A Digital Approach to Improve Infection Screening Among Solid Organ Transplant Candidates.

BACKGROUND: Pretransplant infection screening (IS) of potential organ recipients is essential to optimal outcome of solid organ transplantation (SOT). METHODS: A pre-post study was performed during 2020-2023 to investigate the impact of the STREAM (Solid organ TRansplant stEwArdship and Multidisciplinary approach) intervention to improve IS in SOT. The intervention, performed in 2022, included the implementation of IS through educational meetings, local guidelines, and the availability of a digital screening tool. The objective of the study was the assessment of IS completion, including a list of 17 laboratory tests and the investigation of vaccination status. The reduction of unnecessary tests was also analyzed. The test of proportions and a multilevel multivariate Poisson regression model were used to compare IS completion before and after STREAM. infectious diseases (ID) consultation and urgent evaluation were investigated as predictors of IS completion. RESULTS: A total of 171 patients were enrolled, including liver (44%), heart (32%), and kidney (24%) transplant candidates. Mean age was 56 ± 11 years, and most patients (77%) were males. Ninety-five (56%) patients were included before the intervention and 76 (44%) after STREAM. IS completion increased after STREAM (IRR 1.41, p < 0.001) with significant improvement recorded for seven (39%) IS items. Unnecessary tests decreased by 43% after the intervention. ID consultation (IRR 1.13, p = 0.02) and urgent evaluation (p = 0.68, p < 0.001) were predictors of IS improvement. CONCLUSIONS: STREAM was successful in improving IS completion. Further research is needed to investigate the impact of this intervention on posttransplant infections.

Diabetic Cardiomyopathy: Role of Cell Death, Exosomes, Fibrosis and Epicardial Adipose Tissue.

Diabetic cardiomyopathy (DCM) represents one of the typical complications associated with diabetes. It has been described as anomalies in heart function and structure, with consequent high morbidity and mortality. DCM development can be described by two stages; the first is characterized by left ventricular hypertrophy and diastolic dysfunction, and the second by heart failure (HF) with systolic dysfunction. The proposed mechanisms involve cardiac inflammation, advanced glycation end products (AGEs) and angiotensin II. Furthermore, different studies have focused their attention on cardiomyocyte death through the different mechanisms of programmed cell death, such as apoptosis, autophagy, necrosis, pyroptosis and ferroptosis. Exosome release, adipose epicardial tissue and aquaporins affect DCM development. This review will focus on the description of the mechanisms involved in DCM progression and development.

Five-Year Outcome After Continuous Flow LVAD With Full-Magnetic (HeartMate 3) Versus Hybrid Levitation System (HeartWare): A Propensity-Score Matched Study From an All-Comers Multicentre Registry.

Despite the withdrawal of the HeartWare Ventricular Assist Device (HVAD), hundreds of patients are still supported with this continuous-flow pump, and the long-term management of these patients is still under debate. This study aims to analyse 5 years survival and freedom from major adverse events in patients supported by HVAD and HeartMate3 (HM3). From 2010 to 2022, the MIRAMACS Italian Registry enrolled all-comer patients receiving a LVAD support at seven Cardiac Surgery Centres. Out of 447 LVAD implantation, 214 (47.9%) received HM3 and 233 (52.1%) received HVAD. Cox-regression analysis adjusted for major confounders showed an increased risk for mortality (HR 1.5 [1.2-1.9]; p = 0.031), for both ischemic stroke (HR 2.08 [1.06-4.08]; p = 0.033) and haemorrhagic stroke (HR 2.6 [1.3-4.9]; p = 0.005), and for pump thrombosis (HR 25.7 [3.5-188.9]; p < 0.001) in HVAD patients. The propensity-score matching analysis (130 pairs of HVAD vs. HM3) confirmed a significantly lower 5 years survival (81.25% vs. 64.1%; p 0.02), freedom from haemorrhagic stroke (90.5% vs. 70.1%; p < 0.001) and from pump thrombosis (98.5% vs. 74.7%; p < 0.001) in HVAD cohort. Although similar perioperative outcome, patients implanted with HVAD developed a higher risk for mortality, haemorrhagic stroke and thrombosis during 5 years of follow-up compared to HM3 patients.

Corrigendum: Five-Year Outcome After Continuous Flow LVAD With Full-Magnetic (HeartMate 3) Versus Hybrid Levitation System (HeartWare): A Propensity-Score Matched Study From an All-Comers Multicentre Registry.

[This corrects the article DOI: 10.3389/ti.2023.11675.].

Validation of a new model of selective antegrade cerebral perfusion with circulatory arrest in rats.

BACKGROUND: Selective antegrade cerebral perfusion (SACP) is adopted as an alternative to deep hypothermic circulatory arrest (DHCA) during aortic arch surgery. However, there is still no preclinical evidence to support the use of SACP associated with moderate hypothermia (28-30°C) instead of DHCA (18-20°C). The present study aims to develop a reliable and reproducible preclinical model of cardiopulmonary bypass (CPB) with SACP applicable for assessing the best temperature management. MATERIALS AND METHODS: A central cannulation through the right jugular vein and the left carotid artery was performed, and CPB was instituted.Animals were randomized into two groups: normothermic circulatory arrest without or with cerebral perfusion (NCA vs SACP). EEG monitoring was maintained during CPB. After 10 min of circulatory arrest, rats underwent 60 min of reperfusion. After that, animals were sacrificed, and brains were collected for histology and molecular biology analysis. RESULTS: Power spectral analysis of the EEG signal showed decreased activity in both cortical regions and lateral thalamus in all rats during the circulatory arrest. Only SACP determined complete recovery of brain activity and higher power spectral signal compared to NCA (p < 0.05). Histological damage scores and western blot analysis of inflammatory and apoptotic proteins like caspase-3 and Poly-ADP ribose polymerase (PARP) were significantly lower in SACP compared to NCA. Vascular endothelial growth factor (VEGF) and RNA binding protein 3 (RBM3) involved in cell-protection mechanisms were higher in SACP, showing better neuroprotection (p < 0.05). CONCLUSIONS: SACP by cannulation of the left carotid artery guarantees good perfusion of the whole brain in this rat model of CPB with circulatory arrest. The present model of SACP is reliable, repeatable, and not expensive, and it could be used in the future to achieve preclinical evidence for the best temperature management and to define the best cerebral protection strategy during circulatory arrest.

Cellular and Molecular Mechanisms Activated by a Left Ventricular Assist Device.

Left ventricular assist devices (LVADs) represent the final treatment for patients with end-stage heart failure (HF) not eligible for transplantation. Although LVAD design has been further improved in the last decade, their use is associated with different complications. Specifically, inflammation, fibrosis, bleeding events, right ventricular failure, and aortic valve regurgitation may occur. In addition, reverse remodeling is associated with substantial cellular and molecular changes of the failing myocardium during LVAD support with positive effects on patients' health. All these processes also lead to the identification of biomarkers identifying LVAD patients as having an augmented risk of developing associated adverse events, thus highlighting the possibility of identifying new therapeutic targets. Additionally, it has been reported that LVAD complications could cause or exacerbate a state of malnutrition, suggesting that, with an adjustment in nutrition, the general health of these patients could be improved.

Twenty-Year Experience with Surgery for Native and Prosthetic Mitral Valve Endocarditis.

Background and Objectives: To evaluate the early and long-term results of surgical treatment of isolated mitral native and prosthetic valve infective endocarditis. Materials and Methods: All patients undergoing mitral valve repair or replacement for infective endocarditis at our institution between January 2001 and December 2021 were included in the study. The preoperative and postoperative characteristics and mortality of patients were retrospectively reviewed. Results: A total of 130 patients, 85 males and 45 females, with a median age of 61 ± 14 years, underwent surgery for isolated mitral valve endocarditis during the study period. There were 111 (85%) native and 19 (15%) prosthetic valve endocarditis cases. Fifty-one (39%) patients died during the follow-up, and the overall mean patient survival time was 11.8 ± 0.9 years. The mean survival time was better in patients with mitral native valve endocarditis compared to patients with prosthetic valve endocarditis (12.3 ± 0.9 years vs. 8 ± 1.4 years; p = 0.1), but the difference was not statistically significant. Patients who underwent mitral valve repair had a better survival rate compared to patients who had mitral valve replacement (14.8 ± 1.6 vs. 11.3 ± 1 years; p = 0.06); however, the difference was not statistically significant. Patients who underwent mitral valve replacement with a mechanical prosthesis had a significantly better survival rate compared to patients who received a biological prosthesis (15.6 ± 1.6 vs. 8.2 ± 0.8 years; p < 0.001). Patients aged ≤60 years had significantly better survival compared to patients aged >60 years (17.1 ± 1.1 vs. 8.2 ± 0.9; p < 0.001). Multivariate analysis showed that the patient's age >60 years at the time of surgery was an independent risk factor for mortality, while mitral valve repair was a protective factor. Eight (7%) patients required reintervention. Freedom from reintervention was significantly higher in patients with mitral native valve endocarditis compared to patients with prosthetic valve endocarditis (19.3 ± 0.5 vs. 11.5 ± 1.7 years; p = 0.04). Conclusions: Surgery for mitral valve endocarditis is associated with considerable morbidity and mortality. The patient's age at the time of surgery represents an independent risk factor for mortality. Mitral valve repair should be the preferred choice whenever possible in suitable patients affected by infective endocarditis.

Impact on Renal Function and Hospital Outcomes of an Individualized Management of Cardiopulmonary Bypass in Congenital Heart Surgery: A Pilot Study.

During cardiopulmonary bypass (CPB), high flows can allow an adequate perfusion to kidneys, but, on the other hand, they could cause emboli production, increased vascular pressure, and a more intense inflammatory response, which are in turn causes of renal damage. Along with demographic variables, other intra-operative management and post-operative events, this might lead to Acute kidney injury (AKI) in infants undergoing cardiac surgery. The aim of our study was to investigate if a CPB strategy with flow requirements based on monitoring of continuous metabolic and hemodynamic parameters could have an impact on outcomes, with a focus on renal damage. Thirty-four consecutive infants and young children undergoing surgery requiring CPB, comparable as for demographic and patho-physiological profile, were included. In Group A, 16 patients underwent, for a variable period of 20 min, CPB aiming for the minimal flow that could maintain values of MVO2 > 70% and frontal NIRS (both left and right) > 45%, and renal NIRS > 65%. In Group B, 18 patients underwent nominal flows CPB. Tapered CPB allowed for a mean reduction of flows of 34%. No difference in terms of blood-gas analysis, spectroscopy trend, laboratory analyses, and hospital outcome were recorded. In patients developing AKI (20%), renal damage was correlated with demographic characteristics and with renal NIRS during the first 6 h in the ICU. A safe individualized strategy for conduction of CPB, which allows significant flow reduction while maintaining normal hemodynamic and metabolic parameters, does not impact on renal function and hospital outcomes.

Mesothelial/monocytic incidental cardiac excrescence in autoimmune disease.

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare benign finding made of mesothelial cells, histiocytes, and fibrin, usually found during heart valve surgery. The clinical relevance resides in the potential misdiagnosis as metastatic carcinoma or arterial embolism. The pathogenesis remains uncertain, with artifactual and reactive hypotheses. Here we present a case of MICE with paradigmatic clinical, imaging, and histological features in a 28-year-old woman with undifferentiated connective tissue disease without previous cardiac catheterization with possible pathogenesis, highlighting the importance of awareness of the existence of this lesion in patients with autoimmune disease.

Selective versus standard cerebro-myocardial perfusion in neonates undergoing aortic arch repair: A multi-center study.

The results of neonatal aortic arch surgery using cerebro-myocardial perfusion were analyzed. Selective cerebral and myocardial perfusion, using two separate pump rotors, was compared with standard perfusion, using a single pump rotor with an arterial line Y-connector. Between May 2008 and May 2016, 69 consecutive neonates underwent arch repair using either selective cerebro-myocardial perfusion (Group A, n = 34) or standard perfusion (Group B, n = 35). The groups were similar for age, weight, BSA, prevalence of one-stage or staged repair, and single ventricle palliation; male gender was more frequent in Group A. The duration of the cerebro-myocardial perfusion was comparable (27 ± 8 vs. 28 ± 7 min, P = 0.9), with higher flows in Group A (57 ± 27 vs. 39 ± 19 mL/kg/min, P = 0.01). Although cardioplegic arrest was more common in Group B (13/34 vs. 23/35, P = 0.03), the duration of myocardial ischemia was longer in Group A (64 ± 41 vs. 44 ± 14 min, P = 0.04). There was 1 hospital death in each group, with no permanent neurological injury in either group. Cardiac morbidity (1/34 vs. 7/35, P = 0.02) was more common in Group B, while extracardiac morbidity was similar in both the groups. During follow-up (3.2 ± 2.4 years), 5 late deaths occurred with a comparable 5-year survival rate (75 ± 17% vs. 88 ± 6%, P = 0.7) and freedom from arch reintervention (86 ± 6% vs. 84 ± 7%, P = 0.6). Risk of cardiac morbidity was greater with standard cerebro-myocardial perfusion (OR = 5.2, CI 3.3-6.8, P = 0.001) and with perfusion flows less than 50 mL/kg/min (OR 3.7, CI 1.87-5.95, P = 0.04). Cerebro-myocardial perfusion is a safe and effective strategy to protect the brain and heart in neonates undergoing arch repair. Selective techniques using higher perfusion flows may further attenuate cardiac morbidity.

Fingolimod Plays Role in Attenuation of Myocardial Injury Related to Experimental Model of Cardiac Arrest and Extracorporeal Life Support Resuscitation.

BACKGROUND: Sudden cardiac arrest is a major global health concern, and survival of patients with ischemia-reperfusion injury is a leading cause of myocardial dysfunction. The mechanism of this phenomenon is not well understood because of the complex pathophysiological nature of the disease. Aim of the study was to investigate the cardioprotective role of fingolimod in an in vivo model of cardiac arrest and resuscitation. METHODS: In this study, an in vivo rat model of cardiac arrest using extracorporeal membrane oxygenation resuscitation monitored by invasive hemodynamic measurement was developed. At the beginning of extracorporeal life support (ECLS), animals were randomly treated with fingolimod (Group A, n = 30) or saline (Group B, n = 30). Half of the animals in each group (Group A1 and B1, n = 15 each) were sacrificed after 1 h, and the remaining animals (Group A2 and B2) after 24 h of reperfusion. Blood and myocardial tissues were collected for analysis of cardiac features, inflammatory biomarkers, and cell signaling pathways. RESULTS: Treatment with fingolimod resulted in activation of survival pathways resulting into reduced inflammation, myocardial oxidative stress and apoptosis of cardiomyocytes. This led to significant improvement in systolic and diastolic functions of the left ventricle and improved contractility index. CONCLUSIONS: Sphingosine1phosphate receptor activation with fingolimod improved cardiac function after cardiac arrest supported with ECLS. Present study findings strongly support a cardioprotective role of fingolimod through sphingosine-1-phosphate receptor activation during reperfusion after circulatory arrest.

Selective Cerebro-Myocardial Perfusion in Complex Neonatal Aortic Arch Pathology: Midterm Results.

Aortic arch repair in newborns and infants has traditionally been accomplished using a period of deep hypothermic circulatory arrest. To reduce neurologic and cardiac dysfunction related to circulatory arrest and myocardial ischemia during complex aortic arch surgery, an alternative and novel strategy for cerebro-myocardial protection was recently developed, where regional low-flow perfusion is combined with controlled and independent coronary perfusion. The aim of the present retrospective study was to assess short-term and mid-term results of selective and independent cerebro-myocardial perfusion in neonatal aortic arch surgery. From April 2008 to August 2015, 28 consecutive neonates underwent aortic arch surgery under cerebro-myocardial perfusion. There were 17 male and 11 female, with median age of 15 days (3-30 days) and median body weight of 3 kg (1.6-4.2 kg), 9 (32%) of whom with low body weight (<2.5 kg). The spectrum of pathologies treated was heterogeneous and included 13 neonates having single-stage biventricular repair (46%), 7 staged biventricular repair (25%), and 8 single-ventricle repair (29%). All operations were performed under moderate hypothermia and with a "beating heart and brain." Average cardiopulmonary bypass time was 131 ± 64 min (42-310 min). A period of cardiac arrest to complete intra-cardiac repair was required in nine patients (32%), and circulatory arrest in 1 to repair total anomalous pulmonary venous connection. Average time of splanchnic ischemia during cerebro-myocardial perfusion was 30 ± 11 min (15-69 min). Renal dysfunction, requiring a period of peritoneal dialysis was observed in 10 (36%) patients, while liver dysfunction was noted only in 3 (11%). There were three (11%) early and two late deaths during a median follow-up of 2.9 years (range 6 months-7.7 years), with an actuarial survival of 82% at 7 years. At latest follow-up, no patient showed signs of cardiac or neurologic dysfunction. The present experience shows that a strategy of selective and independent cerebro-myocardial perfusion is safe, versatile, and feasible in high-risk neonates with complex congenital arch pathology. Encouraging outcomes were noted in terms of cardiac and neurological function, with limited end-organ morbidity.

Blood transfusions may impair endothelium-dependent vasodilatation during coronary artery bypass surgery.

OBJECTIVE: The hemolytic product free-hemoglobin (fHb) reduces nitric oxide (NO) bioavailability. The present study aims to establish whether administration of different blood transfusions result in increased circulating fHb levels and NO consumption with effects on arterial NO-dependent blood flow in patients undergoing CABG surgery. METHODS: Ninety-five consecutive patients undergoing elective CABG surgery were prospectively divided in four groups based on blood transfusion requirements during surgery: stored blood cells (SBC, n. 21), intraoperative autologous salvaged blood (ASB, n. 25), SBC and ASB (n.22), no transfusion (control, n. 27). Blood samples were collected before and after intervention to analyse plasma levels of fHb and NO consumption. Endothelium-dependent relaxation was assessed in left internal mammary artery (LIMA) rings harvested before chest closure. Peripheral artery tonometry was assessed after intervention. RESULTS: Transfusions with SBC increased plasma fHb (p<0.05). Transfusions of ASB resulted in higher plasma fHb compared to SBC (p<0.01). fHb concentrations directly correlated with NO consumption (r=0.65, p<0.001). Maximal endothelium-dependent relaxation in LIMA was significantly attenuated in SBC and ASB patients compared to control (15.2±3.1% vs 21.1±2.5% vs 43±5.0% respectively; p<0.01). Significant correlations were identified between the aortic pressure wave velocity, plasma fHb concentration and NO consumption (p<0.01). CONCLUSIONS: Intraoperative blood transfusions and particularly autologous salvaged blood impair endothelium-dependent relaxation through NO scavenging by fHb. These findings obtained in vitro and in vivo provide new insights into the adverse relation between blood transfusions and patient outcome.

Twenty-Year Outcome After Right Ventricular Outflow Tract Repair Using Heterotopic Pulmonary Conduits in Infants and Children.

Durability of pulmonary conduits (PCs) used for reconstruction of the right ventricular outflow tract (RVOT) may be affected by a variety of factors. Among these, the technique used for PC implantation, whether in orthotopic or heterotopic position, strictly dependent upon the underlying anatomy, has been suggested to influence long-term outcome after RVOT repair. To determine the outcome of heterotopic implantation in infants and children treated at our institution, late results of heterotopic PC in non-Ross patients were analyzed and compared with data of orthotopic PC in age-matched pediatric Ross patients operated during the same time period. Between November 1991 and January 2015, 58 infants and children, 32 male and 26 female, with a median age of 9.4 years (range 1 day-18 years) underwent implantation of heterotopic PC (31 homografts [HG] and 27 xenografts [XG]) for reconstruction of RVOT. Median age in the XG group was significantly lower than in the HG group (0.9 vs. 13.4 years, P = 0.01), while male/female ratio was similar. Fifty (86%) patients had undergone one or more prior cardiac operations, while 32 (55%) required associated procedures during PC implantation. Comparison with data in 305 children and with a median age of 9.4 years, receiving orthotopic PC between 1990 and 2012 (Italian Pediatric Ross Registry), was undertaken. Descriptive, univariate, and Kaplan-Meier analysis defined outcome. There were three (5.2%) early and five (9.0%) late deaths, during a median follow-up of 7.6 years (range 2 months-23 years). Patients having XG had trend toward higher hospital mortality (2/27 vs. 1/31, P = 0.2), but similar late mortality (2/24 vs. 3/30, P = 0.3). Overall survival was 88 and 62%, while freedom from PC replacement was 49 and 21%, at 10 and 20 years, respectively. The latter proved significantly worse than freedom from orthotopic PC replacement, which was 94 ± 2 and 70 ± 9% at 10 and 20 years (P = 0.02). When stratified for type of heterotopic PC, late survival proved comparable (81 and 81% for XG vs. 92 and 60% for HG, at 10 and 20 years, respectively, P = 0.7). However, freedom from PC replacement was significantly higher in patients with heterotopic HG (21 and 5% for XG vs. 63 and 48% for HG, at 10 and 20 years, respectively, P = 0.001). RVOT repair using either XG or HG in heterotopic position is a safe procedure associated with low hospital mortality and satisfactory late survival. Freedom from reoperation is significantly lower than that observed in age-matched children having orthotopic HG. Freedom from reoperation in heterotopic XG is poorer than in HG, although different baseline demography may have influenced this finding.

Improved Outcome of Cardiac Extracorporeal Membrane Oxygenation in Infants and Children Using Magnetic Levitation Centrifugal Pumps.

Extracorporeal membrane oxygenation (ECMO) has traditionally been and, for the most part, still is being performed using roller pumps. Use of first-generation centrifugal pumps has yielded controversial outcomes, perhaps due to mechanical properties of the same and the ensuing risk of hemolysis and renal morbidity. Latest-generation centrifugal pumps, using magnetic levitation (ML), exhibit mechanical properties which may have overcome limitations of first-generation devices. This retrospective study aimed to assess the safety and efficacy of veno-arterial (V-A) ECMO for cardiac indications in neonates, infants, and children, using standard (SP) and latest-generation ML centrifugal pumps. Between 2002 and 2014, 33 consecutive neonates, infants, and young children were supported using V-A ECMO for cardiac indications. There were 21 males and 12 females, with median age of 29 days (4 days-5 years) and a median body weight of 3.2 kg (1.9-18 kg). Indication for V-A ECMO were acute circulatory collapse in ICU or ward after cardiac repair in 16 (49%) patients, failure to wean after repair of complex congenital heart disease in 9 (27%), fulminant myocarditis in 4 (12%), preoperative sepsis in 2 (6%), and refractory tachy-arrhythmias in 2 (6%). Central cannulation was used in 27 (81%) patients and peripheral in 6. Seven (21%) patients were supported with SP and 26 (79%) with ML centrifugal pumps. Median duration of support was 82 h (range 24-672 h), with 26 (79%) patients weaned from support. Three patients required a second ECMO run but died on support. Seventeen (51%) patients required peritoneal dialysis for acute renal failure. Overall survival to discharge was 39% (13/33 patients). All patients with fulminant myocarditis and with refractory arrhythmias were weaned, and five (83%) survived, whereas no patient supported for sepsis survived. Risk factors for hospital mortality included lower (<2.5 kg) body weight (P = 0.02) and rescue ECMO after cardiac repair (P = 0.03). During a median follow-up of 34 months (range 4-62 months), there were three (23%) late deaths and two late survivors with neurological sequelae. Weaning rate (5/7 vs. 21/26, P = NS) and prevalence of renal failure requiring dialysis (4/7 vs. 13/26, P = NS) were comparable between SP and ML ECMO groups. Patients supported with ML had a trend toward higher hospital survival (1/7 vs. 12/26, P = 0.07) and significantly higher late survival (0/7 vs. 10/26, P = 0.05). The present experience shows that V-A ECMO for cardiac indications using centrifugal pumps in infants and children yields outcomes absolutely comparable to international registry (ELSO) data using mostly roller pumps. Although changes in practice may have contributed to these results, use of ML centrifugal pumps appears to further improve end-organ recovery and hospital and late survival.

Continuous Metabolic Monitoring in Infant Cardiac Surgery: Toward an Individualized Cardiopulmonary Bypass Strategy.

Cardiopulmonary bypass (CPB) in infants is associated with morbidity due to systemic inflammatory response syndrome (SIRS). Strategies to mitigate SIRS include management of perfusion temperature, hemodilution, circuit miniaturization, and biocompatibility. Traditionally, perfusion parameters have been based on body weight. However, intraoperative monitoring of systemic and cerebral metabolic parameters suggest that often, nominal CPB flows may be overestimated. The aim of the study was to assess the safety and efficacy of continuous metabolic monitoring to manage CPB in infants during open-heart repair. Between December 2013 and October 2014, 31 consecutive neonates, infants, and young children undergoing surgery using normothermic CPB were enrolled. There were 18 male and 13 female infants, aged 1.4 ± 1.7 years, with a mean body weight of 7.8 ± 3.8 kg and body surface area of 0.39 m(2) . The study was divided into two phases: (i) safety assessment; the first 20 patients were managed according to conventional CPB flows (150 mL/min/kg), except for a 20-min test during which CPB was adjusted to the minimum flow to maintain MVO2>70% and rSO2>45% (group A); (ii) efficacy assessment; the following 11 patients were exclusively managed adjusting flows to maintain MVO2>70% and rSO2>45% for the entire duration of CPB (group B). Hemodynamic, metabolic, and clinical variables were compared within and between patient groups. Demographic variables were comparable in the two groups. In group A, the 20-min test allowed reduction of CPB flows greater than 10%, with no impact on pH, blood gas exchange, and lactate. In group B, metabolic monitoring resulted in no significant variation of endpoint parameters, when compared with group A patients (standard CPB), except for a 10% reduction of nominal flows. There was no mortality and no neurologic morbidity in either group. Morbidity was comparable in the two groups, including: inotropic and/or mechanical circulatory support (8 vs. 1, group A vs. B, P = 0.07), reexploration for bleeding (1 vs. none, P = not significant [NS]), renal failure requiring dialysis (none vs. 1, P = NS), prolonged ventilation (9 vs. 4, P = NS), and sepsis (2 vs. 1, P = NS). The present study shows that normothermic CPB in neonates, infants, and young children can be safely managed exclusively by systemic and cerebral metabolic monitoring. This strategy allows reduction of at least 10% of predicted CPB flows under normothermia and may lay the ground for further tailoring of CPB parameters to individual patient needs.

Chronic overcirculation-induced pulmonary arterial hypertension in aorto-caval shunt.

Pulmonary arterial hypertension is a common complication of congenital heart defects with left-to-right shunts. Current preclinical models do not reproduce clinical characteristics of shunt-related pulmonary hypertension. Aorto-caval shunt was firstly described as a model of right ventricle volume overload. The pathophysiology and the possible determination of pulmonary arterial hypertension of different periods of shunt exposure are still undefined. A method to create standardized, reproducible aorto-caval shunt was developed in growing rats (260±40 g). Three groups of animals were considered: shunt exposure for 10 weeks, shunt exposure for 20 weeks and control (sham laparotomy). Echocardiography and magnetic resonance revealed increased right ventricular end diastolic area in shunt at 10 weeks compared to control. Hemodynamic analysis demonstrated increased right ventricular afterload and increased effective pulmonary arterial elastance (Ea) in shunt at 20 weeks compared to control (1.29±0.20 vs. 0.14±0.06 mmHg/µl, p=0.004). At the same time point, the maximal slope of end-systolic pressure-volume relationship (Ees) decreased (0.5±0.2 mmHg/ml vs. 1.2±0.3, p<0.001). Consequently, right ventricular-arterial coupling was markedly deteriorated with a ≈50% decrease in the ratio of end-systolic to pulmonary artery elastance (Ees/Ea). Finally, left ventricular preload diminished (≈30% decrease in left ventricular end-diastolic volume). Histology demonstrated medial hypertrophy and small artery luminal narrowing. Chronic exposure to aorto-caval shunt is a reliable model to produce right ventricular volume overload and secondary pulmonary arterial hypertension. This model could be an alternative with low mortality and high reproducibility for investigators on the underlying mechanisms of shunt-related pulmonary hypertension.

S-Nitroso Human Serum Albumin Enhances Left Ventricle Hemodynamic Performance and Reduces Myocardial Damage after Local Ischemia-Reperfusion Injury.

Endothelial nitric oxide (NO) production is crucial in maintaining vascular homeostasis. However, in the context of ischemia-reperfusion (I/R) injury, uncoupled endothelial nitric oxide synthase (eNOS) can exacerbate reactive oxygen species (ROS) generation. Supplementation with S-nitroso human serum albumin (S-NO-HSA) offers a potential solution by mitigating eNOS uncoupling, thereby enhancing NO bioavailability. In a study conducted at the University of Verona, male rats underwent thoracotomy followed by 30 min left anterior descendant coronary (LAD) occlusion and subsequent reperfusion. Hemodynamic parameters were meticulously assessed using a conductance catheter inserted via the carotid artery. The rats were stratified into two main groups based on reperfusion duration and the timing of drug infusion, with the effects of S-NO-HSA evaluated after 2 or 24 h. Remarkably, intravenous administration of S-NO-HSA, initiated before or during ischemia, exhibited notable benefits. It significantly improved left ventricular function, safeguarded energetic substrates such as phosphocreatine and ATP, and sustained glutathione levels akin to basal conditions, indicative of diminished oxidative stress. The data from this study strongly suggest a protective role for S-NO-HSA in mitigating I/R injury induced by LAD artery occlusion, a phenomenon observed at both 2 and 24 h post-reperfusion. These findings underscore the promising therapeutic potential of NO supplementation in alleviating myocardial damage subsequent to ischemic insult.

Image-Based Computational Fluid Dynamics to Compare Two Repair Techniques for Mitral Valve Prolapse.

OBJECTIVE : The treatment of mitral valve prolapse involves two distinct repair techniques: chordal replacement (Neochordae technique) and leaflet resection (Resection technique). However, there is still a debate in the literature about which is the optimal one. In this context, we performed an image-based computational fluid dynamic study to evaluate blood dynamics in the two surgical techniques. METHODS : We considered a healthy subject (H) and two patients (N and R) who underwent surgery for prolapse of the posterior leaflet and were operated with the Neochordae and Resection technique, respectively. Computational Fluid Dynamics (CFD) was employed with prescribed motion of the entire left heart coming from cine-MRI images, with a Large Eddy Simulation model to describe the transition to turbulence and a resistive method for managing valve dynamics. We created three different virtual scenarios where the operated mitral valves were inserted in the same left heart geometry of the healthy subject to study the differences attributed only to the two techniques. RESULTS : We compared the three scenarios by quantitatively analyzing ventricular velocity patterns and pressures, transition to turbulence, and the ventricle ability to prevent thrombi formation. From these results, we found that the operative techniques affected the ventricular blood dynamics in different ways, with variations attributed to the reduced mobility of the Resection posterior leaflet. Specifically, the Resection technique resulted in turbulent forces, related with the risk of hemolysis formation, up to 640 Pa, while the other two scenarios exhibited a maximum of 240 Pa. Moreover, in correspondence of the ventricular apex, the Resection technique reduced the areas with low velocity to 15%, whereas the healthy case and the Neochordae case maintained these areas at 30 and 48%, respectively. Our findings suggest that the Neochordae technique developed a more physiological flow with respect to the Resection technique. CONCLUSION: Resection technique gives rise to a different direction of the mitral jet during diastole increasing the ability to washout the ventricular apex preventing from thrombi formation, but at the same time it promotes turbulence formation that is associated with ventricular effort and risk of hemolysis.