PURPOSE:The aim of this study was to examine the incremental value of three-dimensional transesophageal echocardiography (3DTEE) versus two-dimensional transesophageal echocardiography (2DTEE) in the detection of prosthetic valve endocarditis (PVE), its prognostic value, and its peculiar diagnostic features compared to native valve endocarditis (NVE). METHODS:One hundred and twenty-nine patients with infective endocarditis (64 PVE and 65 NVE), selected from a population of one hundred and ninety-five patients with suspected PVE or NVE, were studied using 3DTEE and 2DTEE. Presence, location and size of vegetations, new or progressive valve regurgitation, perivalvular extension, and new dehiscence of valve prosthesis were assessed. RESULTS:A definite diagnosis of infective endocarditis was obtained by using 2023 Duke-ESC criteria. Significant improvement in global χ2 value was noted with the addition of 3DTEE parameters compared with 2DTEE alone for PVE detection (from 81.7 to 92.3, p=0.002) and for prediction of in-hospital mortality (from 79.3 to 86.7, p=0.01). In patients with prosthetic valves and surgical confirmation of the diagnosis, 2DTEE and 3DTEE showed a sensitivity of 84.8% and 90.1%, a specificity of 74.2% and 84.3% (p=0.001), a positive predictive value of 89.6% and 93.4%, and a negative predictive value of 76.3% and 85.6% (p=0.003) for PVE detection. Regarding the detection of PVE- and NVE-related valvular and perivalvular lesions according to surgery findings, Receiver Operating Characteristic (ROC) curve analysis showed similar diagnostic performance of three-dimensional transesophageal echocardiography (3DTEE) for valvular complications (AUC = 0.727 vs. 0.897, p = 0.704) and superior diagnostic performance for perivalvular complications, both in mechanical and biological prostheses (AUC = 0.831 vs. 0.516, p = 0.012, and AUC = 0.836 vs. 0.697, p = 0.026, respectively). These results were particularly marked in early PVE compared to late PVE (AUC = 0.883 vs. 0.478, p = 0.001). CONCLUSIONS:Our results suggest that 3DTEE provides additional diagnostic and prognostic information for patients with PVE and higher diagnostic performance for perivalvular complications compared to NVE.

Abstract Background Although most patients with early repair of an isolated atrial septal defect (ASD) have resolution of right ventricular (RV) dilatation, some studies show persistent RV dysfunction and reduced maximal exercise capacity in long-term follow-up in a considerable subgroup of patients. Purpose Right ventricular myocardial work (RVMW) is a novel method for non-invasive assessment of right ventricular (RV) function using RV pressure-strain loops. We sought to evaluate RV function by RVMW indexes in adult patients with atrial septal defect (ASD) before and six months after transcatheter closure in order to assess their value compared to RV three-dimensional(3D) volumetric indexes and two-dimensional(2D)-Doppler parameters. Methods Fifteen ASD patients before and after percutaneous closure were studied using a commercially available cardiovascular ultrasound system (Vivid E95, GE Vingmed Ultrasound, Norway). 15 healthy age- and sex-matched subjects were selected as controls. RV volumes and ejection fraction (3D-RVEF) were obtained using a software package (4D Auto RVQ). 2D-Doppler parameters of RV function (fractional area change -FAC-, tricuspid annular plane systolic excursion -TAPSE-, myocardial performance index -MPI-) were calculated. RV global longitudinal strain (RVGLS) was evaluated by tracing the RV free wall and interventricular septum. Pulmonary artery systolic pressure (PASP) was estimated by tracing the tricuspid regurgitation velocity-time integral. RV global work index (RVGWI), RV global constructive work (RVGCW), RV global wasted work (RVGWW), and RV global work efficiency (RVGWE) were analysed. Datasets were digitally stored and analyzed offline using GE EchoPAC Version-R6. Peak oxygen consumption(VO2) derived from symptom-limited treadmill tests was obtained. Results Overall, 3D-RVEF, RVGWI and RVGWE were significantly higher than control group in open ASD (p=0.02) and decreased significantly six months after closure (p=0.03). NYHA class improved from 1.9±0.4 before to 1.2±0.5 after closure (p<0.05). In 5 patients (33%) 3D-RVEF was reduced and RV was dilated compared to controls six months after closure (p=0.04 and p=0.02, respectively). RVGWI was significantly correlated with RVGLS (p<0.001), PASP (p=0.002), and TAPSE (p=0.014). By multivariate analysis RVGWE and 3D-RVEF were independent predictors of functional class. ROC analysis showed RVGWE and 3D-RVEF (AUC 0.8917 and 0.8869, respectively) to be more sensitive predictors of unfavorable outcome after defect closure (VO2 ≤16mL/min/kg) compared to FAC, TAPSE, and MPI (AUC 0.7586, 0.7824, and 0.7963, respectively). Conclusions In ASD patients before and after closure, right ventricular myocardial work provides useful insights into the quantitative assessment of RV function. RVMW findings are comparable to RV-3D volumetric parameters as predictors of impaired exercise impairment and more accurate than 2D parameters.

Abstract Purpose The aim of the present study was to investigate whether systemic arterial hypertension is associated with abnormal left ventricular (LV) function assessed by myocardial work determined by speckle tracking echocardiography and how such changes are related to left ventricular hypertrophy (LVH) and aortic strain. Methods We examined 102 hypertensive (mean age, 65±16 years, 53% male) and 102 sex- and age-matched healthy controls (mean age, 66±14 years, 52% male). The following three-dimensional echocardiographic parameters were evaluated: LV end-diastolic volume, LV end-systolic volume, LV stroke volume, LV ejection fraction (LVEF), LV end-diastolic mass, and LV end-diastolic mass index (LVMI). Hypertensive patients were divided into two groups: patients without LVH (group-A) and patients with LVH (group-B, LVMI>115g/m2 men, LVMI>95g/m2 women). All of them had preserved LV ejection fraction. Global LV longitudinal strain (GLS) was calculated by two-dimensional speckle tracking echocardiography. The following indices of MW were assessed: global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Corrected circumferential ascending aorta strain (AAo-S) was calculated by two-dimensional speckle tracking echocardiography as global aortic strain /pulse pressure. Data analysis was performed offline (GE EchoPAC v.R6). Results In group-A GWI and GCW were increased compared to controls (p=0.04). In group-B GWI and GCW were decreased compared to controls (p=0.01). GWW was increased in group-A(p=0.01) and group-B(p<0.001). GWE was decreased in group-A(p=0.004) and group-B(p<0.001). There was a positive correlation between GWE and AAo-S(r=0.53,p=0.02). GWE was independently associated with GLS(β=0.28,p=0.012), LV mass(β=0.33,p=0.01) and AAo-S(β=0.36,p=<0.01) in the whole hypertensive population. At ROC (receiver operating characteristic) analysis, optimal cutoff values of GWI, GLS, AAo-S, GWE and combination of GWE and AAo-S discriminating LV hypertrophy were 0.7413, 0.7685, 0.8167, 0.8538 and 0.9016, respectively. Conclusions In systemic hypertension, aortic strain assessment improved the ability of myocardial work variables to differentiate patients with LVH, patients without LVH, and control subjects. The decrease in GWE and AAo-S occurred even in the absence of LV hypertrophy.

Due to the high mortality and morbidity of patients with aortic and mitral endocarditis, careful monitoring is necessary to recognize an early failure of antibiotic and cardiokinetic therapy and avoid a possible cardiogenic or septic shock. The timing of surgery is crucial for patients in whom medical therapy fails. The aim of our study is to identify potential echocardiographic biomarkers of adverse events in patients with left-sided native valve infective endocarditis. Sixty-four patients with aortic and/or mitral valve dysfunction(AOVD, MVD) from infective endocarditis were studied by three-dimensional transesophageal echocardiography(3DTEE) and transthoracic speckle tracking echocardiography(3DSTE). Sixty-four healthy subjects were selected as controls. Vegetation size and valvular features were assessed by 3DTEE. Standard transthoracic echocardiographic parameters were determined. Global left ventricular(LV) longitudinal strain(3D-LVGLS) and area strain(3D-LVGAS) were measured by 3DSTE. Averaged LV rotation and rotational velocities from the base and apex were obtained and used for calculation of LV twist and torsion. Endpoints were embolism and in-hospital mortality. Maximal vegetation dimension was 10 (4-29) mm if measured by 3DTEE and 7 (4-20) mm if measured by 2DTEE (p = 0.02). Valvular and perivalvular complications were present in 21(33

Aims:In patients late after correction of tetralogy of Fallot (TOF), the combined effects of pre-operative hypertrophy and hypoxia, ventricular interdependence, acquired post-operative lesions such as pulmonary or aortic regurgitation, and congenital vasculopathy may result in impaired right ventricular (RV) and left ventricular (LV) function. The aim of the present study was to investigate the interventricular interactions in repaired TOF (rTOF) and the impact of aortic function on biventricular performance using two-dimensional (2D-STE) and three-dimensional speckle-tracking echocardiography (3D-STE). Methods and results:Twenty-five adult patients with rTOF and 25 age- and gender-matched healthy controls were studied. LV and RV volumes were determined by 3D-STE and cardiac magnetic resonance. LV and RV longitudinal strains (LVLS and RVLS) and LV and RV area strains (LVAS and RVAS) and LV twist/rotation were calculated by 3D-STE. Ascending aorta circumferential strain (AAo-CS) was obtained using 2D-STE. LV 3D-STE parameters were decreased in rTOF patients compared with controls even in patients with normal ejection fraction. AAo-CS was decreased (6.7 ± 1.9 vs. 10.1 ± 2.6, P = 0.003) in rTOF patients compared with controls even in the presence of normal aortic dimensions and correlated with AAo diameter (r = -0.69, P = 0.0001), LV twist (r = 0.54, P = 0.004), LVAS (r = -0.56, P = 0.003), and RVLS (r = -0.39, P = 0.036). LVAS and AAo-CS were associated with disease severity (peak oxygen consumption and arrhythmia occurrence). Significant improvement in global χ 2 value was noted with RV 3D-STE parameters + LVAS + AAo-CS compared with RV dysfunction alone for detecting exercise capacity impairment (from 77.1 to 84.4 to 91.2, P = 0.003). Conclusion:Speckle-tracking echocardiography revealed subtle LV and AAo dysfunction in adults with rTOF. A correlation was observed between LV and RV strain changes and between AAo strain impairment and LV/RV dysfunction. LV and AAo changes had an incremental value in evaluating disease severity.

Heart rate is a simple and readily promptly available element in a patient's evaluation, but it has fundamental implications in physiopathology both in the healthy subject and in the setting of heart failure. Heart rate is regulated by the discharge rate of cells in the sinoatrial node (which in normal conditions maintains a higher intrinsic rate than other portions of the electrical conduction system of the heart, thus suppressing other potential pacemaker sites by overdrive suppression), which means, in deeper detail, by the duration of the spontaneous diastolic depolarization.

We aimed to comprehensively analyze by three-dimensional speckle-tracking echocardiography (3DSTE) and Doppler echocardiography right ventricular (RV) performance, pulmonary arterial (PA) elastic properties and right ventricular-pulmonary artery coupling (RVPAC) in patients with repaired tetralogy of Fallot (rTOF) and assess the feasibility and clinical utility of related echocardiographic indices. Twenty-four adult patients with rTOF and twenty-four controls were studied. RV end-diastolic volume(3D-RVEDV), RV end-systolic volume(3D-RVESV), RV ejection fraction(3D-RVEF), RV longitudinal strain(3D-RVLS) and RV area strain(3D-RVAS) were calculated by 3DSTE. RV end-systolic area (RVESA) was obtained by planimetry. Pulmonary regurgitation (PR) was assessed as trivial/mild or significant by cardiac magnetic resonance (CMR) and color-Doppler. Pulmonary artery (PA) elastic properties were determined using two-dimensional/Doppler echocardiography. RV systolic pressure (RVSP) was measured using standard Doppler methods. RVPAC was assessed using various 3DSTE-derived parameters (3DRVAS/RVSP, 3DRVLS/RVESA, 3DRVAS/RVESV). Overall, 3DRVEF and 3DRVAS were impaired in rTOF patients compared with controls. PA pulsatility and capacitance were reduced (p = 0.003) and PA elastance was higher (p = 0.0007) compared to controls. PA elastance had a positive correlation with 3DRVEDV (r = 0.64, p = 0.002) and 3DRVAS (r = 0.51, p = 0.02). By ROC (receiver operating characteristics) analysis, 3DRVAS/RVESV, 3DRVAS/RVSP and 3DRVLS/RVESA cutoff values of 0.31%/mmHg, 0.57%/mmHg and 0.86%/mmHg, respectively, had 91%, 88% and 88% sensitivity and 81%, 81% and 79% specificity in identifying exercise capacity impairment. In rTOF patients increased 3DSTE-derived RV volumes and impaired RV ejection fraction and strain are associated with reduced PA pulsatility and capacitance and increased PA elastance. 3DSTE-derived RVPAC parameters using different afterload-markers are accurate indices of exercise capacity.

Background: Contrast-associated acute kidney injury (CA-AKI) is still a major concern for referring physicians, especially in the setting of ST-elevation myocardial infarction (STEMI) patients undergoing primary-PCI (pPCI). To evaluate whether glutathione sodium salt (GSS) infusion impacts favorably on CA-AKI, an unplanned exploratory data analysis of the GSH 2014 trial was performed. Methods: One hundred patients with STEMI were assigned at random to an experimental group (No. 50) or to a placebo group (No. 50). Treatment consisted of an intravenous infusion of GSS lasting over 10 min before p-PCI. The placebo group received the same quantity of normal saline solution. After the interventions, glutathione was administered in the same doses to both groups at 24, 48 and 72 h. Results: CA-AKI occurred in 5 out of 50 patients (10%) allocated to the experimental group (GSS infusion) and in 19 out of 50 patients (38%) allocated to the placebo group (p between groups < 0.001). No patients in either group required renal replacement therapy. After allowing for multiple confounders, GSS administration (OR 0.17, 95% CI 0.04–0.61) and door-to-balloon time (in hours) (OR 1.61, 95% CI 1.01–2.58) have been the only independent predictors of CA-AKI. Conclusions: the results of this sub-study, which show a significant trend towards an improved nephroprotection in the experimental group, led to the hypothesis of a possible new prophylactic approach to counteract CA-AKI using repeated GSS infusion. Subsequent studies with specific clinical outcomes would be necessary to confirm these data.

Right ventricle–pulmonary artery coupling (RVPAC), an application of the previously described left-sided ventriculoarterial coupling, denotes the relationship between right ventricular (RV) contractility and RV afterload. The most accepted RVPAC index is the relationship between ventricular end-systolic elastance (considered equal to the maximum elastance) as a measure of contractility and effective arterial elastance (determined as end-systolic pressure/stroke volume) as a measure of afterload and is obtained invasively using pressure-volume loop analysis. Surrogates of ventricular and arterial elastance were processed through bedside imaging techniques including echocardiography-derived indices of RV function. 1 Guazzi M. Bandera F. Pelissero G. et al. Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis. Am J Physiol Heart Circ Physiol. 2013; 305: H1373-H1381 Crossref PubMed Scopus (359) Google Scholar ,2 Levy P.T. El Khuffash A. Woo K.V. et al. Right ventricular-pulmonary vascular interactions: an emerging role for pulmonary artery acceleration time by echocardiography in adults and children. J Am Soc Echocardiogr. 2018; 31: 962-964 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar RVPAC should also be considered in the setting of repaired tetralogy of Fallot (rTOF) and postoperative pulmonary regurgitation (PR), as previous studies 3 Egbe A.C. Kothapalli S. Miranda W.R. et al. Assessment of right ventricular-pulmonary arterial coupling in chronic pulmonary regurgitation. Can J Cardiol. 2019; 35: 914-922 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar ,4 Cheng S. Li V.W. So E.K. et al. Right ventricular-pulmonary arterial coupling in repaired tetralogy of Fallot. Pediatr Cardiol. 2022; 43: 207-217 Crossref PubMed Scopus (2) Google Scholar confirmed impaired pulmonary artery (PA) vascular distensibility in rTOF regardless of residual RV outflow tract (RVOT) obstruction and commonly used echocardiographic or cardiac magnetic resonance parameters of RV function do not provide information on the adequacy of apparently normal RV function for a given afterload. Three-dimensional (3D) speckle-tracking echocardiography (STE) allows quantification of RV volumes and RV ejection fraction (RVEF) as well as assessment of RV wall strain without ventricular geometric assumptions. 5 Vitarelli A. Mangieri E. Terzano C. et al. Three-dimensional echocardiography and 2D-3D speckle tracking imaging in chronic pulmonary hypertension: Diagnostic accuracy in detecting hemodynamic signs of RV failure. J Am Heart Assoc. 2015; 4: e001584 Crossref PubMed Scopus (99) Google Scholar ,6 Li Y. Zhang L. Gao Y. et al. Comprehensive assessment of right ventricular function by three-dimensional speckle-tracking echocardiography: comparisons with cardiac magnetic resonance imaging. J Am Soc Echocardiogr. 2021; 34: 472-482 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar Measurements of RV volumes using 3D STE recently showed accuracy and reproducibility 6 Li Y. Zhang L. Gao Y. et al. Comprehensive assessment of right ventricular function by three-dimensional speckle-tracking echocardiography: comparisons with cardiac magnetic resonance imaging. J Am Soc Echocardiogr. 2021; 34: 472-482 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar but were not tested specifically in rTOF patients or tested for RV afterload. Since abnormal afterload is present in this population, we hypothesized that the RVPAC index obtained using 3D STE-derived parameters may better correlate with exercise capacity than standalone RV systolic indices or other RVPAC indices.

The occurrence of Contrast-Associated Acute Kidney Injury (CA-AKI) in patients with ST-Elevation Myocardial Infarction (STEMI) has a negative impact on the length of hospital stay and mortality. Reactive Oxygen Species (ROS) release, along with vasoconstriction and hypoperfusion, play a key role in its development. To date, there is still no validated prophylactic therapy for this disease. The use of antioxidants, based on experimental and clinical studies, looks promising. Taking into consideration previous literature, we speculate that an early, combined and prolonged intravenous administration of both Glutathione (GSH) and ascorbic acid in STEMI patients undergoing primary Percutaneous Coronary Intervention (pPCI) may be of value in counteracting the occurrence of CA-AKI. We aimed at evaluating this hypothesis by applying a multicenter research protocol, using a double-blind randomized, placebo-controlled trial design. The primary endpoint will be to test the efficacy of this combined antioxidant therapy in reducing the occurrence of renal damage, in patients with acute myocardial infarction treated with pPCI. Furthermore, we will investigate the effect of the study compounds on changes in oxidative stress markers and platelet activation levels through bio-humoral analyses.

BACKGROUND: Developing strategies aimed to shorten the length of stay (LOS) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) is a healthcare goal to be pursued. We carried out a subanalysis of the GSH 2014 Trial to assess the potentiality of glutathione sodium salt infusion to impact on LOS.METHODS: 100 consecutive patients with STEMI, aged more than 18 years and referred to the three enrolling centers for primary angioplasty (p-PCI), were asked to participate to the GSH 2014 Trial. Fifty patients were randomized to treatment group and fifty to placebo; treatment consisted into an intravenous infusion of glutathione sodium salt over 10 minutes before p-PCI; after interventions, glutathione was infused at the same doses at 24, 48 and 72 h elapsing time. A stepwise linear multivariate model was built in order to assess independent predictors of LOS.RESULTS: Subjects receiving infusion of glutathione sodium salt had a significantly lower LOS than subjects receiving placebo (8.6±3 vs. 10.8±4 days, P=0.006). At multivariate analysis, the randomization to GSH group was negatively associated with length of stay (β±SEβ -1.64±0.74, cumulative R2 0.43, P=0.03) independently from age, sex, cardiovascular risk factors, number of treated vessels, infarct-related coronary artery (left anterior descending artery as reference) and enrolment hospital.CONCLUSIONS: Results from this subanalysis support the hypothesis that an early and prolonged glutathione sodium salt administration, as antioxidant therapy to patients with STEMI, may favorably impact on LOS. Further studies with larger sample size are necessary to confirm these data.

The aim of this study was to describe the pattern, characteristics, and outcomes of infective endocarditis (IE) in Yemen and compare the results with the findings of a Western university hospital. Patients (pts) with a final diagnosis of IE observed in Al-Thawra Sanaa Cardiac Center were prospectively enrolled in 1-year time period. Clinical and diagnostic findings were compared to clinical and diagnostic data of 50 pts with IE observed at Sapienza University Hospital in Rome, Italy. The mean age was 38 +/- 6. Predisposing factors for IE were rheumatic heart disease (RHD) in 34 pts (68%), congenital heart disease in 9 pts (18%), prosthetic valve IE in 4 pts (8%), and previous IE in 3 pts (6%). Transthoracic echocardiography (TTE) was done in 50 pts and transesophageal echocardiography (TEE) in 25. Blood cultures were taken in all pts and were positive in 3 pts (6%) and negative in 47 (94%). TTE was positive in 34/50 pts (68%) and TEE in 20/25 (80%). Compared to Sapienza University pts, Al-Thawra Cardiac Center pts had a younger age (p = 0.003), more predisposing RHD (p = 0.0004), less prosthetic heart valves IE (p = 0.002), and more negative blood cultures (p = 0.0001). IE is still a common disease in Yemen among RHD pts and affects the younger age group. It has severe complications which need early diagnosis and proper management. Echocardiography is of prime diagnostic value in the absence of positive blood cultures. An effort should be made to prevent rheumatic fever and RHD.

Ischemia-Reperfusion Injury (IRI) is responsible for adverse outcomes in patients with ST-Elevation Myocardial Infarction (STEMI). Oxidative stress, resulting from the production of Reactive Oxygen Species (ROS) and low availability of Glutathione (GSH), are the two main mediators of IRI. The effectiveness of exogenous antioxidant therapy in this scenario is still debated, since the encouraging results obtained in animal models have not been fully reproduced in clinical studies. In this review we focus on the role of GSH, specifically on the biomolecular mechanisms that preserve myocardial cells from damage due to reperfusion. In this regard, we provide an extensive discussion about GSH intrinsic antioxidant properties, its current applications in clinical practice, and the future perspectives.

Abstract Funding Acknowledgements Type of funding sources: None. Purpose. In mitral valve prolapse (MVP), preoperative assessment of repairability depends primarily on the complexity of the prolapse and is one of the most challenging roles of the echocardiologist. The aim of this study was to investigate whether three-dimensional transesophageal echocardiography helps in the evaluation of both valvar/annular and ventricular aspects in simple (single segment) and complex (multisegmental) MVP. Methods. We studied 24 patients with mitral regurgitation due to MVP using three-dimensional transesophageal echocardiography. Mitral valve (MV), left atrium (LA) and left ventricle (LV) were analyzed. Leaflets surface area, mitral annulus antero-posterior and inter-commissural diameters, area and circumference were determined. Mitral annular disjunction (MAD) defined as a separation between LA-MV junction and LV attachment was evaluated. Papillary muscle to annulus plane distances and inter-papillary distance were obtained. LV global longitudinal and circumferential strain was assessed by speckle tracking echocardiography. Results. Thirteen patients had complex MVP and 11 had simple MVP. Prolapse volume was 6.37 ± 4.68 mL in complex MVP and 1.59 ± 1.21 mL in simple MVP (p = 0.004). Prolapse height was 10.1 ± 2.9 mm in complex MVP and 5.8 ± 3.2 mm in simple MVP (p = 0.003). Volume/height ratio was 0.58 ± 0.29 in complex MVP and 0.21 ± 0.14 in simple MVP (p = 0.001). LV longitudinal strain had a negative correlation with change in prolapse height (r = 0.58, p < 0.001), whereas LV circumferential strain correlated with change in prolapse volume (r = 0.53, p < 0.005). Annular area was 1037 ± 191mm2 in simple MVP and 1842 ± 336mm2 in complex MVP (p < 0.01). MAD was evident in 8 complex MVP patients (61%) and 2 simple MVP patients (18%, p < 0.05). The 3D extension of MAD was significantly related to total (r = 0.54; p = 0.002) and anterior leaflet surface area (r = 0.52; p = 0.004), length from papillary muscles to coaptation (r = 0.61; p = 0.002) and regurgitant orifice (r = 0.66; p < 0.001). Conclusions. In MVP patients 3DTEE helps to refine the characterization of simple and complex prolapse by a combined assessment of leaflets/annular details and ventricular attachment.

Introduction: Dyssynchrony indices based on two-dimensional speckle tracking echocardiography have demonstrated added value in identifying patients with mitral valve prolapse (MVP) with a higher prevalence of arrhythmic complications and the potential for sudden cardiac death, but measurements are restricted to a single plane, and complex left ventricular (LV) dyssynchrony patterns may be overlooked. Hypothesis: The purpose of this study was to investigate whether three-dimensional speckle-tracking echocardiography helps in detecting MVP at higher arrhythmic risk. Methods: We studied 21 arrhythmic MVP patients (group 1) with a history of complex ventricular ectopy on holter and/or event monitor (n=17) or defibrillator implant (n=2), 21 MVPs with no arrhythmic complications (group 2) and 21 healthy controls (group 3). 3D LV longitudinal strain (3DE-LVLS) and area strain (3DE-LVAS) were determined (17 segments). 3D LV dyssynchrony index (3DE-LVDI) was obtained as the standard deviation of the times to peak area strain in 17 segments, normalized to RR interval. Results: MVP patients had significantly higher LV dyssynchrony index compared to controls (9.4±3.9% vs 4.3±2.5%, p=0.002) although they had similar LV ejection fraction (64% vs 61%, p=0.51). Group 1 and group 2 had similar LV ejection fraction and clinical data (p>0.05). Bileaflet prolapse was more frequent in group 1 pts (52% vs 24%, p=0.03). Moderate mitral regurgitation was present in 9/21 group 1 pts and 3/21 group 2 pts (p=0.04). Group 1 pts had greater LV dyssynchrony index when compared with group 2 (10.7±4.1% vs 5.1±2.9%, p=0.0001). By ROC (receiver operating characteristics) curves, 3DE-LVDI and 3DE-LVAS cutoff values of 10.2% and -23.8%, respectively, had 89% and 85% sensitivity and 79% and 76% specificity in identifying the presence of significant arrhythmias with areas under the curve 0.87 and 0.84. Conclusions: Impairment of LV deformation parameters determined by three-dimensional speckle tracking echocardiography may help detect increased arrhythmic risk in patients with MVP.

Background Glutathione is a water‐soluble tripeptide with a potent oxidant scavenging activity. We hypothesized that glutathione administration immediately before and after primary angioplasty (primary percutaneous coronary intervention) could be effective in modulating immune cell activation, thereby preventing infarct expansion. Methods and Results One hundred consecutive patients with ST‐segment–elevation myocardial infarction, scheduled to undergo primary percutaneous coronary intervention were randomly assigned before the intervention to receive an infusion of glutathione (2500 mg/25 mL over 10 minutes), followed by drug administration at the same doses at 24, 48, and 72 hours elapsing time or placebo. Total leukocytes, NOX2 (nicotinamide adenine dinucleotide phosphate oxidase 2) activation, NO bioavailability, cTpT (serum cardiac troponin T), hsCRP (high‐sensitivity C‐reactive protein), and TNF‐α (tumor necrosis factor α) levels were measured. Left ventricular size and function were assessed within 120 minutes, 5 days, and 6 months from percutaneous coronary intervention. Following reperfusion, a significant reduction of neutrophil to lymphocyte ratio (P<0.0001), hsCRP generation (P<0.0001), NOX2 activation (P<0.0001), TNF‐α levels (P<0.001), and cTpT release (P<0.0001) were found in the glutathione group compared with placebo. In treated patients, blunted inflammatory response was linked to better left ventricular size and function at follow‐up (r=0.78, P<0.005). Conclusions Early and prolonged glutathione infusion seems able to protect vital myocardial components and endothelial cell function against harmful pro‐oxidant and inflammatory environments, thus preventing maladaptive cardiac repair and left ventricular adverse remodeling. Registration URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2014‐004486‐25.