septum (ISA) are a challenge in paediatric age, not only for the complex anathomy, but also for small body surface and small dimensions of cardiac chambers of the patients, that may limit the use of large and multiple devices. Aim of the study: to evaluate the efficacy of percutaneous closure of multifenestrate aneurysms during mid–term and long–term follow–up; to evaluate if the morphological characteristics of interatrial septum may influence the success of the procedure. Materials and Methods We retrospectively analyzed 63 patients (mean–age 9,12±3,12 years) undergone to cardiac catheterism from 2000 to 2021, for percutaneous closure of interatrial aneurysm in our division of Cardiology, subdivided into 3 groups on the basis of side and morphological characteristics of the interatrial aneurysm: Group I (2 o more defects DIA>5 mm); Group II (one defect >5 mm and more than one further fenestrations); Group III (multiple fenestrations). Results Percutaneous closure was efficacy in 60 patients (95%), while in 3 patients (5%) surgery closure was necessary. In half of the treated patients (30) we used 2 devices. Complications occurred in 4 patients (6%). Only in 2 patients occurred major complications (Atrio–Ventricular Block that needed PMK implantation and partial displacement of device, treated by removal and percutaneous replanting). Residual shunts, not emodynamically significant appear in the immediate post–operative period in 26% and during the follow–up in 18%. The group I was associated with greater risk of failure of the procedure (P Conclusions Percutaneous closure of multifenestrate aneurysm of interatrial septum in paediatric age are effective and shows low incidence of failure and complications. If is present residual shunt is not significant. The anathomy of interatrial septum influences procedural outcome.

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

Funding Acknowledgements Type of funding sources: None. Background Wolff-Parkinson-White Syndrome (WPW) has been associated with reduced local myocardium deformation during systole. Left ventricle (LV) dysfunction due to electrical dyssynchrony may require catheter ablation of the accessory pathway, even in asymptomatic patients. Purpose The study aimed to assess the diagnostic value of non-invasive myocardial work in predicting subtle myocardial abnormalities in patients with WPW. Methods Forty-four paediatric patients (age 8.2 ± 4.3 years) were included in the study: 12 cases with manifest WPW and 32 age-, sex- and arterial pressure- matched controls (CTR). LV ejection fraction (EF) and global longitudinal strain (GLS) were evaluated. Global myocardial work index (MWI) was measured as the area of the LV pressure-strain loops. From MWI, global Constructive Work (MCW), Wasted Work (MWW) and Work Efficiency (MWE) were estimated. Results Despite normal LV systolic function by standard echocardiographic parameters, patients with WPW had lower MWI (1233.5 ± 281.6 mmHg% in WPW vs 1624.0 ± 305.8 mmHg% in CTR, p = 0.0004), MCW (1833.4 ± 257.9 mmHg% in WPW vs 2069.0 ± 319.9 mmHg% in CTR, p= 0.03), MWW (187.6 ± 117.7 mmHg% in WPW vs 90.9 ± 58.9 mmHg% in CTR, p= 0.0008) and GWE (90.5 ± 4.8% in WPW vs 95.2 ± 2.2% in CTR, p= 0.00006). There were no significant differences in GLS and EF between patients with WPW and controls. Conclusion Myocardial work indices were found significantly reduced in patients with WPW, even in presence of normal LV EF and GLS. In patients with WPW, MWI may represent a sensitive measure of myocardial dysfunction and help in the decision-making for catheter ablation. Abstract Figure. Myocardial work in WPW Abstract Figure. Myocardial work in control patient

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). 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.

Funding Acknowledgements Type of funding sources: None. Background myocardial work (MW) is a novel echocardiographic technique which assesses left ventricular (LV) performance through LV pressure-strain loops. MW corrects speckle tracking echocardiography (STE)-derived parameters for afterload using non-invasive systolic blood pressure (SBP) as a surrogate for LV systolic pressure. In patients with severe aortic stenosis (AS), the corrected MW (cMW) has been proposed, consisting in adding the mean aortic gradient in SBP. This method revealed to be feasible and reliable, demonstrating good correlation with invasively measured LV systolic pressure. Purpose to evaluate myocardial performance of patients with severe AS, before and after transcatheter aortic valve implantation (TAVI), by MW indices. Methods patients with severe AS undergoing TAVI were included. Transthoracic, standard echocardiography and STE were performed the day before the procedure and within 2 days after. MW was calculated by combining STE-derived indices with non-invasively estimated LV systolic pressure. Results 30 patients (79 ± 5 years old, 56% females) with severe AS (mean gradient 47 ± 14 mmHg, aortic valve area 0.6 ± 0.1 cm2), and eligible for TAVI were enrolled. Baseline global longitudinal strain was impaired (GLS -15 ± 4%), in presence of normal LV ejection fraction (LVEF 57 ± 10%). Corrected global work index and global constructive work were preserved at baseline and markedly decreased after TAVI (cGWI 2322 ± 791 vs 1710 ± 505 mmHg%, p = 0.001; cGCW 2774 ± 803 vs 2083 ± 536 mmHg%, p = 0.0007). Corrected global wasted work and global work efficiency were higher than reference values existing in literature, and no significant changes were observed after TAVI (cGWW 276 ± 174 vs 277 ± 165 mmHg%, p = 0.974; cGWE 89 ± 5 vs 87 ± 5%, p = 0.177). A significant inverse correlation was found between baseline cGWI and left atrial volume index (r=-0.5, p = 0.03). Conclusions patients with severe aortic stenosis and preserved LVEF show a good LV performance before and after TAVI, with a significant decrease in MW indices after TAVI, because of the reduced afterload due to AS treatment. The negative correlation between left atrial volume and cGWI may reflect the extent of myocardial damage in AS. However, further studies with larger sample size and appropriate follow-up are needed to evaluate the role of MW in prognosis and risk stratification of this subset of patients.

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3–10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8–11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3–15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

Background Adults with congenital heart disease (ACHD) are frequently affected by thyroid diseases (TD). However, the clinical relevance of TD in ACHD remains unknown. Purpose We aimed to describe the prevalence of TD in the ACHD population and to ascertain whether TD are associated with worse outcome. Methods Clinical data on all consecutive patients aged >18 years attending our ACHD unit for a day-case between 2014 and 2019 were retrospectively collected. For statistical analysis, a composite endpoint was created combining the following events at follow-up: hospitalization for heart failure, new-onset tachyarrhythmic or bradyarrhythmic events and death. Results Four hundred ninety-five ACHD patients with a median age of 32.2 [24.5–45.6] years (46% male) were included. There was an overall prevalence of patients with moderate or complex lesions (414=84%). Compared to the group with no history of TD, patients in the TD were older, (41.9 [29.7–53.5] vs 30.2 [24.3–39] years; p Median follow-up was 9.4 [4.5–13.1] years. Patients with TD had a higher unadjusted mortality rate, with a trend towards statistical significance (p=0.07). Sixty-four (42%) patients in the TD group and 43 (12.5%) met our composite endpoint, leading to a 10-year survival free from events of 53.7% Vs 86.5%, respectively (p Conclusion TD is a strong predictor of adverse outcome in the ACHD population after exclusion of potential confounding factors, being related to a fourfold increased risk of events at follow-up. Funding Acknowledgement Type of funding sources: None. Figure 1Table 1

Objective. To study the correlations between corneal distortion and morphological features in different kinds of eyes such as healthy ones (HE), ones previously undergone myopic PRK (PRKE), ones affected by keratoconus (KCE) and keratoconus eyes previously undergone corneal collagen crosslinking (CCCE). Materials and Methods. In this retrospective comparative study, a total of 106 HE of 106 patients, 58 PRKE of 58 patients, 33 KCE of 33 patients, 28 CCCE of 28 patients were included. A complete examination of all eyes was followed by tomographic (Pentacam, Oculus, Wetzlar, Germany) and biomechanical (Corvis ST, Oculus, Wetzlar, Germany) evaluation. Differences among Corvis ST (CST) parameters in the different groups have been analyzed. Linear regressions between central corneal thickness (CCT), intraocular pressure (IOP) and anterior corneal curvature measured with Simulated Keratometry (SK), versus corneal deformation parameters measured with Corvis ST in the different groups, have been run using SPSS software version 18.0. Results, HE showed a significant correlation between main curvature power of the cornea within the central 3 mm expressed in Diopters (KM) and 6 CST parameters; between CCT and 4 CST parameters and between IOP and 5 CST parameters. PRKE showed a significant correlation between KM and 3 CST parameters; between IOP and 4 CST parameters and none between CCT and CST parameters. KCE showed a significant correlation between SK and 3 CST parameters; between IOP and 3 CST parameters and none between CCT and CST parameters. CCCE showed a significant correlation between KM and 5 CST parameters; between CCT and 1 CST parameters and between IOP and 5 CST parameters. Discussion. Data of this study suggest that both corneal curvature and IOP could have a greater influence on the corneal deformation, compared to central corneal thickness (CCT). These results should be taken into account by further studies aiming to assess biomechanical corneal characteristics.

Patient presentation During a routine check up, a 47yo man with Tetralogy of Fallot and congenital absence of left pulmonary branch was found to have a vegetation on his prosthetic pulmonary valve. His surgical history included TOF repair with left pulmonary branch bypass aged 4 years and a redo surgery for pulmonary valve replacement 3 years earlier. Before last surgery, CMR showed severe pulmonary regurgitation, dilated RV with mildly impaired systolic function (EF 40%) and absent flow in left pulmonary branch due to bypass occlusion. Diagnostic work-up The patient reported increasing shortness of breath (NYHA class III) over the last months. He reported one single fever peak two months before.He was on Apixaban and Amiodarone for previous history of AF. He was afebrile and an ejective systolic 4/6 murmur was heard. He was in sinus rhythm at 70 bpm. The TTE showed dilated RV with severely reduced systolic function (FAC 12%), severe pulmonary stenosis (peak gradient of 70 mmHg) with mild regurgitation, and a mobile and echogenic vegetation of 10 X 9 mm was seen on the prosthetic pulmonary valve. His blood tests at the admission demostrated raised WBC (9.460/uL) and PCR 11.7 mg/dl (n.v. < 3.0). The PCR remained stable during the following days. Serial blood samples for cultures were obtained, but all resulted negative. Uncommom causes of negative blood culteres infective endocarditis were investigated with specific serological tests for research of fastious agents, but all resulted negative. Antinuclear and antiphospholipid antibodies were also tested. A total-body CT was performed and it showed several liver formations. A FDG PET-CT was requested and it demostrated active marked glucose uptake by a mediastinic node, as well as by liver, brain and prosthetic pulmonary valve. Diagnosis and outcome After a careful review of all the clinical and imaging data, our opinion was that the most probable diagnosis was non infective thrombotic endocarditis in patient with metastatic cancer. In this situation, the valvular glucose uptake was likely due active thrombus formation rathen then being a sign of inflammatory response. Unfortunately, the patient died suddenly two weeks after the PET-CT and it was impossible to confirm the diagnosis with biopsy. Conclusion Differential diagnosis of cardiac vegetations is a challenging process including microbological tests, multi modality imaging and clinical reasoning. It is always necessary to consider alternative diagnosis, even when traditional imaging tests seem to suggest infective endocarditis. Non infective thrombotic endocarditis are a rare form of negative blood culteres endocarditis related to systemic hypercoagulable state (i.e. antiphospholipid syndrome, systemic lupus, behcet syndrome, cancer). Malignancies can be considered an unusual cause of cardiac vegetation and they must be taken into account on differential diagnosis. Abstract 1107 Figure. FDG uptake in pulmonary position

Background Rupture of Sinus of Valsalva (rSOV) is a rare and potentially life-threatening condition often misdiagnosed. Percutaneous device closure has been replacing surgical repair as a treatment of choice. However, long-term outcome is poorly documented. Methods Echo database (2001-2019) was searched for patients >16y with rSOV. Clinical data were collected from ACHD database. Marfan Syndrome patients were excluded. Results Fifteen patients (42.2y, 10M) were diagnosed with rSOVbetween 1979 and 2019. HF symptoms at initial presentation were reported in 50%. All cases were diagnosed by TTE with finding of high velocity continuous flow from SOV to right heart. Two were initially misdiagnosed as VSD. Digital imaging recordings of 10/15 were available. The aortic root was dilated in 8/10. Four had asymmetrical SOV dilatation. LV and LA were dilated in 7/10 and 9/10. Significant aortic regurgitation was in 4. Two had RVOTO. RVSP was always raised. Echo findings are summarised in the Table. Mean FU after repair was 10,7y (0,9-39). Ten patients had surgical repair and 5 device closure. Seven had repair of concomitant lesions (4 VSD closure and 3 AVR) at the time of the procedure. One redo device closure was performed. During FU 1 died from Cardiomyopathy. At the latest FU significant improvement in functional class, LV and LA size and RVSP was found. Conclusion Patients with rSOV may present with acute HF. High velocity continuous flow from SOV to right heart on TTE is characteristic feature for diagnosis. Percutaneous closure is an attractive alternative to surgery in patients with isolated lesion. Significant haemodynamic improvement can be achieved with good long-term haemodynamic results Tot = 15 Initial findings Latest FU NYHA class 4 class I 2 class II 2 class III 4 class IV 3 unknown 11 class I 2 class II 1 class III 0 class IV* SOV (mm) 38.2 (33-44) STJ (mm) 36.2 (26-42 Asc Ao (mm) 30.3 (25-34) rupture site 8 RC sinus, 2 NC sinus Shunt to 8 RVOT, 1 RA, 1 RVOT + RA LVEDV (ml) 169.7 (114-330) 120 (67-230)* LVESV (ml) 66(42-130) 46 (28-80)* LAVi (ml/m2) 53.1 (30-129) 35 (24-53)* LV EF% 61.2 (57-65) 60.4 (50-70) RVSP (mmHg) 53.2 (37-130) 24.06 (15-32)** Pre VS post procedure p-value: * P Abstract P1598 Figure. PLAX in patient with ruptured RC sinus

Background Immune checkpoint inhibitors (ICIs) are a novel class of antineoplastic drugs which have dramatically changed the management of non-small cell lung cancer. ICI-associated cardiotoxicity is rare, but potentially fatal, presenting in most of cases as autoimmune acute myocarditis during the first phase of treatment. However, since an extensive cardiac monitoring is not routinely performed in most immunotherapy trials, the true incidence of ICIs related cardiac effects is largely unknown. Aim Aim of our study is to ascertain a possible subclinical cardiac involvement in patients with non-small cell lung cancer treated with ICIs. Methods We prospectively recruited 40 patients (13 males; mean age 64.3 ± 8.3 years) starting immunotherapy with PD-1/PDL-1 inhibitors for non-small lung cancer between January and August 2018. Demographic and clinical data were recorded and all patients underwent a standard 12-lead ECG and a transthoracic echocardiogram with assessment of left ventricular global longitudinal strain (LV GLS). Furthermore, blood samples for pro BNP-nt and high sensitivity Troponin T (hsTnT) measurements were collected. Serial assessments were performed before and 1 and 3 months after initiation of immunotherapy. Results A history of previous coronary artery disease was documented in eight cases (20%). At follow-up no cardiovascular events were recorded. Compared with baseline, echocardiographic parameters of ventricular function did not significantly changed at 1 and 3 months (LVEF 61 ± 6% at baseline, 61 ± 5% at 1 month, 60,2 ± 5% at 3 months, p =0.1; E/E’at baseline 9.2 ± 3, 9.2 ± 2.8 at 1 month, 9.1 ±3,5 at 3 months, p = 0.2;TAPSE 20 ± 3.4 mm at baseline, 21.3 ± 2.8 mm at 1 month, 20 ± 3.8 mm at 3 months, p =0.1; LV GLS -20.3 ± 3.6% at baseline, -20.8 ± 2.3% at 1 month, -20.6 ± 3% at 3 months; p = 0.4). Analogously, no significant increase in circulating levels of cardiac biomarkers was found with hsTnT Conclusions In our study no significant clinical or subclinical evidence of myocardial involvement was detected during treatment with ICIs in patients with non-small cell lung cancer, thus suggesting the potential cardiovascular safety of this promising class of antineoplastic drugs.

Analyses carried out on pear varieties Conference, Comice and William and sixty-eight apricot varieties, grafted in open field on different rootstocks, showed their susceptibility to 'Candidatus Phytoplasma pyri', transmitted by Cacopsylla pyri, and to 'Candidatus Phytoplasma prunorum' infection, caused by Empoasca decedens, respectively. In order to find a source of immunity to ‘Ca. P. pyri’ and to ‘Ca. P. prunorum’ new different variety/rootstock combinations of pear and apricot were tested in the period 2002-2008. All the plants, cultivated in pot and covered by anti-aphid tissue under greenhouse conditions, were patch-grafted by infected tissues containing the specific phytoplasmas. The plants belong to seven variety/rootstock combinations for pear and seven combinations for apricot. Young healthy potted plants belonging to the pear combination Comice/P. communis and to the apricot combination Palummella/Myrobolan, both susceptible in open field to the associated phytoplasmas transmitted by the specific vectors, were also used and patch-grafted. Molecular analyses carried out by PCR/RFLP analyses on leaf samples to detect the presence of the pathogens showed that the only susceptible combination was William/Pyrus betulaefolia. Neither the pear combination Comice/P. communis nor the apricot Palummella/Myrobalan 29 C, susceptible to phytoplasmas in open field, become infected after patch-grafting under greenhouse. Thus the results showed that patch-grafting cannot be utilized in young potted plants for artificial transmission of these two phytoplasmas.

The nudibranch Discodoris indecora shows a perfect camouflage on its prey, the dictyoceratid sponge Ircinia variabilis. Shape and colour of the nudibranch are remarkably similar to that of the sponge which is widespread in the shallow waters of the Mediterranean Sea. The metabolite pattern of /. variabilis is dominated by unusual molecules, the sesterterpenoids palinurin and variabilin, containing 25 carbons and displaying at the ends a ^-substituted furan ring and a tetronic acid. However, a chemical polymorphism has been recently described for /. variabilis. Some specimens contain either palinurin or variabilin whereas others possess a mixture of both sestertepenoids. During the study of Mediterranean sponges, a linear sesterterpenoid related to palinurin and variabilin was found in Ircinia fasciculata, that from a taxonomic point of view is closely relatedto Ircinia variabilis. Discodoris indecora shows a typical defence behaviour when it is disturbed, secreting a copious white slime that contains large amounts of palinurin and variabilin. Most likely the animal is able to transfer the sponge metabolites from the digestive glands to mantle glands. Electron micrographs of the nudibranch mantle showed the presence of unicellular glands characterized by a cylindrical vacuole with a big nucleus on the basis. The glands were concentrated in the most conspicuous tubercles of the dorsal mantle. Probably, the sponge metabolites are stored in these glands. Comparative chemical analysis of mucous secretions, dorsal tubercles, mantle, foot, digestive glands and hepatopancreas of D. indecora confirmed this hypothesis. Palinurin and fasciculation were, of course, present in the digestive glands but they were also found in the mucus and in the mantle sections enriched by the above described unicellular glands. The defensive role of palinurin and variabilin, strongly suggested by their anatomical location, was

We propose a sharpness enhancement technique for video and decoded image sequences. Basically, the enhancement is accomplished by adding overshoot to luminance edges in an unsharp masking-like way. However, the optimal amount of overshoot added for a high image quality depends on the local image statistics. For this purpose, controls are introduced, to improve the performances and to adapt the operator to moving sequences with different characteristics. Both spatial and temporal information is used to enhance details, avoiding blocking artifacts and noise.

A total of 1095 patients with operable breast cancer and en-rolled in a randomized clinical trial were analysed for estrogen (ER) and progesterone (PgR) receptor content of their primary tumor, and the relationships between steroid receptor status and several epidemiologic characteristics were studied. The proportion of ER+ and median ER levels increased with age: compared to women younger than 40, those aged 66 or more were approximately three times more likely to have an ER+ tumor (OR = 3.0, 95% C.I. = 1.6–5.7). This difference tended to be more marked after comparison between patients with ER > 100 fmol/mg protein and ER- within the same age groups: OR = 7.04, 95 % C.I. = 2.89–17.12. No association emerged between age and PgR. ER status and concentrations were independent of menopausal status after adjustment for age, whereas the proportion of PgR+ and PgR levels were significantly lower in postmenopausal patients of the same age. The distribution of ER and PgR profiles was similar in relation to family history of breast cancer, reproductive events and other selected epidemiologic characteristics of the patients.

In this paper, we present an unsharp masking-based approach for edge enhancing for TV application. The proposed scheme enhances the true details, limits the overshoot near sharp edges and attenuates the temporal artifacts which are visible in an image sequence. Simulations show that the processed sequence presents sharp edges which make it more pleasant to the human eye. Moreover, the amount of noise and nonhomogeneities in the sequence are clearly reduced.

The occurrence of an angiosarcoma of the residual breast after conservative surgery and adjuvant radiotherapy for early mammary carcinoma is a very rare event. In western countries only 57 cases have been published in the literature (5 in Italy) since the first described case in 1987. Radiotherapy seems to be the most important etiological factor in the development of the neoplasm. Diagnosis is often delayed, owing to the "benign" aspect of the lesion. The only effective treatment is residual mastectomy, because chemotherapy is ineffective. The prognosis is often dismal, because of the aggressive behaviour of the lesion in most cases. The case of a patient with a multicentric secondary angiosarcoma of the breast recently operated on is described.

Assessment of presence of metastatic disease (m.d.) in bladder cancer (b.c.) can represent a main problem as influencing the appropriate therapeutic policy (mostly the indication to radical surgery). Evaluation of the real cost-effectiveness ratio of radiographic and radionuclide diagnostic work-up induced us to retrospectively review historical data about our b.c. patients (pts). From March 1988 to June 1991, 76 not consecutive pts with histologically proven bladder cancer were included in this study. 5 Pts were staged as T1, 25 as T2, 18 as T3a, 23 as T3b, 5 as T4. 2 Pts were graded as G1, 27 as G2, 44 as G3, 3 as Gx. Age varied from 39 to 89 years (average: 62.3). 79 Pts underwent the "basic work-up" (including chest plain film, bone and liver scans) and at least one follow-up control. 266 chest plain films, 22 chest x-ray tomograms, 2 chest CT scans, 27 bone x-ray tomograms, 231 bone scans, 240 liver scans, 17 liver ultrasonographies were totally realized. All pts underwent at least an abdomen-pelvic CT, but related results are not considered in the study. Fine needle aspiration cytologic biopsies were realized in selected cases; also these results are not selectively reported here. Together with cytologic positive results, only progression of m.d. was considered as its definite presence. Conventional x-ray examination (plain film integrated by x-ray tomograms of "suspicious" findings) resulted sufficiently complete and accurate to reveal chest m.d. Concerning skeletal diagnostic survey, only 6 pts (26%) out of 23 pts with "positive" bone scans really resulted affected by m.d.(ABSTRACT TRUNCATED AT 250 WORDS)

The Autors have examinated endocrine function in girls during puberal age. Have been showed datums relative to cultures effected on vaginal secrets withdrawn from little girls in prepuberal age. They have also studied polimicrobic vaginal flora related to sexual hormone levels. Have been controllated correlations between vaginal microbic status and cytohormonal response at different hormonal situation. The Doderlein presence is as much greater so higher is the oestrogen and progesterone (E/P) ratio, while the Doderlein bacillus isn't present when E/P ratio is lower. Perhaps in puberal age other factors than oestrogen and progesterone levels, could influence vaginal polymicrobic flora.

A survey of glove perforation in 200 consecutive Caesarean sections (100 elective and 100 emergency) was undertaken. A total of 1276 gloves were tested for punctures after the end of the operation. Evidence of perforation of one or more gloves was found following 39 elective (234 gloves, 37.2%) and 43 emergency sections (290 gloves, 44.8%) (total 82, 41%). Only in 17 of these cases (20.7%) was it realised that a perforation had actually occurred. The surgeons were found to be significantly more at risk of perforation than the other members of the operating team.

We made a study on patients suffering from neoplasias treated with cisplatinum to compare antiemetic efficacy of alizapride or associated to dexamethasone. We divided patients in two groups. We somministred alizapride alone to the first group and alizapride plus dexamethasone to the second one. We evaluated presence or absence of emesis, its intensity and eventual tossic effects due to the drugs through an autocompilative questionnaire given to the patients. Our results didn't show important statistical differences between the two groups, though association with dexamethasone gets better emesis control. Alizapride anyway, didn't present important collateral effects, particularly extrapyramidal ones.

770 Background: Epirubicin and Vinorelbine alone or in combination are considered active in ABC.The optimal duration of a chemotherapic treatment in ABC patients is not know. Otherwise Epirubicin h...