Changes in adiponectin system after ventricular assist device in pediatric heart failure.

Background: Ventricular assist device (VAD) implant represents a therapeutic option for pediatric patients with end-stage heart failure (HF). Heart unloading by VAD can modify several molecular pathways underlying cardiac function in HF. Among them, the potential role of microRNA (miRNAs) in response to VAD implant is emerging. This study was aimed at investigating in HF pediatric patients the effect of VAD-modified miRNAs on the adiponectin (ADPN) system, known to exert cardioprotective actions. Methods: ADPN was measured in plasma samples obtained from HF children, before and 1 month after VAD implant, and from healthy control children. miRNA profile and molecules belonging to ADPN system were determined in cardiac biopsies collected at the time of VAD implantation (pre-VAD) and at the moment of heart transplant (post-VAD). An in vitro study using HL-1 cell line was performed to verify the regulatory role of the VAD-modified miRNA on the ADPN system. Results: VAD implant did not affect circulating and cardiac levels of ADPN, but increased the cardiac mRNA expression of ADPN receptors, including AdipoR1, AdipoR2, and T-cad. AdipoR2 and T-cad were inversely related to the VAD-modified miRNA levels. The in vitro study confirmed the regulatory role of miR-1246 and miR-199b-5p on AdipoR2, and of miR-199b-5p on T-cad. Conclusions: These data suggest that VAD treatment could regulate the expression of the cardioprotective ADPN system by epigenetic mediators, suggesting that miRNAs have a potential role as therapeutic targets to improve cardiac function in HF pediatric patients.

Right ventricle-pulmonary artery coupling in repaired tetralogy of Fallot with pulmonary regurgitation: Clinical implications.

BACKGROUND: Right ventricle-pulmonary artery (RV-PA) coupling is a strong prognostic marker in several clinical settings, but few studies have focused on its role in repaired tetralogy of Fallot (rToF) with pulmonary regurgitation. AIM: To assess whether differences exist in RV-PA coupling, estimated by echocardiography, between patients with rToF and pulmonary regurgitation with or without an indication for pulmonary valve replacement (PVR). METHODS: The study population included 40 patients with rToF, who were allocated to two groups: 20 with an indication for PVR (i-PVR group); and 20 without an indication for PVR (ni-PVR group). Forty healthy controls were also included. All subjects underwent echocardiography, and cardiac magnetic resonance (CMR) was available in 27/40 patients with rToF. RV-PA coupling was assessed by echocardiographic tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) and right ventricular stroke volume/right ventricular end-systolic volume (RVSV/RVESV) by CMR. RESULTS: TAPSE was similar in the i-PVR and ni-PVR groups (19.0±3.4 vs 18.8±2.7mm; P=0.97) whereas RV-PA coupling was significantly worse in the i-PVR group versus the ni-PVR group (TAPSE/PASP 0.8±0.3 vs 1.1±0.5mm/mmHg; P=0.001), and in the i-PVR group versus the control group (P=0.02); there was no difference between the ni-PVR and control groups (P=0.29). CMR data confirmed the echocardiography results, with a significant difference in RV-PA coupling between the i-PVR and ni-PVR groups (RVSV/RVESV 0.9±0.2 vs 1.2±0.3mL/min/mL; P=0.01). CONCLUSIONS: This study demonstrates worse RV-PA coupling, despite normal RV systolic function, in patients with rToF with an indication for PVR. RV-PA coupling could be a sensitive marker of a progressive maladaptive RV response to long-standing volume overload in rToF before the onset of clinical symptoms and RV systolic dysfunction.

Concomitant pulmonary and neurological embolisation in a Down patient after SARS-CoV-2 vaccine: what is missing?

A 40-year-old Down patient without previous cardiological history was admitted to our institution for dyspnoea after COVID-19 vaccine. CT scan revealed a pulmonary thromboembolism. One week later, he developed neurological impairment and CT scan evidenced a left parietal ischaemic lesion. Concomitantly, he underwent echocardiography showing an atrioventricular septal defect typically associated to Down syndrome and never diagnosed earlier. The diagnosis of paradoxical embolisation was then supposed. Echocardiography also revealed a severe right heart section dilatation, with bidirectional shunt on the septal defects and systemic right heart pressure. Down patients affected by CHD are more prone to develop pulmonary vasculopathy than non-syndromic patients. In this case, the pulmonary vasculopathy was further exacerbated by the pulmonary embolism and by the late diagnosis of CHD. Finally, an appropriate timely diagnosis of atrioventricular septal defect could potentially avoid the neurological complication in this patient.

Early Right Heart Chambers Reverse Remodeling in Patients Operated in Adulthood for Congenital Lesions Associated with Right Heart Chambers Enlargement.

BACKGROUND: Progressive right heart chambers dilatation is frequent in the adult congenital heart disease (ACHD) population. We evaluated the immediate and mid-term response of right heart chambers to surgery performed in adulthood for lesions associated with right heart chambers enlargement. METHODS: Thirty-six adult patients with lesions associated with right heart chambers enlargement submitted to surgery were studied. We collected echocardiographic data of right ventricle (RV) mid-diameter, right atrial volume indexed, RV systolic pressure, and tricuspid annular plane systolic excursion (TAPSE) prior to surgery (T0), at 2 to 5 days (T1), and 3 to 6 months (T2) after surgery. RESULTS: At T1, we observed a significant decrease of RV mid-diameter (47.2 ± 8.4 vs. 39.6 ± 7.4 mm, P < .001), right atrial volume indexed (45.6 ± 26.6 vs. 27.2 ± 11 ml/m2, P < .001), and RV systolic pressure (39 ± 14.8 vs. 32.8 ± 11.3 mm Hg, P = .03). At T2, a further significant deviation in the rate of RV diameter (39.6 ± 7.4 vs. 34.5 ± 5.1 mm, P < .001), in RV systolic pressure (32.8 ± 11.3 vs. 25.3 ± 5 mm Hg, P = .03) and TAPSE (13.9 ± 3.2 vs. 15.8 ± 2.6 mm, P < .001) was observed. CONCLUSIONS: Positive right heart chambers remodeling occurs as early as in the immediate post-operative period in most ACHD patients operated for lesions associated with right heart chambers enlargement.

Epigenetic Regulation of Cardiac Troponin Genes in Pediatric Patients with Heart Failure Supported by Ventricular Assist Device.

Ventricular Assist Device (VAD) therapy is considered as a part of standard care for end-stage Heart Failure (HF) children unresponsive to medical management, but the potential role of miRNAs in response to VAD therapy on molecular pathways underlying LV remodeling and cardiac function in HF is unknown. The aims of this study were to evaluate the effects of VAD on miRNA expression profile in cardiac tissue obtained from HF children, to determine the putative miRNA targets by an in-silico analysis as well as to verify the changes of predicated miRNA target in the same cardiac samples. The regulatory role of selected miRNAs on predicted targets was evaluated by a dedicated in vitro study. miRNA profile was determined in cardiac samples obtained from 13 HF children [median: 29 months; 19 LVEF%; 9 Kg] by NGS before VAD implant (pre-VAD) and at the moment of heart transplant (Post-VAD). Only hsa-miR-199b-5p, hsa-miR-19a-3p, hsa-miR-1246 were differentially expressed at post-VAD when compared to pre-VAD, and validated by real-time PCR. Putative targets of the selected miRNAs were involved in regulation of sarcomere genes, such as cardiac troponin (cTns) complex. The expression levels of fetal ad adult isoforms of cTns resulted significantly higher after VAD in cardiac tissue of HF pediatric patients when compared with HF adults. An in vitro study confirmed a down-regulatory effect of hsa-miR-19a-3p on cTnC expression. The effect of VAD on sarcomere organization through cTn isoform expression may be epigenetically regulated, suggesting for miRNAs a potential role as therapeutic targets to improve heart function in HF pediatric patients.

Deciphering Genetic Variants of Warfarin Metabolism in Children With Ventricular Assist Devices.

Warfarin is prescribed in patients with ventricular assist devices (VADs). Dosage depends on several factors including the underlying genotype. These include polymorphisms of genes encoding cytochrome P450 enzymes, the main ones being CYP2C9, VKORC1, and CYP4F2. The objectives of this study were to evaluate the prevalence of CY2CP9 1*2*3*, VKORC1, and CYP4F2 in children with VADs and the time to reach the target international normalized ratio. We performed a retrospective/prospective study in children with VADs. We recorded polymorphisms, disease, type of VAD, ethnicity, age, gender, height, weight, INR values, bleeding, and thromboembolic episodes. Informed consent was obtained. We enrolled 34 children (19 male, 15 female), with a median age of 2 years (range 0.3-17 years) and median weight of 6.9Kg. The Berlin Heart was the most commonly implanted VAD (22/34; 64%), and the most common diagnosis was dilated cardiomyopathy. Statistical analysis confirmed a significant partial correlation with VKORC1 CC (p = 0.019). The CYP2C9*2 CT genotype showed a late rise in target INR values (p = 0.06), while the CYP2C9*2 CC showed a tendency toward an early INR rise (p = 0.024). We provide new information on the contribution of the warfarin polymorphisms in children with VAD implantation. Pharmacogenomic dosing for children using warfarin has the potential to improve clinical care in VAD patients. Patients with the CYP2C9*2 CT genotype may need more time or higher doses to reach target INR, while clinicians may need to be aware of the potential for a rapid rise in INR in patients with the CYP2C9*2 CC genotype.

Telemedicine for adult congenital heart disease patients during the first wave of COVID-19 era: a single center experience.

AIM: To summarize our experience on the implementation of a telemedicine service dedicated to adult congenital heart disease (ACHD) patients during the lockdown for the first wave of Coronavirus disease 2019 (COVID-19). METHODS: This is a prospective study enrolling all ACHD patients who answered a questionnaire dedicated telematic cardiovascular examination. RESULTS: A total of 289 patients were enrolled, 133 (47%) were male, 25 (9%) were affected by a genetic syndrome. The median age was 38 (29-51) years, whereas the median time interval between the last visit and the telematic follow-up was 9.5 (7.5-11.5) months. Overall, 35 patients (12%) reported a worsening of fatigue in daily life activity, 17 (6%) experienced chest pain, 42 (15%) had presyncope and 2 (1%) syncope; in addition, 28 patients (10%) presented peripheral edema and 14 (5%) were orthopneic. A total of 116 (40%) patients reported palpitations and 12 had at least one episode of atrial fibrillation and underwent successful electrical (8) or pharmacological (4) cardioversion. One patient was admitted to the emergency department for uncontrolled arterial hypertension, five for chest pain, and one for heart failure. Two patients presented fever but both had negative COVID-19 nasal swab. CONCLUSION: During the COVID-19 pandemic, the use of telemedicine dramatically increased and here we report a positive experience in ACHD patients. The postpandemic role of telemedicine will depend on permanent regulatory solutions and this early study might encourage a more systematic telematic approach for ACHD patients.

Designing an Active Valvulated Outflow Conduit for a Continuous-Flow Left Ventricular Assist Device to Increase Pulsatility: A Simulation Study.

The purpose of this work was to investigate, using a lumped parameter model, the feasibility of increasing the pulsatility of a continuous-flow ventricular assist device (VAD) by implanting an active valvulated outflow cannula. A lumped parameter model was adopted for this study. VAD was modeled, starting from its pressure-flow characteristics. The valvulated outflow conduit was modeled as an active resistance described by a square function. Starting from pathologic condition, the following simulations were performed: VAD, VAD and valvulated outflow conduit in copulsation and counterpulsation with different ratios between the VAD valve opening rate and the heart rate, and asynchrony work with the heart with different VAD valve opening intervals. The copulsation 1:1 configuration and the asynchrony 0.3s-close-0.7s-open configurations permit to maximize the hemodynamic benefits provided by the presence of the active VAD outflow valvulated conduit providing an increase of arterial pulsatility from 1.86% to 14.98% without the presence of left ventricular output. The presence of the active VAD valve in the outflow conduit causes a decrement of the left ventricular unloading and of VAD flow and, that can be counteracted by increasing the VAD speed without affecting arterial pulsatility. The valvulated outflow tube provides an increase in arterial pulsatility; it can be driven in different working modality and can be potentially applicable to all types of VADs. However, the valvulated outflow conduit causes a decrement of left ventricular unloading and of the VAD flow that can be counteracted, increasing the VAD speed.

Increasing the pulsatility of continuos flow VAD: comparison between a valvulated outflow cannula and speed modulation by simulation.

To investigate by a lumped parameter model the feasibility of increasing the pulsatility of a continuous flow VAD, implanting an active valvulated outflow cannula and to compare the results with the haemodynamic outcome given by speed modulation methods. The concomitant presence of speed modulation and the active valvulated outflow conduit is also simulated. A lumped parameter model was adopted. VAD was modeled starting from its pressure flow characteristics with a second order polynomial equation. The valvulated outflow conduit was modeled as an active resistance described by a square function. Starting from pathological condition we simulated: VAD; VAD and valvulated outflow conduit in copulsation, counterpulsation and asynchrony work with the heart; VAD and active valvulated outflow tube and speed modulation. Copulsation 1:1 and asynchrony 0.3 s valve close-0.7 s valve open configurations maximised the haemodynamic benefits with the highest increment in pulsatility. The valvulated outflow conduit causes a decrement of the left ventricular unloading and of VAD flow that can be counteracted by increasing the VAD speed without affecting pulsatility. The concomitant use of the speed modulation and the active valvulated outflow conduit can further increase the pulsatility without altering left ventricular unloading and VAD flow. The valvulated outflow tube provide similar increase in pulsatility to speed modulation method but causes a decrement of left ventricular unloading and VAD flow that can be counteracted increasing the VAD speed or allowing a partial support. A valvulated outflow tube can be potentially applied to all continuous flow VADs.

Persistent myocardial atrophy despite LV reverse remodeling in Duchenne cardiomyopathy treated by LVAD.

DCM is the leading cause of death in Duchenne patients. LVADs are considered as therapeutic options as DT in advanced HF. The aim of our study was to evaluate LV remodeling of Duchenne after LVADs and chronic therapy. Demographic and echocardiographic data of 8 Duchenne patients implanted with LVADs were reviewed and analyzed. All measures were collected before LVAD implantation, after 1 month and 1 year. All patients were affected by end-stage DCM, and mean age at implantation was 16.9 ± 2.9 years. Patients were treated with maximal medical therapy. One-year post-implantation HR decreased from a mean of 110 ± 19 bpm to 82 ± 2 bpm (P = .002), and a significant decrease in LV volumes and diameters LVEDD P = .03, LVESD P = .02, EDV P = .01, and ESV P = .02) was noticed together with a significant increase in EF (P = .0036). However, RWT did not change over time, showing an eccentric remodeling pattern pre- and post-LVADs. Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of LV function secondary to a significant ventricular unloading due to LVADs coupled with chronic therapy.

Pathophysiology and molecular signalling in pediatric heart failure and VAD therapy.

Heart Failure (HF) is a progressive clinical syndrome characterized by molecular and structural abnormalities that result in impaired ventricular filling and a reduced blood ejection. In pediatric patients, HF represents an important cause of morbidity and mortality, but underlying cause, presentation and disease course remains unclear in many cases. It is evident that a child is not a "small adult" and findings are not comparable. The adoption of a standardized clinical and surgical tools as well as increased biomolecular research and therapeutic trials targeting pediatric patients with HF would greatly improve the management of this special class of patients. This review examines the most current information about the pathophysiology and molecular mechanisms related to HF in children to identify gaps in our knowledge base to further improve clinical care and outcomes.

Variations of circulating miRNA in paediatric patients with Heart Failure supported with Ventricular Assist Device: a pilot study.

Circulating miRNAs (c-miRNAs) are promising biomarkers for HF diagnosis and prognosis. There are no studies on HF pediatric patients undergoing VAD-implantation. Aims of this study were: to examine the c-miRNAs profile in HF children; to evaluate the effects of VAD on c-miRNAs levels; to in vitro validate putative c-miRNA targets. c-miRNA profile was determined in serum of HF children by NGS before and one month after VAD-implant. The c-miRNA differentially expressed were analyzed by real time-PCR, before and at 4 hrs,1,3,7,14,30 days after VAD-implant. A miRNA mimic transfection study in HepG2 cells was performed to validate putative miRNA targets selected through miRWalk database. Thirteen c-miRNAs were modified at 30 days after VAD-implant compared to pre-VAD at NSG, and, among them, six c-miRNAs were confirmed by Real-TimePCR. Putative targets of the validated c-miRNAs are involved in the hemostatic process. The in vitro study confirmed a down-regulatory effect of hsa-miR-409-3p towards coagulation factor 7 (F7) and F2. Of note, all patients had thrombotic events requiring pump change. In conclusion, in HF children, the level of six c-miRNAs involved in the regulation of hemostatic events changed after 30 days of VAD-treatment. In particular, the lowering of c-miR-409-3p regulating both F7 and F2 could reflect a pro-thrombotic state after VAD-implant.

Left ventricular unloading during extracorporeal membrane oxygenation - Impella versus atrial septal defect: A simulation study.

BACKGROUND: Atrial septal defect and Impella have been proposed for left ventricular unloading in venoarterial extracorporeal membrane oxygenation patients. This work aims at evaluating the haemodynamic changes in venoarterial extracorporeal membrane oxygenation patients after Impella implantation or atrial septal defect realization by a simulation study. METHODS: A lumped parameter model of the cardiovascular system was adapted to this study. Atrial septal defect was modelled as a resistance between the two atria. Venoarterial extracorporeal membrane oxygenation and Impella were modelled starting from their pressure-flow characteristics. The baseline condition of a patient undergoing venoarterial extracorporeal membrane oxygenation was reproduced starting from haemodynamic and echocardiographic data. The effects of different atrial septal defect size, Impella and venoarterial extracorporeal membrane oxygenation support were simulated. RESULTS: Impella caused an increment of mean arterial pressure up to 67%, a decrement in mean pulmonary arterial pressure up to 8%, a decrement in left ventricular end systolic volume up to 11% with a reduction up to 97% of left ventricular cardiac output. Atrial septal defect reduces left atrial pressure (19%), increases right atrial pressure (22%), increases mean arterial pressure (18%), decreases left ventricular end systolic volume (11%), increases right ventricular volume (33%) and decreases left ventricular cardiac output (55%). CONCLUSION: Impella has a higher capability in left ventricular unloading during venoarterial extracorporeal membrane oxygenation in comparison to atrial septal defect with a lower right ventricular overload.

Effects of levosimendan on ventriculo-arterial coupling and cardiac efficiency in paediatric patients with single-ventricle physiology after surgical palliation: retrospective study.

OBJECTIVES: The use of levosimendan for paediatric patients with low cardiac output after congenital heart surgery has been recently described. We sought to evaluate ventriculo-arterial coupling (VAC) and other ventricular energetic parameters before and after 72 h from levosimendan start in infants with single-ventricle physiology and cardiac failure after palliation with Norwood or hybrid procedures. METHODS: In this single-centre retrospective study, 9 consecutive patients affected by hypoplastic left heart syndrome-like anatomy were retrospectively analysed. Systolic elastance, diastolic elastance, arterial elastance, VAC and cardiac mechanical efficiency were calculated by measuring, through 2-dimensional echocardiography, end-systolic volume and end-diastolic volume and by recording mean arterial pressure and central venous pressure. RESULTS: The median (range) weight and age were 2.8 (2.3-6) kg and 16.5 (6-116) days, respectively. After 72 h from levosimendan start, end-systolic volume significantly decreased (-1 ml, -3.2 to -0.1, P = 0.007), whereas mean arterial pressure and end-diastolic volume remained stable. Heart rate showed a significant decrease (-28 beats/min, -41 to 22, P = 0.008). Systolic elastance (2.9 mmHg/ml, 0.4-5.4, P = 0.008), arterial elastance (-5.9, -24 to -0.5, P = 0.038), VAC (-0.86, -1.5 to -0.16, P = 0.009) and cardiac mechanical efficiency (0.18, 0.03-0.22, P = 0.008) differences also showed significant modifications. CONCLUSIONS: In a small case series of patients with single-ventricle physiology, levosimendan showed to improve contractility and optimize VAC, with a reduction of heart rate. Monitoring of VAC and ventricular energetics can be an interesting aspect to improve the management of heart failure in infants with univentricular anatomy.

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.

Changes in left and right ventricular two-dimensional echocardiographic speckle-tracking indices in pediatric LVAD population: A retrospective clinical study.

Echocardiographic strain and strain-rate imaging is a promising tool for the evaluation of myocardial segmental function, for the early detection of myocardial dysfunction, and for the prediction of reverse remodeling. We aimed at studying the changes in left and right ventricular function in pulsatile left ventricular assist device pediatric patients by two-dimensional echocardiography and two-dimensional speckle-tracking echocardiography. Echocardiographic and clinical data of patients implanted with a pulsatile-flow left ventricular assist device from 2011 to 2018 were retrospectively reviewed before and after implantation at 1, 3, and 6 months. A total of 18 patients were enrolled. Median age and weight at implantation were 9 months (5-23 months) and 5.85 kg (4.85-8.75 kg), respectively; median left ventricular assist device support was 181 (114.5-289.5) days. 13 patients (73%) were transplanted and 5 patients (27%) died. At follow-up: left ventricular ejection fraction increase at 1 month (p = 0.001) and 3 months (p = 0.01), left ventricular global longitudinal strain improvement at 1 month (p = 0.0008) and 3 months (p = 0.02), and right ventricular free-wall longitudinal strain increase at 1 month (p = 0.01). At short term after left ventricular assist device implantation, both left ventricular and right ventricular mechanics improved. The temporary benefit seems to decrease over time. The worsening of left ventricular function has been followed by a worsening of right ventricular function probably due to the ventricular interdependence.

The "Heart Valve Clinic" Pathway for the Management of Frail Patients With Valvular Heart Disease: From "One for All" to "All for One".

Valvular heart disease (VHD) is frequently diagnosed in old patients with clinical evidence of heart failure. This elderly population typically presents a high prevalence of frailty and comorbidities, which are associated with increased operative risk for surgical and percutaneous procedures. Recently, the Euro Heart Survey reported a clear gap between treatment guidelines and their application in the "real world". A more realistic approach to the treatment of older VHD patients treatment, mostly if associated with heart failure, is advocated. A multidisciplinary approach, as obtained with the Heart Valve Clinic methodology (intended to put the patient in the "center" of the scene and the specialists "around him"), has been applied in a group of 79 patients, aged >70 years, with symptomatic VHD, divided in 2 groups according to their frailty status (58 robust and 21 frail). No in-hospital mortality and no difference in late mortality and complications were observed. Infections were more frequent (14.3 vs. 1.7 %; P = 0.02) in frail patients. In patients with postoperative complications, serum levels of interleukin 6 (67.6 vs. 49.6; P = 0.01) and of CAF (C-terminal agrin fragment) as sarcopenia marker (67.9 vs. 62.0; P = 0.04) were higher than that in uncomplicated patients. This study was designed to determine the outcomes of the multidimensional geriatric assessment in the management of older patients with heart failure eligible for heart valve surgery. Geriatric assessment and measurement of inflammatory and sarcopenia markers may represent valid tools for a more realistic evaluation of elderly patients with VHD.

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.

Time-course of circulating cardiac and inflammatory biomarkers after Ventricular Assist Device implantation: Comparison between paediatric and adult patients.

BACKGROUND: Ventricular Assist Device (VAD) as bridge to transplantation is a common therapy for adult with heart failure (HF), but VAD use is increasing also in children. Cardiac and inflammatory biomarkers have an important role in the diagnosis and prognosis of HF in adults, but their role in paediatric setting is unknown. The aim of this study was to examine changes in cardiac and inflammatory biomarkers, both in HF paediatric and adult patients, before and following VAD. METHODS: Cardiac (NT-proBNP, cTnI, sST2,Gal-3) and inflammatory (IL-6,IL-8) biomarkers were determined in plasma collected from 12 paediatric patients and 7 adult patients with HF, before and at 4 h,1,3,7,14 and 30 days after VAD implant. RESULTS: All biomarkers increased up to 1 day after VAD implant and then decreased at pre-VAD levels in 1 month in both groups. Only in children, NT-proBNP decreased significantly after 30 days Post-VAD treatment compared to pre-VAD levels. During the post-operative time-course, NT-proBNP and sST2 were significantly higher in children than adults, while IL-6 was lower. CONCLUSIONS: Cardiac and inflammatory biomarkers were differently modified by VAD implant in children compared to adults. These preliminary data could suggest that different molecular pathways may underlie HF patho-physiology of the two groups, possibly paving the way to a specific and targeted therapeutic intervention in the near future.