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.

Takotsubo syndrome (TTS) is an acute and reversible heart failure condition characterized by transitional left ventricular systolic dysfunction without obstructive coronary artery disease. Although sympathetic hyperactivation is considered a key pathogenic mechanism, the contribution of gut-derived endotoxemia and oxidative stress is still unclear. Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria, may translocate from the gut into the bloodstream and increase oxidative stress through activation of NADPH oxidase 2 (NOX2), nitric oxide (NO) depletion and endothelial dysfunction. This study aimed to evaluate circulating LPS levels in TTS and investigate their association with NOX2 activation, oxidative stress, and endothelial dysfunction. Twenty consecutive patients with TTS and 20 age- and sex-matched healthy controls were included. Within 48 h of admission, fasting blood samples were collected to assess soluble NOX2-derived peptide (sNOX2-dp), hydrogen peroxide (H2O2), NO metabolites (NOx), LPS, and zonulin. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Compared with controls, TTS patients had significantly higher serum levels of sNOX2-dp, H2O2, LPS, and zonulin, lower NOx and impaired FMD. sNOX2-dp was positively correlated with LPS (Rs = 0.539, p < 0.001) and zonulin (Rs = 0.331, p = 0.037) and inversely correlated with FMD (Rs = −0.462, p = 0.003). NOx correlated negatively with H2O2, zonulin and LPS. In multivariable analysis, LPS was the only independent predictor of FMD (β = 0.498, SE = 0.126, p = 0.001) and sNOX2-dp (β = −0.572, SE = 0.034 p < 0.001); FMD (β = −0.347, SE = 0.455, p = 0.005), H2O2 (β = 0.445, SE = 0.155, p < 0.001), and zonulin (β = 0.298, SE = 2.309, p = 0.016) emerged as independent predictors of LPS (adjusted R2 = 0.585). TTS is associated with low-grade endotoxemia, NOX2-driven oxidative stress, reduced NO bioavailability, and endothelial dysfunction. The independent association between LPS and NOX2 activation supports a potential gut–vascular axis in TTS pathophysiology.

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.

Background: The aim of this study was to retrospectively compare the results of systematic preoperative coronary angiography ultimately followed by stenting in patients with asymptomatic coronary artery disease (CAD) undergoing open peripheral revascularization for peripheral arterial disease (PAD). Methods: From January 2003 to December 2022, 276 patients having undergone open peripheral recanalization for PAD were retrospectively reviewed and divided into 2 groups. Patients in group A (n-132), all without a history of coronary artery disease, had undergone standard cardiac evaluation (EKG and cardiac ultrasound) and systematic preoperative coronary angiography ultimately followed by percutaneous coronary intervention (PCI) for significant coronary artery stenoses, whereas patients in group B (n-144) had only undergone standard cardiac evaluation prior to open peripheral revascularization. Mean length of follow-up was 60 months (range 12e130 months). The primary endpoints were occurrence of any long-term postoperative myocardial infarction (MI) and any complication related to coronary angiography and stenting. Secondary endpoints were long-term postoperative mortality, complications related to open peripheral revascularization and long-term peripheral bypass patency. Results: Fifty-three patients (40.0%; 95% CI: 32.0%, 48.0%) in group A had a significant coronary artery stenosis, 48(36.3%; 95% CI: 32.0%, 48.0%) underwent percutaneous intervention (PCI) and 5 (3.8%; 95% CI: 0.5%, 7.0%) received coronary artery bypass grafting (CABG) before open revascularization. While no postoperative MI was observed in group A, seven MI occurred in group B (4.9%; 95% CI: 1.4%, 8.4%), one of which was fatal (P = 0.04). During the follow-up period, 2 non-fatal MI (1.5%; 95% CI: 1.2%, 1.8%) occurred in group A, while 20 MI (14.1%; 95% CI: 8.5%, 19.7%) occurred in group B, 5 of which were fatal (P = 0.0001). No com- plications related to coronary angiography , stenting were observed. While no postoperative mortality was observed in group A, 2 patients (1.4%; 95% CI:-0.5%, 3.3%) in group B died, one due to a fatal MI and one due to an acute lower limb ischemia and multiple organ failure (P = 0.17). During follow-up, 7 deaths (5.3%; 95% CI: 1.5%, 9.1%) occurred in group A (5 related to cancer, one to lung disease and one for unknown causes) and 16 (11.0%; 95% CI: 6.0%, 16.0%) in group B (5 related to MI, 8 to cancer , 2 of unknown causes) (P = 0.07). Concerning complications related to open peripheral revascularization, 2 compartmental syn- dromes (1.5%; 95% CI:-0.5%, 2.5%) occurred in group A and 2 (1.4%; 95% CI:-0.5%, 2.5%) in group B (P = 0.93) in group B (P = 0.93), without indication to perform fasciotomy, no prosthetic infection was observed in either group, and one bypass occlusion (0.7%; 95% CI:-0.7%, 2.1%) occurred in group B with acute lower limb ischemia (P = 0.34). Peripheral by- passes were patent in 90 patients in group A (68.0%; 95% CI: 64.0%, 72.0%) and in 96 patients (67%; 95% CI: 59.4%, 74.6%) in group B (P = 0.78). Conclusion: Systematic preoperative coronary angiography ultimately followed by PCI in patients selected for open lower limb revascularization is safe and reduces intraoperative and post- operative risk of MI.

Myocardial infarction (MI) is associated with emotional distress, depression, and anxiety. Defense mechanisms and mentalized affectivity play key roles in affective regulation; however, their roles in individuals with MI remain underexplored. This study examined the relationship between depressive and anxiety symptoms, defensive functioning, and mentalized affectivity in MI patients. Sixty-seven patients with MI and 80 healthy controls completed the DSM-5 Self-Rated Level 2 Cross-Cutting Symptom Measures—Depression and Anxiety—Adult, the Defense Mechanisms Rating Scales-Self-Report-30, and the Brief-Mentalized Affectivity Scale. Multivariate analyses were used to compare the MI and healthy groups, while correlations and mediation models were used to evaluate associations between variables within the MI group. Compared to controls, patients with MI exhibited more severe depressive and anxiety symptoms, maladaptive defenses, and lower levels of mentalized affectivity. Within the MI group, the severity of depressive and anxiety symptoms was associated with immature defensive functioning and poorer abilities to regulate affects. Notably, the relationship between worse defensive functioning and severe depressive and anxiety symptoms was mediated by the capacity to process emotions. The mediating role of this specific dimension of mentalized affectivity emphasizes the potential of affect regulation as a target for tailored psychosocial interventions aimed at improving clinical outcomes.

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.

Background: Performing percutaneous coronary intervention (PCI) and endovascular aneurysm repair (EVAR) at the same time represents a groundbreaking development in the multidisciplinary treatment of cardiovascular disease. This combined PCI–EVAR approach bridges a critical gap by offering treatment for patients who have both coronary artery disease and aortic aneurysms. This innovative strategy exemplifies the evolving landscape of cardiovascular care, providing a new solution for complex clinical situations that previously required separate procedures. Methods: Six patients with critical coronary artery lesions and asymptomatic infrarenal aortic aneurysms (AAAs) ≥ 6 cm diameter, as well as one patient with critical coronary artery lesions and endoleak type 1A with aneurysms ≥ 6 cm, underwent simultaneous coronary artery revascularization through percutaneous intervention (PCI) and endovascular aneurysm repair (EVAR). The occurrence of any intraoperative or postoperative complication was considered to be the primary endpoint of the study, including the abortion or failure of either PCI or EVAR, bleeding requiring a conversion to open surgical procedures, the failure of local anesthesia, postoperative myocardial or lower limb ischemia, and a postoperative serum creatinine level of >125 mmol/L or of >180 mmol/L in patients affected by chronic renal failure. The overall length of the procedure, X-ray exposure, the quantity of iodine contrast medium administered, and the length of recovery were considered to be secondary endpoints. Results: Postoperative complications included two episodes of acute renal failure in the two patients already affected by chronic renal failure, which were easily resolved with adequate daily hydration and the elimination of nephrotoxic drugs. In no cases did cardiac ischemia or lower limb ischemia occur. The average procedure duration was 198 min (range: 180–240 min), the average fluoroscopy duration was 41.7 min (range: 35–50 min), the average amount of iodinated contrast medium was 34.8 mL (range: 30–40 mL), and the mean length of hospitalization was 2.7 days (range: 2–5 days). Conclusions: In selected patients, this surgical approach has demonstrated safety, reduced hospitalization times, minimized risks associated with complications from the untreated condition if procedures were performed at different times, and facilitated the effective management of intraoperative complications due to the presence of a multidisciplinary team. However, the limited number of patients necessitates further research.

Context:Metabolomics is becoming increasingly popular for detecting markers that indicate the presence of a specific disease. However, it is usually applied to studying individual ailments, yielding results that may not be directly relevant to people with multiple health conditions. Objective:Our study proposes a different approach to explore metabolic crosstalk between various disease states. Design Setting and Patients:We conducted a study on subjects at medium to high risk of developing coronary artery disease. We measured the plasma levels of 83 metabolites using nuclear magnetic resonance and analyzed the connections between these metabolites and various risk factors such as diabetes, hypertension, and dyslipidemia. Linear regression and multivariate analysis were combined for this purpose. Results:Inspection of the metabolic maps created by our analysis helped us efficiently compare profiles. In this way, it was possible to discover opposing metabolic features among single conditions and their combination. Furthermore, we found compensating metabolic effects between diabetes, hypertension, and dyslipidemia involving mainly ketone body metabolism and fatty acid β-oxidation. Conclusion:Our study introduces a novel approach to investigating how metabolism reacts to the simultaneous presence of multiple health conditions. This has allowed the detection of potential compensatory effects between diabetes, hypertension, and dyslipidemia, highlighting the complexity of metabolic crosstalk in patients with comorbidities. A better understanding of metabolic crosstalk like this could aid in developing focused treatments, resulting in improved therapeutic results.

Background: New onset atrial fibrillation (NOAF) is associated with worse clinical outcomes after acute coronary syndrome (ACS). Identification of ACS patients at risk of NOAF remains challenging. To test the value of the simple C2HEST score for predicting NOAF in patients with ACS.Methods: We studied patients from the prospective ongoing multicenter REALE-ACS registry of patients with ACS. NOAF was the primary endpoint of the study. The C2HEST score was calculated as coronary artery disease or chronic obstructive pulmonary disease (1 point each), hypertension (1 point), elderly (age & GE; 75 years, 2 points), systolic heart failure (2 points), thyroid disease (1 point). We also tested the mC2HEST score.Results: We enrolled 555 patients (mean age 65.6 & PLUSMN; 13.3 years; 22.9% women), of which 45 (8.1%) developed NOAF. Patients with NOAF were older (p < 0.001) and had more prevalent hypertension (p = 0.012), chronic obstructive pulmonary disease (p < 0.001) and hyperthyroidism (p = 0.018). Patients with NOAF were more frequently admitted with STEMI (p < 0.001), cardiogenic shock (p = 0.008), Killip class & GE;2 (p < 0.001) and had higher mean GRACE score (p < 0.001). Patients with NOAF had a higher C2HEST score compared with those without (4.2 & PLUSMN; 1.7 vs 3.0 & PLUSMN; 1.5, p < 0.001). A C2HEST score > 3 was associated with NOAF occurrence (odds ratio 4.33, 95% confidence interval 2.19-8.59, p < 0.001). ROC curve analysis showed good accuracy of the C2HEST score (AUC 0.71, 95%CI 0.67-0.74) and mC2HEST score (AUC 0.69, 95%CI 065-0.73) in predicting NOAF.Conclusions: The simple C2HEST score may be a useful tool to identify patients at higher risk of developing NOAF after presentation with ACS.

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.

Aortic stenosis (AS) is the most frequent form of valvular heart disease in developed countries, and severe AS is a major cause of morbidity and mortality in the elderly. Since many of these patients often have a high or prohibitive risk for surgical aortic valve replacement (SAVR), transcatheter aortic valve implantation (TAVI) has emerged as an established therapy and is now becoming a common practice, even in low-risk patients. As severe AS and coronary artery disease (CAD) are often concomitant, a matter of debate is whether, how, and when to treat coexisting CAD. The aim of this commentary is to analyze the rationale for the diagnostic evaluation and management of CAD in TAVI candidates, as proposed by the recent EAPCI/ESC consensus statement.