Abstract Background Granular sparkling is a well-known echocardiographic feature found in patients with transthyretin-related cardiac amyloidosis (ATTR-CA). However, there is no objective technique for quantifying this feature, which therefore remains a qualitative, elusive and ultimately unreliable imaging characteristic. Recent evidence suggests that radiomics and, in particular, ultrasonomics could play an important role in the non-invasive tissue characterization of cardiomyopathies through the study of specific myocardial texture features. Purpose The aim of this study is to statistically and geometrically characterize granular sparkling as a volume-independent texture property of the myocardium in patients with ATTR-CA. Methods We retrospectively collected echocardiogram video-clips in parasternal long axis (PLAX) and 4-chamber (4CH) views of 229 patients with ATTR-CA, and 224 age- and gender-matched hypertensive patients without any known cardiac disease. From each video-clip, one end-diastole frame was extracted and annotated by an expert to identify a region-of-interest (ROI) within the interventricular septum. Left ventricle chamber masks were also extracted, and used as a brightness reference to enforce invariance w.r.t. the settings of the specific ultrasound system (Fig. 1). Because many established radiomic textural features are heavily volume-confounded, we analyzed the ROI texture by extracting a subset of volume-invariant radiomic features (i.e. ROI-independent), as well as morphological granulometry features. We then fitted a logistic regression classifier to discriminate between ATTR-CA and controls based on the computed textural features. Results 94 radiomic features were identified, of which 73 were volume-invariant. The texture-based classifier predicted the diagnosis with a cross-validated accuracy of 91%, a specificity of 90% and a sensitivity of 92% by utilizing 73 volume-invariant radiomic features on both PLAX and 4CH views (Fig. 2). The addition of granulometry and the further addition of 11 volume-confounded features and 9 shape features to the model did not significantly enhance its discriminative performance (Fig. 2). The top 10 volume-invariant discriminative features were largely consistent in PLAX and 4CH views (Fig. 2), with variables descriptive of greater heterogeneity (such as glszm_ZoneEntropy and glszm_RunEnNtropy) and a higher spatial rate of change (such as ngtdm_Complexity) in the texture of ATTR-CA frames as compared to control frames. Conclusions Our results confirm the ability of radiomics in detecting subtle differences in the myocardial texture of echocardiographic images between patients with ATTR-CA and hypertensive controls. High levels of accuracy are obtained with a purely texture-based, volume-independent set of features. These findings suggest that the diagnosis of ATTR-CA could be simplified and made earlier using a statistical model based on the extraction of radiomic features.Figure 1Figure 2

Abstract Introduction The use of left ventricular assist devices (LVAD) is increasing both as bridge-to-transplantation or destination therapy, considering the lack of heart donors for transplantation in advanced heart failure (AHF) population. Right ventricular post-implantation failure, major bleedings and infective events remain the principal adverse events in LVAD carriers, thus an accurate selection of candidates is needed. Purpose To identify between clinical, laboratory, standard and advanced (Speckle Tracking, STE) echocardiography, and right heart catheterization (RHC) indices, the best predictors of outcome after LVAD implantation. Materials and Methods We screened in our third-level center 30 patients with AHF, followed up from May 2013 to February 2022, for the assessment of LVAD implantation suitability. They all underwent a complete cardiological history collection, electrocardiography, standard and STE left ventricular (LV) and left atrial (LA) size and function assessment. Regarding the right ventricle, SIENA score parameters, including RV sphericity index, RV free wall longitudinal strain (LS), right ventricular fractional area change (RVFAC), and 3D ejection fraction were used for exclude RV disfunction. RHC was performed on the same day of echocardiography. Follow-up was conducted at 1, 3, 6, 9 and 12 months repeating all the assessments, for the occurrence of RV failure, all-causes mortality, hemorrhagic events and re-hospitalization for heart failure. With a univariate and multivariate statistical analysis, we went to test among all the parameters the possible predictors of outcome. Results The final population consists of 29 patients (93% male, mean age of 63±11 years), in NYHA class III or IV and a severe reduction of left ventricular (LV) ejection fraction (EF), in whom arterial hypertension and smoking, present or previous, were present in 58% and 65% of cases, respectively. The population was divided into two groups according to the occurrence of at least one cardiovascular event. 11 major events were recorded: including 4 hemorrhagic events, 3 all-causes mortality and 4 hospital admission for HF. No RV failure occurred in the first 12 months of follow-up. No differences were identified between the two groups in terms of echocardiographic indices and RV function, including RVFAC or RV-FWLS. At univariate analysis (see Table 1), the only parameter able to predict major CV events was central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio, obtained by RHC, an index of balance between right and left heart filling pressure. Conclusions A careful application of SIENA score indices before LVAD implantation can significantly reduce the incidence of post-operative RV failure, as in our small population. Our results also confirmed the paramount role of RHC in the diagnostic work up of AHF.

Aims:Myocardial work (MW) is a relatively novel non-invasive echocardiographic method with increasing fields of application. Normal reference ranges of MW indices in patients who have undergone a heart transplant (HTx) have not been determined yet. The aim of this study was to obtain the reference ranges for 2D echocardiographic indices of MW for adult HTx patients and to compare them with the results of the European Association of Cardiovascular Imaging (EACVI) Normal Reference Ranges for Echocardiography (NORRE) study. Methods and results:All consecutive HTx patients admitted at our institution (University Hospital of Siena, Italy) between September 2019 and May 2022 who underwent endomyocardial biopsy (EMB) were considered. Patients with a history of rejection, a history of coronary artery vasculopathy, either acute cellular rejection or acute antibody-mediated rejection at EMB, and donor-specific antibodies were excluded. MW retrospectively performed for the included patients was retrieved, and the results were compared with those from the EACVI NORRE study. Out of 176 HTx patients who underwent EMB, 94 patients were excluded. The study population consisted of 82 HTx patients [68.3% male, median age 53 (46-62) years]. The median duration from HTx was 5 (2-22) months. The main MW indices such as global work efficiency (GWE, 84 ± 8%), global work index (GWI, 1447 ± 409 mmHg%), global constructive work (GCW, 2067 ± 423 mmHg%), and global wasted work [GWW, 310 (217-499) mmHg%] did not differ according to gender. Each of these indices significantly differed from those reported in the EACVI NORRE study (P-value <0.001), with lower GWI, GCW, and GWE and higher GWW values in the HTx population. Conclusion:This study provides reference ranges for MW indices in an adult HTx population free from transplant-related complications which proved to be different from those previously reported in healthy volunteers.

Aims:Speckle tracking echocardiography increasingly supports left atrial (LA) strain (LAS) analysis for diagnosis and prognosis of various clinical conditions. Prior limitations, such as the absence of dedicated software, have been overcome by validated ventricular-based software. A newly automated real-time and offline LA-specific software have now become available on echocardiographs and dedicated workstations. This study aimed at comparing LA strain measures obtained from new fully automated software vs. traditional semi-automated ventricular-based methods in different groups of patients. Methods and results:Two operators acquired LA images in a mixed population of healthy individuals and patients with pressure overload (hypertension and aortic stenosis) or pressure-volume overload (mitral regurgitation and heart failure). Subjects with prosthetic valves, heart transplant, or atrial fibrillation were excluded. Strain analysis was performed twice by old semi-automated software and new LA dedicated. LAS was then measured online on the scanning echocardiograph. Overall, 100 patients were analysed (41 healthy subjects, 28 pressure overload, 31 volume overload). LAS proved to be highly reproducible with both software. The dedicated method exhibited slightly superior inter- and intra-operator reproducibility. The online software results showed a nearly perfect reproducibility with offline software [intraclass correlation coefficient = 0.99 [0.99; 1.00]] in addition to being able to save an average of ∼30 s. Conclusion:The recently developed fully automated software for dedicated LAS analysis demonstrates excellent inter- and intra-operator reproducibility, making it a reliable and efficient strain calculation method in routine clinical practice. Another advantage of online LAS calculation is time efficiency.

Abstract Background Recent advances in imaging and increased disease awareness have led to a significant rise in newly diagnosed cases of cardiac amyloidosis (CA) over the past decade. However, there remains a lack of epidemiological data regarding the true incidence of the disease. Purpose To determine the incidence and clinical characteristics of newly diagnosed cases of CA in a large Italian population. Methods Subjects with suspected CA underwent diagnostic work-up in 20 Centers in Tuscany and Umbria regions within the Cardiac Amyloidosis RegistRY (CARRY), between January 1st 2022 and December 31st 2022. Results A total of 551 subjects were enrolled in the registry, with complete data on the final diagnosis available for 448 individuals. CA was diagnosed in 179 patients (40%), with 28 (16%) classified as light chain CA (AL-CA), 114 (64%) wild-type transthyretin CA (ATTR-CA), 12 (7%) variant ATTR-CA, and 25 (13%) undetermined CA. Considering a reference population in Tuscany and Umbria in 2022 (4,518,388, according to the Italian National Institute of Statistics), this yields an estimated cumulative incidence of 39.6 cases per million inhabitants per year. Alternative diagnoses in the remaining patients mostly included hypertensive heart disease (n=157, 58%), hypertrophic cardiomyopathy (n=25, 9%), moderate-to-severe valvular heart disease (n=11, 4%), or a mixed phenotype (n=72, 27%). The primary referral pathway for the suspicion of CA was cardiological (n=345, 77%), followed by incidental finding during screening visits (n=58, 13%), and haematology referral (n=33, 7%). Patients with confirmed CA were older (81 [75-85] vs. 77 [72-83] years, p<0.001), and more frequently reported musculoskeletal red flags of CA, such as carpal tunnel syndrome (85 [48%] vs. 53 [20%] years, p<0.001), and spontaneous tendon rupture (39 [22%] vs. 18 [7%] years, p<0.001). Median time to diagnosis from clinical suspicion was 73 (37-140) days for CA and 84 (36-156) days for alternative diagnoses (p=0.564). Conclusions The diagnosis of CA is on the rise globally, with an estimated incidence of 39.6 new cases per million inhabitants per year in two large regions of Italy. These findings should inform policymakers in redefining the status of CA as a rare disease, potentially influencing patient care and treatment costs.

AIMS:Myocardial work (MW) estimation by pressure-strain loops using speckle tracking echocardiography (STE) has shown to evaluate left ventricular (LV) contraction overcoming the load-dependency limit of LV global longitudinal strain (GLS). This has proved useful in hemodynamic variation settings e.g. heart failure and valvular heart disease. However, the variation of MW and strain parameters across different stages of primary mitral regurgitation (MR) and its impact on symptoms, which was the aim of our study, has never been investigated. METHODS AND RESULTS:Consecutive patients with mild, moderate and severe MR were prospectively enrolled. Exclusion criteria were: chronic atrial fibrillation, valvular heart prosthesis, previous cardiac surgery. Clinical evaluation, blood sample tests, ECG and echocardiography with STE and MW measurement were performed. Patients were then divided into groups according to MR severity. Differences among the groups and predictors of symptoms (as NYHA class≥2) were explored as study endpoints. Overall, 180 patients were enrolled (60 mild,60 moderate,60 severe MR). LV GLS and global peak atrial longitudinal strain (PALS) reduced according to MR severity. Global constructive work (GCW) and global wasted work (GWW) significantly improved, while global work efficiency (GWE) reduced, in patients with moderate and severe MR. Among echocardiographic parameters, global PALS emerged as the best predictor of NYHA class (p < 0.001;area under curve,AUC = 0.7). CONCLUSIONS:MW parameters accurately describe the pathophysiology of MR, with initial attempt of LV increased contractility to compensate volume overload parallel to the disease progress, although with low efficacy, while global PALS is the most associated with the burden of MR symptoms.

Abstract Introduction In the last decade, peak atrial longitudinal strain (PALS) was ascertained to be superior to conventional echocardiographic indices for secondary cardiovascular (CV) prevention. Purpose Standard and advanced echocardiography including PALS was evaluated to find predictors of prognosis in patients with arterial hypertension and/or diabetes for the optimization of primary CV prevention. Methods Hypertensive and/or diabetic patients >40 years old and in sinus rhythm who underwent a complete cardiological evaluation at our centre in 2008-2015 were retrospectively included. Personal history, physical examination, standard and advanced (speckle tracking) echocardiographic data were collected. The exclusion criteria were previous cv events or cardiac surgery, active pacemaker, more than moderate valvular regurgitation and/or stenosis, missing informed consent. All patients were followed up for a mean time of 11.2±1.3 years for the development of first atrial fibrillation (AF) episode, congestive heart failure hospitalization, transient ischemic attack, stroke, myocardial infarction/coronary revascularization, and CV death. Univariate and multivariable stepwise Cox regressions were performed to estimate Hazard Ratio (HR). Kaplan Meier curves (KM) compared the survival between patients with different ranges of Global PALS. Log-rank test was performed to compare the KM curves. Results This retrospective study included 292 adults (mean age 63.0±9.0 years, 50% female), among which 210 hypertensives and 67 diabetics. Mean left ventricular (LV) ejection fraction (EF) was 58.2±4.9%, mean GLS was -17.0±6.6%, mean left atrial volume was 52.9±24.9ml and mean PALS 29.7±11.1%. During follow up, 110 patients developed at least one cv event: 52 all-cause deaths, 28 CV deaths, 30 heart failure admissions, 31 first AF episode, 18 TIA/strokes, 25 myocardial infarction/revascularization. Dividing the population according to events occurrence, patients with events had similar EF (p= 0.06), while being older (65.8±9.6 vs 61.3±9.0 years) and with a worse diastolic function (E/E’ ratio 10.6±5.0 vs 8.7±3.6), LV longitudinal strain (GLS, -17.7±2.9 vs -15.7±3.4%) and PALS (34.6±9.9 vs 21.6±7.7%, all p <0.001). From univariate statistical analysis, age, E/E’, PAPs, GLS and PALS were all predictors of events, but only age (HR 1.03, p=0.03) and PALS (PALS<22.5% HR 18.99 and PALS 22.5-30 HR 7.68, both p<0.001) remained independently associated with outcome at multivariate analysis. Patients with PALS<22.5 have an event-free survival of 82.4% at 1 year, 49.8% at 5 years and 25.3% at 10 years compared to 100% at 1 year, 98.5% at 5 years and 92.5% at 10 years if PALS PALS>30% (Fig.1). The same results were confirmed in female population (Fig.2). Conclusions If confirmed by larger studies, PALS could be a quick, feasible and reliable part of cardiologic evaluation for prognostic stratification in primary CV prevention in hypertensive and/or diabetic patients.Fig. 1Fig. 2

Abstract Background Sodium-glucose cotransporter type-2 inhibitors (SGLT2i) showed to reduced morbidity andmortality in HF patients. The aim of this study was to assess potential effects of dapagliflozin in non-diabetic patients with heart failure (HF) with reduced and mildly reduced ejection fraction (HFrEF and HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). Methods This randomized, prospective, single-center, open-label trial compared consecutive non-diabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except SGLT2i (Fig.1). Primary endpoint was the modification of left ventricular (LV) global longitudinal strain (GLS), diastolic function (as peak atrial longitudinal strain, PALS) and right ventricular (RV) function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Results Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n=44) or to continue with OMT (n=44). All STE values improved in dapagliflozin group after 6 months, while there was a non-significant improvement in OMT group (Fig.1). Moreover, when comparing the modification of STE parameters at follow up in HFrEF and HFmrEF patients, only the main treatment effect resulted statistically significant in both groups (p<0.0001), indicating a significant difference between dapagliflozin and OMT. Conclusions This study provided randomized data on the beneficial effect of dapagliflozin in non-diabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique i.e. STE. This suggests its usefulness for LV reverse remodeling and better quality of life in patients with HFrEF and HFmrEF.

Advanced heart failure (AdvHF) can only be treated definitively by heart transplantation (HTx), yet problems such right ventricle dysfunction (RVD), rejection, cardiac allograft vasculopathy (CAV), and primary graft dysfunction (PGD) are linked to a poor prognosis. As a result, numerous biomarkers have been investigated in an effort to identify and prevent certain diseases sooner. We looked at both established biomarkers, such as NT-proBNP, hs-troponins, and pro-inflammatory cytokines, and newer ones, such as extracellular vesicles (EVs), donor specific antibodies (DSA), gene expression profile (GEP), donor-derived cell free DNA (dd-cfDNA), microRNA (miRNA), and soluble suppression of tumorigenicity 2 (sST2). These biomarkers are typically linked to complications from HTX. We also highlight the relationships between each biomarker and one or more problems, as well as their applicability in routine clinical practice.

Abstract Background Heart failure (HF) is associated with high mortality and costs mainly due to hospitalizations. Real-world data deriving from registries demonstrate gaps between guidelines recommendations and clinical practice. Purpose The REAL-HF registry aims to provide a comprehensive overview of hospital management of HF patients in Italy, and to identify critical issues and their potential determinants. Methods The registry involves 11 centers, including all adult patients hospitalized for HF in the period 2020-2026. Data are derived from discharge letters and electronic hospital records. Patients are screened based on Diagnosis Related Groups codes. Inclusion criteria are: 1. Hospitalization for HF (except for elective procedures); 2. Decompensated HF in conjunction with other pathological conditions; 3. De novo or decompensated HF during hospitalization due to non-cardiac causes. Results This analysis included 3918 patients over two years (2020-2021) from 4 tertiary hospitals (males 2135 [54%], median age of 80[IQR 71-86] years). Only 39% of patients were hospitalized in a cardiology unit. Hospital length of stay was 9(6-15) days. Median left ventricular ejection fraction (LVEF) was 45(32-55%) (HFrEF n = 1462[37%], HFmrEF n = 420[11%], HFpEF n = 1675[43%]). Coronary artery disease was the leading cause (n = 1082[28%]) of HF, and atrial fibrillation was highly prevalent (history - 22%; during hospitalization - 33%). Arterial hypertension was the most prevalent (71%) cardiovascular risk factor. Chronic kidney disease (47%) and chronic obstructive pulmonary disease (26%) were frequent comorbidities, and they resulted to be independent predictors of adverse outcomes in multiple regression analysis. Only 67% of patients with HFrEF were treated with ACEi/ARB/ARNi, 84% with a beta-blocker, 73% with MRAs, and only 48% with all three drugs classes. New SGLT2i were prescribed in 4%. Only 16% of patients with HFrEF had a defibrillator, and 13% were treated with cardiac resynchronization therapy. Patients hospitalized in non-cardiology units were older (83 vs 73 years, p<0.0001), more frequently females (52% vs 44%, p<0.001), with HFpEF (54% vs 24%, p<0.001), and less frequently treated with ARNi, beta-blockers, or MRAs (p<0.001). Overall 30-days hospital readmission rate was 8.4%, without significant differences between cardiology and non-cardiology units (7.8 vs 8.7%, p = 0.347). However, 1-year rehospitalizations and mortality were significantly higher in patients hospitalized in non-cardiac units (33.4% vs 25.3% and 23% vs 9.57%, respectively - p<0.001). Conclusions The REAL-HF registry confirms the clinical impact of HF, and the poor outcomes of patients hospitalized with this condition. Adherence to the guidelines is still inadequate and this may impact on patients' outcomes. Moreover, the significant differences in terms of patients’ profiles might further increase the gap between highly specialized cardiology units and internal medicine departments.

INTRODUCTION:Amyloid light-chain amyloidosis is a rare condition characterized by the abnormal production of immunoglobulin light chain that misshape and form amyloid fibrils. Over time, these amyloid deposits can accumulate slowly, causing dysfunction in organs and tissues. Early identification is crucial to ensure optimal treatment. We aim to identify a better marker of cardiac amyloidosis, using advanced echocardiography, to improve diagnosis and the timing of available treatments. MATERIALS AND METHODS:108 consecutive hematological patients (32, 30% female and 76, 70% male) with a plasma cell disorder referred to our Cardiological center underwent ECG, first and second-level echocardiography (Speckle Tracking) and complete biochemical profile. The best predictors of ALCA (AUC ≥ 0.8) were included in a further analysis stratified by AL score. RESULTS:At ROC analysis, the best bio-humoral predictors for the diagnosis of ALCA were Nt-pro-BNP (AUC: 0.97; p < 0.01) and Hs-Tn (AUC: 0.87; p < 0.01). Regarding echocardiography, the best diagnostic predictors were left atrial stiffness (LAS) (AUC: 0.83; p < 0.01) for the left atrium; free wall thickness for the right ventricle (AUC: 0.82; <0.01); left ventricular global longitudinal strain (LVGLS) (AUC: 0.92; p < 0.01) and LVMi (AUC 0.80; p < 0.001) for the left ventricle; and AL-score (AUC 0.83 p < 0.01). In patients with AL-SCORE < 1, LAS (AUC 0.86 vs AUC 0.79), LVGLS (AUC 0.92 vs AUC 0.86) and LV mass (AUC 0.91 vs AUC 0.72) had better diagnostic accuracy than patients with higher AL-score (AL SCORE ≥ 1). CONCLUSION:Multi-parametric imaging approach with LVGLS and LAS may be helpful for detecting early cardiac involvement in AL amyloidosis.

Abstract Background Non-invasive myocardial work (MW) is a relatively novel echocardiographic method with increasing fields of application. Normal reference ranges of MW indices in a healthy population have already been determined but these may differ in patients who have undergone a heart transplant (HTX). Purpose To obtain the reference ranges for 2D echocardiographic indices of MW for HTX patients and to compare them with the results of the EACVI NORRE study regarding healthy volunteers. Methods All consecutive HTX patients admitted at our Institution under Day Hospital regimen from September 2019 to May 2022 who performed endomyocardial biopsy (EMB) were considered. Patients with echocardiographic exam or brachial artery cuff pressure unavailability, history of rejection, history of coronary artery vasculopathy (CAV) and either acute cellular rejection (ACR) or acute antibody-mediated rejection (AMR) at EMB were excluded. Non-invasive MW calculation through Speckle-tracking Echocardiography (STE) was retrospectively performed for included patients. Further, MW analysis results were compared to those from the EACVI NORRE study. Results Out of 176 HTX patients who had performed EMB and had available echocardiographic and blood pressure data, 35 patients were excluded because of history of rejection, 4 patients because of history of CAV and 55 patients because of either ACR or AMR at EMB. Therefore, study population consisted of 82 HTX patients (68.3% male, median age 53 (46 – 62) years). Median age from HTX was 5 (2 – 22) months. Mean global work efficiency (GWE, 84 ± 8 %), global work index (GWI, 1447 ± 409 mmHg%), global constructive work (GCW, 2067 ± 423 mmHg%) and median global wasted work (GWW, 310 (217 – 499) mmHg%) did not differ between sex categories (p-value > 0.05). Each of these indices significantly differed from those reported in the EACVI NORRE study (p-value < 0.001), with lower GWI, GCW, GWE and higher GWW in the HTX population. Conclusion This study provides reference ranges for non-invasive MW indices in a HTX population free from transplant-related complications which are different from those regarding a population of healthy volunteers.Table 1

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial work (MW) estimation by pressure-strain loops using an implemented speckle tracking software has showed to estimate LV contractile properties overcoming the load-dependency limit of left ventricular (LV) global longitudinal strain (GLS). This has proved useful particularly in clinical setting characterized by frequent hemodynamic variations, such as heart failure and valvular heart disease. However, the variation of MW parameters across different stages of mitral regurgitation (MR) and its impact on symptoms has never been investigated. Objective The aim of this observational study was to assess the variations of MW and deformation parameters of left heart chambers in mild, moderate and severe MR. Methods Consecutive patients with mild, moderate and severe MR were prospectively enrolled. Exclusion criteria were: chronic atrial fibrillation, valvular heart prosthesis, previous cardiac surgery. Clinical evaluation, blood sample tests, ECG and echocardiography were performed. Speckle tracking analysis completed by myocardial work were performed offline. Patients were then divided into groups first according to MR severity. Differences among the groups were analyzed by student T test (or non-parametric tests for non-normally distributed variables) and predictors of symptoms (as NYHA class ≥ 2) were explored by logistic regression analysis. Results Overall, 120 patients were enrolled (40 mild, 40 moderate, 40 severe MR). LV GLS improved according to severity, while Global PALS reduced according to MR severity. Global constructive work (GCW) and global wasted work (GWW) significantly improved in patients with moderate and severe MR, while global work efficiency (GWE) showed a trend towards reduction in patients with higher grades of MR. Global work index did not change significantly in the three groups (Fig.1). Among strain parameters, global PALS emerged as a predictor of NYHA class (R2=0.2, p<0.001) These results are explained by the pathophysiology of MR, characterized by a mechanism of attempted LV compensation to volume overload with increased contractility parallel to the disease progress, although with low efficacy on increasing LV stroke volume and increased wasted work; while LA and diastolic function have an early reduction which is associated with the occurrence of symptoms. Conclusions Myocardial deformation parameters of the left heart chambers accurately reflect the pathophysiologic mechanisms of MR stages and are associate with the burden of symptoms.

Abstract Funding Acknowledgements Type of funding sources: None. Background left atrial (LA) strain by speckle tracking echocardiography (STE) is gaining increasing evidence as diagnostic and prognostic tool in several clinical settings. However, the lack of a dedicated software was considered one of its main limitations, although many studies proved a good feasibility and reproducibility of a ventricular-based software. Brand-new fully automated software tools dedicated to the LA have been developed, both for on-line use on the echocardiographic machine and for off-line use on the workstation. Purpose The purpose of our study was to compare LA strain measures acquired by the new fully automated dedicated software with the "traditional" semi-automated ventricular based one in healthy, pressure-overloaded, and volume-overloaded patients. Methods Grey scale apical 4-chamber view echocardiographic images acquired by an experienced operator (GE, Vivid E9, Orthern, Norway) in healthy patients, patients with pressure overload (arterial hypertension, aortic stenosis) and pressure-volume overload (mitral regurgitation, heart failure) were analyzed. STE was performed offline by two independent experienced operators, using both the semi-automated and the fully automated Echopac (Milwaukee,Wisconsin) software, which was then compared using matched-pairs analysis. Both operators were blinded to the other measures and repeated the same measurement on the same images after 10 days. Measurement of LA strain was performed on-line on the echocardiographic machine in a selected group of 20 patients by one of the two operators. Patients with prosthetic valves, heart transplantation, atrial fibrillation were excluded. Results Overall, 100 patients were analyzed (41 healthy patients, 28 with pressure overload, 31 with pressure-volume overload). Peak atrial longitudinal strain (PALS) showed a high reproducibility with both methods. However, the dedicated method had a slightly higher inter-operator reproducibility (intraclass correlation coefficient(ICC)=0.97; 95% CI=[0.87;0.99] vs. ICC=0.96 [9.87;0.99] ) (Fig.1) and intra-operator reproducibility (ICC=0.99 [0.99;0.99] vs. 0.98 [0.98;0.99] (Fig.2); correlation=0.85, p<0.001in operator 1 and 0.97 [0.95;0.98] vs. 0.95 [0.92;0.96]; correlation=0.83, p<0.001 in operator 2) with a slightly lower time consumption (90 s vs. 105 s) than the traditional ventricular-based one. On-line software showed a nearly perfect reproducibility with offline software [ICC=0.99 [0.99;1]] with a further time saving (60 vs. 90 s). Conclusions the new fully automated software for the analysis of LA strain has a high inter-operator and intra-operator reproducibility. Both the automated and the traditionally used semi-automated software calculation provided optimal reproducibility and time-consumption, for different categories of subjects, and could be equally chosen for strain calculation in daily clinical practice. On-line LA strain calculation allows a reliable and time-saving measurement.

Abstract Funding Acknowledgements Type of funding sources: None. Background cardiac amyloidosis (CA) is characterized by an impairment of cardiac diastolic and, in the severe state of the disease, systolic function, with increasing worsening of functional capacity and quality of life (QoL). Six minute walking test (6MWT) and Kansas City Cardiomyopathy Questionnaire (KCCQ) are two well-known and validated methods to assess the impact of heart failure (HF) symptoms and functional capacity. Left atrial strain by speckle tracking echocardiography has emerged as an index of left ventricular (LV) diastolic function and filing pressure, and is also associated with symptoms in HF. However, its possible association with functional capacity and QoL in CA has not yet been investigated. Objectives in this observational pilot study, our aim was to evaluate the relationship of left atrial strain with 6MWT and KCCQ in patients with CA (both AL and ATTR). Methods we enrolled consecutive patients with CA during routine follow up visits. Patients underwent clinical and echocardiographic evaluation. On the same day, 6MWT was performed and KCCQ was administered. Speckle tracking analysis was performed offline by an experienced operator blinded to the other data. Correlation analysis was conducted using Pearsons’ coefficient and linear regression analysis Results overall, 43 patients with CA (25 ATTR, 18 AL) were enrolled. Mean age was 74 ±11, 16% (n=7) were female. Most patients showed normal left ventricular (LV) ejection fraction (55±9) and reduced LV global longitudinal strain (GLS =−12 ± 7%), 32 of them with apical sparing pattern (Table 1). Mean global peak atrial longitudinal strain (PALS) was 14 (median[IQR]=6.5;23.5), mean 6MWT score = 382 ± 104 and mean KCCQ score= 67 ± 24. Global PALS showed a strong direct correlation with 6MWT (Fig 1, P= 0.4, R2=0.2, p-value=0.032) and a trend towards correlation with KCCQ (R2=0.3, p-value=0.06), although not reaching statistical significance, probably due to the low sample size. The correlation between PALS and 6MWT was even stronger in patients with ATTR (p = 0.7, R2 0.4; p-value<0.0001). Conclusions our preliminary results show that, global PALS is associated with functional capacity and the burden of HF symptoms in ATTR and AL, suggesting its role as a more objective marker of disease severity in CA.

Abstract Funding Acknowledgements Type of funding sources: None. Background Training-induced cardiac remodelling is usually accompanied by a harmonic and symmetric adaptation of cardiac chambers. Mild aortic enlargement may be a consequence of intense training, although even the definition of aortic dilatation, particularly in athletes and tall athletes, is sometimes challenging. It is therefore essential to early identify competitive athletes with aortic dilatation to manage this condition appropriately. Purpose This study aimed to test a new parameter for the definition of aortic dilatation in competitive athletes, assessing the balancing cardiac remodelling in athletes through the ratio between the aortic diameter and left ventricular (LV) diameter. Methods Competitive athletes were compared with sedentary subjects and with patients with known aortic dilatation. 1901 subjects who underwent echocardiography from 2019 to 2022 were retrospectively enrolled: 993 athletes (74% males, mean age 26±7 years), 410 sedentary (74.1% males, mean age 29±11 years) and 498 patients with aortic dilatation (74.3% males, mean age 56±7 years). Results Patients with aortic dilatation had both an absolute (39.2±2.4 mm) and indexed (19.4±2.2 mm/m2) aortic diameter larger than athletes (30.6±3.2 mm; 16.1±1.5 mm/m2) and sedentary subjects ( 30.5±3.1 mm; 16.5±1.6 mm/m2), with no statistically significant differences between athletes and sedentary subjects. The ratio between the aortic diameter and LV end-diastolic diameter was lower in athletes (0.59 ± 0.06), compared to sedentary subjects (0.65 ± 0.05) and to patients with aortic dilatation (0.81 ± 0.06). The latter had a significantly higher value than the remaining groups (p <0.05). The analysis of the ROC curves highlighted that the cut-off of the ratio between the aortic root diameter and LV diastolic diameter was 0.71, with a 96% sensitivity and 99% specificity of detecting a pathological aortic dilatation. Conclusions This study tested a new echocardiographic parameter for the definition of an aortic dilatation in competitive athletes. The ratio between aortic diameter and LV end-diastolic diameter, with a cut off of 0.71, demonstrated a good sensitivity and specificity to differentiate between physiological and pathological remodelling of the aorta.

Abstract Background ACUTE HF is a multiparametric score combining clinical, biochemical and echocardiographic indexes, which was developed and validated in different studies as prognostic tool in acute heart failure (HF) patients for the prediction of 30-days, 6-months and 5-years mortality after discharge. However, in these critical patients the prediction of in-hospital mortality may be fundamental to guide therapeutic management during hospital stay. Objective The aim of our study was to assess the prognostic value of ACUTE HF score for in-hospital mortality in an external cohort of patients hospitalized for acute HF. Methods Consecutive patients hospitalized for acute HF between 2020 and 2021 in our University Hospital were retrospectively enrolled. Patients with unclear diagnosis of de-novo, decompensated HF or HF reacutization were excluded. Clinical, biohumoral and echocardiographic data were collected. ACUTE HF score was calculated as : 1.4*[serum creatinine>2mg/dl]+0.8*[ejection fraction<30]+ 0.7*[age>76]+0.7*[prior hospitalization for AHF]+0.9*[prior stroke/transient ischemic attack]+0.5*[more than moderate mitral regurgitation]+0.8*[use of non-invasive ventilation]. Then, it was used to divide the population into three risk groups (low risk: ACUTE HF ≤1.5; intermediate risk: 1.5 Results Overall, 1291 patients were included in the present study (age=77±13 years, mean ejection fraction = 41 ± 13%). Median in-hospital follow up was 9 [6;15] days, during which 115 patients died. Patients who died during hospitalization were older, had worse renal function and higher mitral regurgitation severity, and more frequently had arterial hypertension, diabetes mellitus, chronic obstructive pulmonary disease and history of stroke. With ROC curves, it showed to be a good predictor of in-hospital mortality, with an AUC=0.66, which was even higher in patients with preserved ejection fraction (AUC=0.76, Fig.1). With multivariate analysis, ACUTE HF score showed to be a predictor of in-hospital mortality independent from arterial hypertension, diabetes mellitus, chronic kidney disease (OR = 1.5 [C.I. 1.22 – 1.81 each point increase]. Kaplan Meier analysis showed a good risk stratification of study cohort divided into 3 risk groups according to ACUTE HF (Fig.2) Conclusions ACUTE HF score is an independent and reliable predictor of in-hospital mortality in patients hospitalized for acute HF. After multiple external validation, considering its rapid and easy calculation, we suggest its use in the management algorithms of acute HF patients in daily clinical practice.Fig.1Fig.2

Background: Sarcoidosis is a systemic chronic granulomatous disease associated to a significant morbidity and mortality. Speckle tracking echocardiography (STE) has recently emerged as a non-invasive promising tool for the detection of cardiac sarcoidosis. Aim: to investigate the utility of left atrial and left ventricular (LV) longitudinal STE for the prediction of major adverse cardiac events (MACE) and sarcoidosis relapses. Methods: We retrospectively enrolled 172 patients with sarcoidosis (111 females, 57.4 ± 12.6 years old) who underwent STE and pulmonary function tests at Siena Regional Referral Centre for interstitial lung diseases. Results: After a median follow-up of 2217 days, we observed 8 deaths, 23 MACE and 36 disease relapses. Basal LV global longitudinal strain (GLS) was significantly lower in patients with MACE (p = 0.025), with a treshold of < 17.13% identified as a fair predictor of MACE. Concerning the sarcoidosis control, a reduction of the LV ejection fraction (p = 0.0432), tricuspid annular plane systolic excursion (p = 0.0272) and global peak atrial longitudinal strain (PALS, p = 0.0012) were reported in patients with relapses during the follow-up. PALS < 28.5% was the best predictor of a sarcoidosis relapse (Figure). Conclusions: Our results identified LV-GLS and PALS as new non-invasive prognostic markers in sarcoidosis, supporting the use of STE in the clinical management of these patients.

Abstract Background Right ventricular failure (RVF) complicates 10 to 40% of left ventricular assist device (LVAD) implants, with necessity of high dose inotropic/vasodilatory drugs and right ventricular assist devices in severe cases. Prevention of RVF starts with appropriate patient selection for LVAD implant through extensive clinical, echocardiographic and hemodynamic evaluation. Purpose This study aimed to evaluate the performance of a novel non-invasive echocardiographic method for estimation of right ventricular myocardial work to predict RVF and death after LVAD implant. Methods Consecutive patients from May 2017 to February 2022 undergoing LVAD implant were retrospectively reviewed. Patients without a useful echocardiographic exam and/or a right heart catheterization prior to LVAD implant were excluded. Myocardial work analysis by Speckle Tracking Echocardiography (STE) was performed in these patients. The primary endpoints were RVF and death. Results The study included 23 patients (mean age 64±8 years, 91% men). Median follow-up time was 304 days (IQR: 23–1017). GWI significantly correlated with invasively-derived right ventricular stroke work index (RVSWI, r=0.538; p=0.008) and pulmonary arterial compliance (PAC, r=−0.522; p=0.013). Patients who experienced RVF (26.1%) had lower GWI (p=0.047) and GWE (p=0.001) and higher GWW (p=0.001). Patients who experienced death at 30 days after LVAD implant (26.1%) had lower GWE (p=0.005) and higher GWW (p=0.006). Performance for prediction of RVF after LVAD implant was greatest for GWE (AUC 0.92), followed by GWW (AUC 0.88) and GWI (AUC 0.78). A cut-off of 77% for GWE have a 100% sensibility and 82% specificity for prediction of RVF. At long term follow-up, death occurred in 4 patients (29%) in the GWE>77% group and in 6 patients (67%) in the GWE<77% group (hazard ratio for death, 0.24; 95% CI, 0.07 to 0.89, p=0.032). Conclusions Right ventricular myocardial work is a strong predictor of RVF after LVAD implant and death at long-term follow up. Its calculation should be implemented in the evaluation for LVAD candidacy. Funding Acknowledgement Type of funding sources: None.