Use of point-of-care ultrasound (POCUS) to monitor neonatal and pediatric extracorporeal life support.

Extracorporeal membrane oxygenation (ECMO) is an invasive life support technique that requires a blood pump, an artificial membrane lung, and vascular cannulae to drain de-oxygenated blood, remove carbon dioxide, oxygenate, and return it to the patient. ECMO is generally used to provide advanced and prolonged cardiopulmonary support in patients with refractory acute cardiac and/or respiratory failure. After its first use in 1975 to manage a severe form of meconium aspiration syndrome with resultant pulmonary hypertension, the following years were dominated by the use of ECMO to manage neonatal respiratory failure and limited to a few centers across the world. In the 1990s, evidence for neonatal respiratory ECMO support increased; however, the number of cases began to decline with the use of newer pharmacologic therapies (e.g., inhaled nitric oxide, exogenous surfactant, and high-frequency oscillatory ventilation). On the contrary, pediatric ECMO sustained steady growth. Combined advances in ECMO technology and bedside medical management have improved general outcomes, although ECMO-related complications remain challenging. Point-of-care ultrasound (POCUS) is an essential tool to monitor all phases of neonatal and pediatric ECMO: evaluation of ECMO candidacy, ultrasound-guided ECMO cannulation, daily evaluation of heart and lung function and brain perfusion, detection and management of major complications, and weaning from ECMO support.  Conclusion: Based on these considerations and on the lack of specific guidelines for the use of POCUS in the neonatal and pediatric ECMO setting, the aim of this paper is to provide a systematic overview for the application of POCUS during ECMO support in these populations. What is Known: • Extracorporeal membrane oxygenation (ECMO) provides advanced cardiopulmonary support for patients with refractory acute cardiac and/or respiratory failure and requires appropriate monitoring. • Point-of-care ultrasound (POCUS) is an accessible and adaptable tool to assess neonatal and pediatric cardiac and/or respiratory failure at bedside. What is New: • In this review, we discussed the use of POCUS to monitor and manage at bedside neonatal and pediatric patients supported with ECMO. • We explored the potential use of POCUS during all phases of ECMO support: pre-ECMO assessment, ECMO candidacy evaluation, daily evaluation of heart, lung and brain function, detection and troubleshooting of major complications, and weaning from ECMO support.

Echocardiographic Parameters and Mortality in Pediatric Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to investigate the prognostic value of echocardiographic parameters in pediatric septic patients. DATA SOURCES: MEDLINE, PubMed, and EMBASE (last update April 5, 2020). STUDY SELECTION: Observational studies of pediatric sepsis providing echocardiographic parameters in relation to mortality. DATA EXTRACTION: Echocardiography data were categorized as those describing left ventricular systolic or diastolic function, right ventricular function, and strain echocardiography parameters. Data from neonates and children were considered separately. Analysis is reported as standardized mean difference and 95% CI. DATA SYNTHESIS: We included data from 14 articles (n = 5 neonates, n = 9 children). The fractional shortening was the most commonly reported variable (11 studies, n = 555 patients) and we did not identify an association with mortality (standardized mean difference 0.22, 95% CI [-0.02 to 0.47]; p = 0.07, I2 = 28%). In addition, we did not find any association with mortality also for left ventricular ejection fraction (nine studies, n = 417; standardized mean difference 0.06, 95% CI [-0.27 to 0.40]; p = 0.72, I2 = 51%), peak velocity of systolic mitral annular motion determined by tissue Doppler imaging wave (four studies, n = 178; standardized mean difference -0.01, 95% CI [-0.34 to 0.33]; p = 0.97, I2 = 0%), and myocardial performance index (five studies, n = 219; standardized mean difference -0.51, 95% CI [-1.10 to 0.08]; p = 0.09, I2 = 63%). However, in regard to left ventricular diastolic function, there was an association with mortality for higher early wave of transmitral flow/peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging ratio (four studies, n = 189, standardized mean difference -0.45, 95% CI [-0.80 to -0.10]; p = 0.01, I2 = 0%) or lower peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging wave (three studies, n = 159; standardized mean difference 0.49, 95% CI [0.13-0.85]; p = 0.008, I2 = 0%). We did not find any association with mortality for early wave of transmitral flow/late (atrial) wave of trans-mitral flow ratio (six studies, n = 273; standardized mean difference 0.28, 95% CI [-0.42 to 0.99]; p = 0.43, I2 = 81%) and peak velocity of systolic mitral annular motion determined by tissue Doppler imaging wave measured at the tricuspid annulus (three studies, n = 148; standardized mean difference -0.18, 95% CI [-0.53 to 0.17]; p = 0.32, I2 = 0%). Only a few studies were conducted with strain echocardiography. CONCLUSIONS: This meta-analysis of echocardiography parameters in pediatric sepsis failed to find any association between the measures of left ventricular systolic or right ventricular function and mortality. However, mortality was associated with higher early wave of transmitral flow/peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging or lower peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging, indicating possible importance of left ventricular diastolic dysfunction. These are preliminary findings because of high clinical heterogeneity in the studies to date.

Cardiac Output Measurement With Echocardiography and Pressure Recording Analytical Method in Pediatric Patients Admitted to the Cardiac Intensive Care Unit: A Retrospective Assessment of Bias Between the Two Methods.

OBJECTIVES: This study aimed to compare, in a cohort of critically ill children with biventricular anatomy and no cardiovascular shunt, cardiac output (CO) and cardiac index (CI) assessed by echocardiography and a continuous pulse-contour method, MostCareUP, to measure the differences between these techniques (biasCO and biasCI), and their association with clinical variables. DESIGN: Retrospective study. SETTING: Tertiary pediatric cardiac intensive care unit. PARTICIPANTS: Children admitted to the pediatric cardiac intensive care unit who underwent echocardiography with CO measurement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-five patients were included. BiasCO was -0.02 (0.26) L/min (percentage error 36%). BiasCI was 0.07 (0.34) L/min/m2 (percentage error 18%). Biases and percentage errors were higher in 24 nonsupervised echocardiographies. A negative biasCO (overestimation by MostCareUP) was associated with post-surgical status (v cardiomyopathy), higher systolic arterial pressure, and spontaneous breathing (v intubation). When only absolute values were considered, biasCONONEG correlated with age, weight, arterial pressure, and heart rate, whereas biasCINONEG was associated with a femoral arterial cannula, no use of inotropes, and the absence of mechanical ventilation. After adjustment, biasCONONEG remained independently associated with patients' body weight(p = 0.0001). BiasCINONEG showed a nonlinear relationship with weight below 20 kg and above 40 kg. CONCLUSIONS: Children with extreme low or high weights, those who are extubated, and those with a femoral cannula carry the highest bias. When younger patients are considered, CI should be evaluated instead of CO, because biases are better highlighted by indexing data on body surface area. In children, both echocardiography and MostCareUP may be responsible of inaccurate CO/CI assessment.

Long-term veno-arterial extracorporeal membrane oxygenation as a bridge to heart-lung transplant.

En bloc heart-lung transplantation still represents definitive therapy for end-stage cardiopulmonary failure. However, patients may critically decompensate while awaiting suitable donor organs and necessitate veno-arterial extracorporeal membrane oxygenation. In this article, we describe the combined use of central cannulation with the Berlin Heart EXCOR ventricular assist device cannulae and the CentriMag centrifugal pump as an extended bridge to heart-lung transplantation in three pediatric patients.

Ventricular-Arterial Coupling in Children and Infants With Congenital Heart Disease After Cardiopulmonary Bypass Surgery: Observational Study.

OBJECTIVES: Ventricular-arterial coupling represents the interaction between the left ventricle and the arterial system. Ventricular-arterial coupling is measured as the ratio between arterial elastance and ventricular end-systolic elastance. Scant information is available in critically ill children about these variables. The aim of this study was to prospectively assess ventricular-arterial coupling after pediatric cardiac surgery and evaluate its association with other commonly recorded hemodynamic parameters. DESIGN: Single-center retrospective observational study. SETTING: Pediatric cardiac surgery operating room. PATIENTS: Children undergoing corrective cardiac surgery. INTERVENTIONS: Hemodynamic monitoring with transesophageal echocardiography. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients with biventricular congenital heart disease, who underwent elective cardiac surgery with cardiopulmonary bypass, were enrolled before operating room discharge. Chen single-beat modified method was applied to calculate ventricular-arterial coupling. The median arterial elastance and end-systolic elastance values were 5.9 mm Hg/mL (2.2-9.3 mm Hg/mL) and 4.3 mm Hg/mL (1.9-8.3 mm Hg/mL), respectively. The median ventricular- arterial coupling was 1.2 (1.1-1.6). End-systolic elastance differences between patients with a ventricular-arterial coupling below (low ventricular-arterial coupling) and above (high ventricular-arterial coupling) the median value were -5.2 (95% CI, -6.28 to -0.7; p = 0.008). Differently, arterial elastance differences were -2.1 (95% CI, -5.7 to 1.6; p = 0.19). Ventricular-arterial coupling showed a significant association with pre-ejection time (r, 0.44; p = 0.02), total ejection time (r, -0.41; p = 0.003), cardiac cycle efficiency (r, -0.46; p = 0.02), maximal delta pressure over delta time (r, -0.44; p = 0.02), ejection fraction (r, -0.57; p = 0.01), and systemic vascular resistances indexed (0.56; p = 0.003). After adjustment, total ejection time (p = 0.001), pre-ejection time (p = 0.02), and ejection fraction (p = 0.001) remained independently associated with ventricular-arterial coupling. CONCLUSIONS: Median ventricular-arterial coupling values in children after cardiac surgery appear high (above 1). Uncoupling was particularly evident in high ventricular-arterial coupling patients who showed the lowest end-systolic elastance values (but not significantly different arterial elastance values) compared with low ventricular-arterial coupling. Ventricular-arterial coupling appears to be inversely proportional to pre-ejection time, total ejection time, and ejection fraction.

Is the New Infant Jarvik 2015 Suitable for Patients<8 kg? In Vitro Study Using a Hybrid Simulator.

Our aim was to study the feasibility of implanting the Infant Jarvik 2015 in patients weighing less than 8 kg. The Infant Jarvik 2015 left ventricular assist device (LVAD) was tested in a hybrid simulator of the cardiovascular system reproducing specific patients' hemodynamics for different patient weights (2-7 kg). For each weight, the sensitivity of the pump to different circulatory parameters (peripheral resistance, left ventricular elastance, right ventricular elastance, heart rate, and heart filling characteristics) has been tested repeating for each experiment a pump ramp (10 000-18 000 rpm). The increase in the pump speed causes a decrease (increase) in the left (right) atrial pressure, an increase (decrease) in the arterial systemic (pulmonary) pressure, an increase in the right ventricular pressure, a decrease (increase) in the left (right) ventricular volume, a decrease in the left ventricular cardiac output, an increase in the LVAD output and an increase in the right ventricular cardiac output (total cardiac output). Suction was observed for lower weight patients and for higher pump speed in the case of vasodilation, left ventricular recovery, bradycardia, right ventricular failure, and left ventricular hypertrophy. Backflow was observed in the case of left ventricular recovery at lower pump speed. In the hybrid simulator, the Infant Jarvik 2015 could be suitable for the implantation in patients lower than 8 kg because of the stability of the device respect to the cardio/circulatory changes (low frequency of suction and backflow) and because of the capability of the device to maintain adequate patient hemodynamics.

Predicting the pressure of the total cavopulmonary connection: clinical testing of a mathematical equation.

INTRODUCTION: Some authors advocate the use of a dedicated formula to predict the Fontan pressure starting from pre-Fontan catheterisation data. This paper aims at testing the predictive value of the mentioned formula through a retrospective clinical study. METHODS AND RESULTS: Pre-Fontan catheterisation data and Fontan pressure measured at the completion were retrospectively collected. Pre-Fontan data were used to calculate the predicted pressure in the Fontan system. The predicted values were compared to the Fontan pressure measured at the Fontan completion and with the needs for fenestration. One hundred twenty-four Fontan patients were retrospectively enrolled (At Fontan: median age 30.73 [24.70-37.20] months, median weight 12.00 [10.98-14.15] kg). Fontan conduit was fenestrated in 78 patients. A poor correlation (r2 = 0.05128) between the measured and predicted data for non-fenestrated patients was observed. In the case of Fontan-predicted pressure <17.59 mmHg, the formula identified a good short-term clinical outcome with a sensitivity of 92%. CONCLUSION: The proposed formula showed a poor capability in estimating the actual pressure into the Fontan system and in identifying patients needing fenestration. As the pressure into the Fontan system is determined by multiple factors, the tested formula could be an additional data in a multi-parametric approach.

Evolution of Biventricular Loading Condition in Pediatric LVAD Patient: A Prospective and Observational Study.

The aim of this study was to describe the echocardiographic trend of left ventricular (LV) and right ventricular (RV) function after implantation of a pulsatile flow left ventricular assist device (LVAD) in children. From 2013 to 2016, we prospectively evaluated 13 consecutive pediatric Berlin Heart EXCOR LVAD patients. Clinical and echocardiographic data were collected at baseline, within 24 h after implantation and monthly until LVAD explant. Median age and weight at the implantation was 8 (4-23) months and 5 (4.6-8.3) kg at the time of implantation, respectively. All were affected by dilated cardiomyopathy. Average LVAD support time was 226.2 ± 121.2 days. Nine (70%) were transplanted, 4 (30%) died. LV end-systolic and end-diastolic volumes were reduced until the follow up of two months (P = 0.019 and P = 0.001). A progressive increase in RV dimensions was observed. After 4 months of follow up, RV fractional area change worsening was statistically related with the deterioration of LV unloading (P = 0.0036). Four patients needed prolonged inotropic support for RV failure. Pulsatile LVAD in pediatrics is followed by an early and mid-term LV unloading, as expressed by a decrease in LV volumes and diameters at echocardiogram. The effects of unloading do not remain stable at long term follow up. RV function improved in the acute phase, but a progressive dilatation of RV was noted over time. In some patients, RV failure might lead to the need of an increase of inotropic support at long term follow up.

A New 2D Echocardiographic Approach to Evaluate the Membrane and Valve Movement of the Berlin Heart EXCOR VAD Chamber in Pediatric VAD Patients.

The use of Berlin Heart EXCOR VAD (BH) is a validated therapy to bridge pediatric patients to heart transplant. Serial echocardiographic (ECHO) assessment of VAD patients is necessary to support patients' management. This work aims at developing an innovative strategy to evaluate the BH device functioning by ECHO and its interaction with the native heart in a pediatric population. ECHO evaluation of BH membrane movement, and inflow and outflow valves was performed in 2D, 2D-color Doppler, M-mode, and M-mode color Doppler to assess the functioning of the device by direct positioning of the ECHO probe on the BH cannulas and membranes. Forty Berlin Heart EXCOR VAD were analyzed in 18 patients. Seven BH were placed as RVAD and 33 as LVAD. Results evidenced that 14 (21) inflow (outflow) valves presented a mild regurgitation, while 5 inflow (3 outflow) valves presented a moderate regurgitation. In three cases, we observed severe valve regurgitation with back flow in the left ventricle/right atrium. In both cases, the BH chambers were substituted, but we observed that in one case the regurgitation was due to cannulas compression, while in the other case it was due to valve malfunctioning. The M-mode and the ECHO of the membranes and valves permitted to appreciate the beat phenomenon to assess if the native heart and the BH are working in opposite or in the same phase. The membrane ECHO permits evaluation of minimal changes in membrane movement to assure the completely empty-completely fully work modality. Systematic ECHO assessment of BH chamber might support the BH programming and the detection of anomalous VAD-heart interaction.

Concurrent use of continuous and pulsatile flow Ventricular Assist Device on a fontan patient: A simulation study.

The aim of this work is to develop and test a lumped parameter model of the cardiovascular system to simulate the concurrent use of pulsatile (PVAD) and continuous flow (CVAD) ventricular assist device (VAD) on Fontan patients. Echocardiographic and hemodynamic data of five Fontan patients were retrospectively collected and used to simulate the patients' baseline hemodynamics. Then, for each patient, the following assistance modality was simulated for the cavopulmonary and the single ventricle (SV): (a) CVAD for cavopulmonary assistance (RCF) and PVAD assisting the SV (LCF) (RPF + LCF), (b) CVAD assisting SV and PVAD for cavopulmonary assistance (LPF + RCF). The numerical model can well reproduce patients' baseline. The cardiac output increases more importantly in the LCF + RPF configuration (35 vs. 8%). Ventricular volume decreases more evidently in the configuration LCF + RPF (28 vs. 6%), atrial pressure decreases in the LCF + RPF modality (10%), while it slightly increases in the RCF + LPF modality. The pulmonary arterial pressure slightly decreases (increases) in the configuration RCF + LPF (LCF + RPF). Ventricular external work increases in both configurations because of the total increment of the cardiac output. However, artero-ventricular coupling improves in both configurations: RCF + LPF-14%, LCF + RPF-41%. The pulsatility index decreases (increases) by 8% (13.8%) in the configuration LCF + RPF (RCF + LPF). A model could permit us to simulate extreme physiological conditions of the implantation of both CF and PF VAD on the Fontan patient and could permit to choose the proper VAD on the base of patients' condition. The configuration LCF + RPF seems to maximize the hemodynamic benefits.

Application of a Lumped Parameter Model to Study the Feasibility of Simultaneous Implantation of a Continuous Flow Ventricular Assist Device (VAD) and a Pulsatile Flow VAD in BIVAD Patients.

The aim of this work is to develop and test a lumped parameter model of the cardiovascular system to simulate the simultaneous use of pulsatile (P) and continuous flow (C) ventricular assist devices (VADs) on the same patient. Echocardiographic and hemodynamic data of five pediatric patients undergoing VAD implantation were retrospectively collected and used to simulate the patients' baseline condition with the numerical model. Once the baseline hemodynamic was reproduced for each patient, the following assistance modalities were simulated: (a) CVAD assisting the right ventricle and PVAD assisting the left ventricle (RCF + LPF), (b) CVAD assisting the left ventricle and PVAD assisting the right ventricle (LCF + RPF). The numerical model can well reproduce patients' baseline. The cardiac output increases in both assisted configurations (RCF + LPF: +17%, LCF + RPF: +21%, P = ns), left (right) ventricular volumes decrease more evidently in the configuration LCF + RPF (RCF + LPF), left (right) atrial pressure decreases in the LCF + RPF (RCF + LPF) modality. The pulmonary arterial pressure slightly decreases in the configuration LCF + RPF and it increases with RCF + LPF. Left and right ventricular external work increases in both configurations probably because of the total cardiac output increment. However, left and right artero-ventricular coupling improves especially in the LCF + RPF (-36% for the left ventricle and -21% for the right ventricle, P = ns). The pulsatility index decreases by 8.5% in the configuration LCF + RPF and increases by 6.4% with RCF + LPF (P = 0.0001). A numerical model could be useful to tailor on patients the choice of the VAD that could be implanted to improve the hemodynamic benefits. Moreover, a model could permit to simulate extreme physiological conditions and innovative configurations, as the implantation of both CVAD and PVAD on the same patient.

Use of Ventricular Assist Device in Univentricular Physiology: The Role of Lumped Parameter Models.

Failing single-ventricle (SV) patients might benefit from ventricular assist devices (VADs) as a bridge to heart transplantation. Considering the complex physiopathology of SV patients and the lack of established experience, the aim of this work was to realize and test a lumped parameter model of the cardiovascular system, able to simulate SV hemodynamics and VAD implantation effects. Data of 30 SV patients (10 Norwood, 10 Glenn, and 10 Fontan) were retrospectively collected and used to simulate patients' baseline. Then, the effects of VAD implantation were simulated. Additionally, both the effects of ventricular assistance and cavopulmonary assistance were simulated in different pathologic conditions on Fontan patients, including systolic dysfunction, diastolic dysfunction, and pulmonary vascular resistance increment. The model can reproduce patients' baseline well. Simulation results suggest that the implantation of VAD: (i) increases the cardiac output (CO) in all the three palliation conditions (Norwood 77.2%, Glenn 38.6%, and Fontan 17.2%); (ii) decreases the SV external work (SVEW) (Norwood 55%, Glenn 35.6%, and Fontan 41%); (iii) increases the mean pulmonary arterial pressure (Pap) (Norwood 39.7%, Glenn 12.1%, and Fontan 3%). In Fontan circulation, with systolic dysfunction, the left VAD (LVAD) increases CO (35%), while the right VAD (RVAD) determines a decrement of inferior vena cava pressure (Pvci) (39%) with 34% increment of CO. With diastolic dysfunction, the LVAD increases CO (42%) and the RVAD decreases the Pvci. With pulmonary vascular resistance increment, the RVAD allows the highest CO (50%) increment with the highest decrement of Pvci (53%). The single ventricular external work (SVEW) increases (decreases) increasing the VAD speed in cavopulmonary (ventricular) assistance. Numeric models could be helpful in this challenging and innovative field to support patients and VAD selection to optimize the clinical outcome and personalize the therapy.

The use of a numerical model to simulate the cavo-pulmonary assistance in Fontan circulation: a preliminary verification.

The lack of an established experience on the use of VAD for the cavo-pulmonary assistance leads to the need of dedicated VADs development and animal experiments. A dedicated numerical model could support clinical and experimental strategies design and new VADs testing. The aim of this work is to perform a preliminary verification of a lumped parameter model of the cardiovascular system to simulate Fontan physiology and the effect of cavo-pulmonary assistance. Literature data of 4 pigs were used to simulate animals' baseline, and then the model was tested in simulating Fontan circulation and cavo-pulmonary-assisted condition comparing the simulation outcome (Sim) with measured literature data (Me). The results show that the numerical model can well reproduce experimental data in all three conditions (baseline, Fontan and assisted Fontan) [cardiac output (l/min): Me = 2.8 ± 1.7, Sim = 2.8 ± 1.8; ejection fraction (%): Me = 57 ± 17, Sim = 54 ± 17; arterial systemic pressure (mmHg): Me = 41.8 ± 18.6, Sim = 43.8 ± 18.1; pulmonary arterial pressure (mmHg): Me = 15.4 ± 8.9, Sim = 17.7 ± 9.9; caval pressure (mmHg): Me = 6.8 ± 4.1, Sim = 7 ± 4.6]. Systolic elastance, arterial systemic and arterial pulmonary resistances increase (10, 69, and 100 %) passing from the biventricular circulation to the Fontan physiology and then decrease (21, 39, and 50 %) once the VAD was implanted. The ventricular external work decreases (71 %) passing from the biventricular circulation to the Fontan physiology and it increases three times after the VAD implantation in parallel with the VAD power consumption. A numerical model could support clinicians in an innovative and challenging field as the use of VAD to assist the Fontan physiology and it could be helpful to personalize the VAD insertion on the base of ventricular systo-diastolic function, circulatory parameters and energetic variables.

Osteogenic properties of a short BMP-2 chimera peptide.

Bone morphogenetic proteins (BMPs) play a key role in bone and cartilage formation. For these properties, BMPs are employed in the field of tissue engineering to induce bone regeneration in damaged tissues. To overcome drawbacks due to the use of entire proteins, synthetic peptides derived from their parent BMPs have come out as promising molecules for biomaterial design. On the structural ground of the experimental BMP-2 receptor complexes reported in the literature, we designed three peptides, reproducing the BMP-2 region responsible for the binding to the type II receptor, ActRIIB. These peptides were characterized by NMR, and the structural features of the peptide-receptor binding interface were highlighted by docking experiments. Peptide-receptor binding affinities were analyzed by means of ELISA and surface plasmon resonance techniques. Furthermore, cellular assays were performed to assess their osteoinductive properties. A chimera peptide, obtained by combining the sequence portions 73-92 and 30-34 of BMP-2, shows the best affinity for ActRIIB in the series and represents a good starting point for the design of new compounds able to reproduce osteogenic properties of the parent BMP-2.

Simulation of Ventricular, Cavo-Pulmonary, and Biventricular Ventricular Assist Devices in Failing Fontan.

Considering the lack of donors, ventricular assist devices (VADs) could be an alternative to heart transplantation for failing Fontan patients, in spite of the lack of experience and the complex anatomy and physiopathology of these patients. Considering the high number of variables that play an important role such as type of Fontan failure, type of VAD connection, and setting (right VAD [RVAD], left VAD [LVAD], or biventricular VAD [BIVAD]), a numerical model could be useful to support clinical decisions. The aim of this article is to develop and test a lumped parameter model of the cardiovascular system simulating and comparing the VAD effects on failing Fontan. Hemodynamic and echocardiographic data of 10 Fontan patients were used to simulate the baseline patients' condition using a dedicated lumped parameter model. Starting from the simulated baseline and for each patient, a systolic dysfunction, a diastolic dysfunction, and an increment of the pulmonary vascular resistance were simulated. Then, for each patient and for each pathology, the RVAD, LVAD, and BIVAD implantations were simulated. The model can reproduce patients' baseline well. In the case of systolic dysfunction, the LVAD unloads the single ventricle and increases the cardiac output (CO) (35%) and the arterial systemic pressure (Pas) (25%). With RVAD, a decrement of inferior vena cava pressure (Pvci) (39%) was observed with 34% increment of CO, but an increment of the single ventricle external work (SVEW). With the BIVAD, an increment of Pas (29%) and CO (37%) was observed. In the case of diastolic dysfunction, the LVAD increases CO (42%) and the RVAD decreases the Pvci, while both increase the SVEW. In the case of pulmonary vascular resistance increment, the highest CO (50%) and Pas (28%) increment is obtained with an RVAD with the highest decrement of Pvci (53%) and an increment of the SVEW but with the lowest VAD power consumption. The use of numerical models could be helpful in this innovative field to evaluate the effect of VAD implantation on Fontan patients to support patient and VAD type selection personalizing the assistance.

Ascending aortic extension to increase aortopulmonary space after comprehensive stage II palliation.

Aortic reconstruction at the time of the comprehensive stage II (CSII) procedure can be complicated by compression within the aortopulmonary space resulting in airway or pulmonary artery narrowing. We describe our experience with 2 patients with hypoplastic left heart syndrome and pulmonary artery stenosis after the CSII procedure. Both patients underwent an aortic extension with a Hemashield interposition graft to open up the aortopulmonary space. The patients were discharged from the hospital. In all cases the aortopulmonary space was enlarged, and the pulmonary arteries and airway were free from compression. Aortic extension is an option to be considered in children with pulmonary artery compression who previously had a CSII procedure.

Predictors of survival in paediatric mitral valve surgery: the impact of age at operation at late follow-up.

OBJECTIVES: The aim of this study was to elucidate predictors of death and reintervention after mitral valve (MV) surgery in children. METHODS: A single-centre retrospective study was performed enrolling 142 patients younger than 18 years who underwent primary index surgical mitral repair or replacement at Bambino Gesù Children's Hospital in Rome from July 1982 to April 2020. Patients with complete, transitional or partial atrioventricular septal defect and patients with single ventricle physiology were excluded. Patients were stratified according to the age group: group 1 (<1 year old), group 2 (1-5 years old) and group 3 (>5 years old). The composite primary outcome was freedom from death or transplant. The secondary outcome was freedom from redo MV surgery. RESULTS: Transplant-free survival was 89% at 5 years and 88% at 10 years. Stratified by age, group 1 had poorer outcome in comparison with other groups (log-rank test P = 0.105). Both univariate and multivariate analyses showed that age <1 year was a significant risk factor for death or transplant (P = 0.044). Age <1 year was associated with increased risk of reoperation (aHR = 3.38, P = 0.009), while the presence of genetic syndrome (aHR = 0.22) and preoperative EF% (aHR = 0.97) were protective factors for reoperation. CONCLUSIONS: The overall survival and freedom from reoperation in children undergoing MV surgery still need improvements. Younger age was a significant risk factor for death and reintervention both after repair and replacement of the MV. In particular, infants and neonates have a three-fold risk for death compared to children.

Predictors of survival in paediatric mitral valve replacement.

OBJECTIVES: The aim of this study was to identify the predictors of death and of reintervention after mitral valve replacement (MVR) in children. METHODS: A single-centre retrospective study was performed including 115 patients under the age of 18 undergoing MVR between 1982 and 2019. For all patients, the ratio of prosthetic valve size (diameter in mm) to weight (kg) at surgery was calculated and long-term result was assessed. The primary outcome was freedom from mitral valve (MV) re-replacement. The composite secondary outcome was freedom from death or transplant. RESULTS: Fifty-four patients had a previous surgical attempt to MV repair. The median age at surgery was 5.5 years (interquartile range 1.21-9.87). Death/transplant-free survival was 77 ± 4% at 5 years and 72 ± 5% at 10 years. Univariate analysis showed a size/weight ratio higher than 2 and age <2 years as significant risk factors for death or transplant. Freedom from MV re-replacement at 5 and 10 years was 90 ± 3% and 72 ± 6%, respectively. Biological prosthesis implanted at first replacement (P = 0.007) and size/weight ratio higher than 2 (P = 0.048) were predictors of reoperation. Significant upsizing (P < 0.0001) of mitral prosthesis was observed at re-replacement. CONCLUSIONS: MVR is a viable strategy in children with unrepairable MV disease. Mortality can be predicted based on size/weight ratio and age <2 years. MV re-replacement can be performed with low morbidity and mortality and a larger-size prosthesis can often be placed at the time of redo.

Pneumatic pulsatile ventricular assist device as a bridge to heart transplantation in pediatric patients.

Despite the remarkable advances with the use of ventricular assist devices (VAD) in adults, pneumatic pulsatile support in children is still limited. We report on our experience in the pediatric population. A retrospective review of 17 consecutive children offered mechanical support with Berlin Heart as a bridge to heart transplant from February 2002 to April 2010 was conducted. The median patient age was 3.9 years (75 days to 13.3 years). The median patient weight was 14.1 kg (2.9-43kg). Before VAD implantation, all children were managed by multiple intravenous inotropes and mechanical ventilation (14) or extracorporeal membrane oxygenation (3). All patients had right ventricular dysfunction. Nine patients required biventricular mechanical support (BVAD), but in all other cases a single left ventricular assist device proved sufficient (47%). The median duration of VAD support was 47 days (1-168 days). The median pre-VAD pulmonary vascular resistance index (Rpi) was 5.7 WU/m(2) (3.5 to 14.4WU/m(2) ). Eleven patients (65%) were successfully bridged to heart transplantation after a median duration of mechanical support of 68 days (6-168 days). Six deaths occurred (35%), three for neurological complications, one for sepsis, and two others for device malfunctioning. Since 2007, the survival rate of our patients has increased from 43% to 80%, and the need for BVAD has decreased from 86% to 30%. In two patients with Rpi >10WU/m(2) , unresponsive to pulmonary vasodilatator therapy, Rpi dropped to 2.2 and 2WU/m(2) after 40 and 23 days of BVAD support, respectively. Seven patients (41%) required at least one pump change. Of 11 patients undergoing heart transplant, four developed an extremely elevated (>60%) panel reactive antibody by enzyme-linked immunosorbent assay, confirmed by Luminex. All of them experienced at least one acute episode of rejection in the first month after heart transplant, needing plasmapheresis. The survival rate after heart transplantation was 100% with a median follow-up of 25.4 months (6 days to 7.7 years). Mechanical support in children with end-stage heart failure is an effective strategy as a bridge to heart transplantation with a reasonable morbidity and mortality. BVAD support may offer an additional means to reverse extremely elevated pulmonary vascular resistance.