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Aims In breast cancer (BC) patients treated with anthracyclines-based therapies, we aim at assessing whether adjuvant drugs impact cardiac function differently and whether their cardiotoxicity has a regional pattern. Methods and results In a multicentre study, 146 BC patients (56 ± 11 years) were prospectively enrolled and divided into three groups according to the received treatments: AC/EC-Group (doxorubicin or epirubicin + cyclophosphamide), AC/EC/Tax-Group (AC/EC + taxanes), FEC/Tax-Group (fluorouracil + EC + taxanes). Fifty-six patients of the total cohort also received trastuzumab. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were calculated before starting chemotherapy (T0), at 3 months (T3), at 6 (T6), and 12 months (T12). A ≥10% drop of EF, while remaining within the normal range, was reached at T6 in 25.3% of patients from the whole cohort with an early decrease only in FEC/Tax-Group (P = 0.04). A ≥15% GLS reduction was observed in many more (61.6%) patients. GLS decreased early both in the whole population (P Conclusions The decrease of GLS is more precocious and pronounced in BC patients who received FEC + taxanes. Cardiac function further worsens after 6 months of adjuvant trastuzumab. All LV segments are damaged, with the anterior septum and the apex showing the greatest impairments.

Background The new methodological standard in stress echo (SE) is the comprehensive approach with ABCDE protocol: step A for regional wall motion abnormalities (RWMA); step B for B-lines by lung ultrasound; step C for left ventricular contractile reserve (LVCR); step D for Doppler-based coronary flow velocity reserve (CFVR) in left anterior descending coronary artery; and step E for imaging-independent EKG-based heart rate reserve (HRR). Purpose To assess the feasibility of ABCDE-SE in a prospective, large scale, multicenter, international, effectiveness study. Methods From September 2016 to December 2019, we enrolled 4,585 all-comers patients (age 63±11 years, 2,566 males, 56%; ejection fraction 61±9%) with known or suspected chronic coronary artery disease referred to clinically-driven SE with exercise (n=1,774, 38.7%), dipyridamole (n=2,403, 52.4%), dobutamine (n=375, 8.2%) or adenosine (n=33, 0.7%). Recruitment involved 13-certified laboratories of 7 countries. All patients underwent ABCDE-SE. The same transducer was used for cardiac and lung scan. Criteria for abnormal response were: stress-induced changes in RWMA in 2 contiguous segments for step A; stress-rest increase in B-lines ≥2 for step B (4-site simplified scan, each site scored from 0= A-lines or black lung to 10= white lung for coalescing B-lines); LVCR ≤2.0 for exercise and dobutamine (≤1.1 for vasodilators) for step C; CFVR in LAD ≤2.0 for step D; HRR (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators) for step E. Results Success rate was 98%, 100%, 99%, 86% and 100% for A, B, C, D and E steps, respectively. The positivity rate was 19% for A, 27% for B, 35% for C, 27% for D and 37% for E. All 5 parameters were normal in 1,496 patients (32.6%), all 5 were abnormal in 183 patients (4.0%). Most patients had abnormal response of 1 (n=1,356, 29.6%), 2 (n=788, 17.2%), 3 (n=477, 9.7%) or 4 (n=315, 6.9%) criteria (see Figure). Conclusions ABCDE-SE is extremely feasible, user-friendly, with minimal increase in imaging and off-line analysis time. It allows a comprehensive and personalized functional stratification assessing different vulnerabilities: epicardial coronary artery stenosis (step A), pulmonary congestion (step B), global myocardial dysfunction (step C), coronary microcirculatory dysfunction (step D), and cardiac autonomic nervous system imbalance (step E). The SE response is not only black and white with step A but can be effectively titrated from benign green code (all steps negative) to more functionally malignant red code (at least 3 steps positive). Figure 1 Funding Acknowledgement Type of funding source: None

Background Bicuspid aortic valve (BAV) is the most common congenital heart disease, affecting 0.5%–2% of the general population. It is associated with valvular dysfunction (aortic stenosis and/or regurgitation, endocarditis) but also with a wide spectrum of aortopathy with unpredictable clinical presentations. The role of the raphe is still controversial. Methods The REgistro della Valvola Aortica Bicuspide della Società Italiana di ECocardiografia e CArdiovascular Imaging is a retrospective/prospective, multicenter, observational registry, with definitive diagnosis of BAV. Anamnestic, demographic, clinical, and instrumental data are collected into dedicated software at first evaluation and during follow-up. Aortopathy was defined as: annulus ≥14 mm/m2; root ≥20 mm/m2; sino-tubular junction (STJ) ≥16 mm/m2; ascending aorta (AA) ≥17 mm/m2; it was classified in: type A, dilation of the ascending aorta; type B, dilation of the aortic root and the ascending aorta; and type C, isolated dilation of the aortic root. Patients were divided in two groups; those with raphe and those without. Results At December 2019, 800 patients with BAV (Male, 73.3%; M:F ratio 2.9; Mean Age at diagnosis 44±23 years) have been included in the registry. Prevalence of hypertension was 29%, diabetes mellitus 3%, smoking-habit 8%. We reported a majority (42.7%, 342) of patients with type 1, followed by type 2 (10.2%, 82) and type 3 (3.7%, 30). No gender differences were observed according to BAV phenotypes, while male gender was associated to higher prevalence of aortic valve regurgitation (p=0.0003). Moreover, in patients with raphe, aortic stenosis (49.8% vs 38.4%; p=0.014) and aortopathy (57.4% vs 46.1%; p=0.034) were significantly prevalent (see Table 1). Of note no difference about aortic regurgitation (62.8% vs 48.7%; p=0.064) between two groups were detected. At univariable logistic regression analysis the presence of raphe was significantly associated with aortopathy [OR: 1.57; 95% CI: 1.02–1.42; p=0.037] especially with Type B Aortopathy [OR: 0.55: 95% CI: 0.33–0.93: p=0.02]. Conclusion Preliminary data from Italian Multicenter REBECCA registry highlight that, in patients with BAV, the raphe is not an innocent bystander but a risk factor for aortic stenosis and type B aortopathy. Funding Acknowledgement Type of funding source: None

Myocardial dysfunction are the most concerning cardiovascular complications of cancer therapies with a poor prognosis, so it’s critical to detect subclinical cardiac abnormalities in order to start cardioprotective therapy early or increased surveillance frequency. Global longitudinal strain (GLS) by echocardiography is an excellent tool for assessing regional and global left ventricular (LV) function. Mechanical dispersion (MD) reflects heterogeneous myocardial contraction, evaluated in many cardiopathies. We evaluated subclinical myocardial dysfunction by GLS and MD using 2D Speckle-tracking Echo, in order to established if MD could be a predictor of ventricular dysfunction in the field of Cardiotoxicity (CTX). Were enrolled 42 women with breast cancer chemotherapy-treated and underwent to Echo evaluation during 3- and 6-months follow-up, compared to evaluation performed before starting chemotherapy (T0). Depending on chemotherapy type were identified 2 groups: Anthracyclines ± Taxol treated (group 1) and Anti-HER2 treated (group 2). CTX diagnosis was made according ESC criteria: LVEF 10% or GLS decrease >15% compared to previous check. At three months, 28% patients (p We believe that MD is a predictor of ventricular dysfunction earlier than GLS during Anti-HER2 treatment, so in this field MD could integrates information obtained from GLS about subclinical dysfunction.

Anderson-Fabry disease (AFD) is a rare X-linked metabolic disorder due to deficiency in lysosomal enzyme activity of a-galactosidase A, resulting in pathological accumulation of glycosphingolipids in several tissues and a progressive multi-organ dysfunction. The Global Longitudinal Strain (GLS) of the left ventricle (LV) by Speckle-tracking echocardiography (STE) has been show to detect subclinical cardiac involvement in many cardiomyopathies. The Mechanical Dispersion (MD), derived from STE is considered able to reflect a heterogeneous myocardial contraction, evaluated in many cardiopathies. A reduction in GLS was associated with myocardial fibrosis in the subclinical stages of AFD cardiomyopathy, but there is no MD data in AFD. The aim of the study was to evaluate the distribution of GLS and MD of LV in patients with AFD. 47 consecutive AFD adult patients treated (37F, 12 M, age 45 + 17 years) were examined by a complete echocardiographic examination from a Vivid E95 ultrasound scanner (Horten, Norway). The STE post-processing was performed by Echopac 2.02, in apical long-axis, 4-chambers, and 2-chambers views to determine GLS and MD. Data were expressed as mean± standard deviation. The comparison between the AFD group and 20 normal subjects (N) was performed with unpaired T-test. Compared to N, the AFD group showed higher values of LVMi, LAVi, E/E’, and MD, but a lower value of GLS (Table). GLS was significantly lower in the basal (sept p In patients with AFD, MD added to GLS seems to be a promising tool for the early diagnosis of segmental dysfunction . Table1: Results AFD N p< m SD m SD LVMi g/sqm 77.1 29.8 62.3 14.1 0.008 LVEF % 65.7 5 63.6 3.5 0.04 LAVi ml/sqm 25.5 11 18.2 4.5 0.000 E/E" 8.3 3 5.4 1.1 0.000 TV vmax m/s 2.2 0.4 2.1 0.3 - LV GLS % -17 4 -20 2 0.003 LV MD ms 52 38 29 8 0.000

Aims To assess the incremental value of real-time three-dimensional echocardiography (RT-3DTE) over contrast transthoracic echocardiography (TTE), compared with contrast transesophageal echocardiography (TEE) in the identification of patent foramen ovale (PFO). Methods and results Eighty-one consecutive patients with history of migraine headache (MH) or unexplained cerebrovascular events (CE) were examined using RT-3DTE, contrast TTE, and contrast TEE in sequence. Feasibility of RT-3DE in patients with MH and CE was 98 and 91%, respectively. Mean time for 3D colour data set acquisition was 9 ± 5 min. PFO was diagnosed using contrast TEE in 36 patients (overall prevalence = 44%). Diagnostic accuracy of RT-3DE was significantly higher than that of contrast TTE: sensitivity 83 vs. 44%, P < 0.001; specificity 100 vs. 100%, P 7 = NS; positive predictive value 100 vs. 100%, P = NS; negative predictive value 88 vs. 69%, P < 0.01; accuracy 93 vs. 75%, P < 0.003. Five of the six patients in whom RT-3DTE did not identify PFOs showed a defect diameter smaller than 2 mm. Conclusion RT-3DTE is a feasible, accurate, and reproducible technique to detect PFO without the need of saline contrast injection. Its accuracy is superior to contrast 2D TTE and close to that of contrast TEE.