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.

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.

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.

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.

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.

Control of a Pediatric Pulsatile Ventricular Assist Device: A Hybrid Cardiovascular Model Study.

The aim of this work is to study pediatric pneumatic ventricle (PVAD) performance, versus VAD rate (VADR) and native heart rate (HR) ratio Rr (VADR/HR). The study uses a hybrid model of the cardiovascular system (HCS). HCS consists of a computational part (a lumped parameter model including left and right ventricles, systemic and pulmonary arterial and venous circulation) interfaced to a physical part. This permits the connection of a VAD (15 mL PVAD). Echocardiographic and hemodynamic data of a pediatric patient (average weight 14.3 kg, HR 100 bpm, systemic pressure 75/44 mm Hg, CO 1.5 L/min) assisted apically with asynchronous PVAD were used to set up a basal condition in the model. After model tuning, the assistance was started, setting VAD parameters (ejection and filling pressures, systole duration) to completely fill and empty the PVAD. The study was conducted with constant HR and variable VADR (50-120, step 10, bpm). Experiments were repeated for two additional patients' HRs, 90 and 110 bpm and for two values of systemic arterial resistance (Ras ) and Emax . Experimental data were collected and stored on disk. Analyzed data include average left and right ventricular volumes (LVV, RVV), left ventricular flow (LVF), VAD flow (VADF), and total cardiac output (COt). Data were analyzed versus Rr. LVV and RVV are sensitive to Rr and a left ventricular unloading corresponds in general to a right ventricular loading. In the case of asynchronous assistance, frequency beats are always present and the beat rate is equal to the difference between HR and VADR. In the case of pulsatile asynchronous LVAD assistance, VADR should be chosen to minimize frequency beat effects and right ventricular loading and to maximize left ventricular unloading.

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.

Hemodynamic Effects of Ventricular Assist Device Implantation on Norwood, Glenn, and Fontan Circulation: A Simulation Study.

The growing population of failing single-ventricle (SV) patients might benefit from ventricular assist device (VAD) support as a bridge to heart transplantation. However, the documented experience is limited to isolated case reports. Considering the complex and different physiopathology of Norwood, Glenn, and Fontan patients and the lack of established experience, the aim of this work is to realize and test a lumped parameter model of the cardiovascular system able to simulate SV hemodynamics and VAD implantation effects to support clinical decision. Hemodynamic and echocardiographic 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. Simulation results suggest that the implantation of VAD: (i) increases the cardiac output and the mean arterial systemic pressure in all the three palliation conditions (Norwood 77.2 and 19.7%, Glenn 38.6 and 32.2%, and Fontan 17.2 and 14.2%); (ii) decreases the SV external work (Norwood 55%, Glenn 35.6%, and Fontan 41%); (iii) decreases the pressure pulsatility index (Norwood 65.2%, Glenn 81.3%, and Fontan 64.8%); (iv) increases the pulmonary arterial pressure in particular in the Norwood circulation (Norwood 39.7%, Glenn 12.1% and Fontan 3%); and (v) decreases the atrial pressure (Norwood 2%, Glenn 10.6%, and Fontan 8.6%). Finally, the VAD work is lower in the Norwood circulation (30.4 mL·mm Hg) in comparison with Fontan (40.3 mL·mm Hg) and to Glenn (64.5 mL·mm Hg) circulations. The use of VAD in SV physiology could be helpful to bridge patients to heart transplantations by increasing the CO and unloading the SV with a decrement of the atrial pressure and the SV external work. The regulation of the pulmonary flow is challenging because the Pap is increased by the presence of VAD. The hemodynamic changes are different in the different SV palliation step. The use of numerical models could be helpful to support patient and VAD selection to optimize the clinical outcome.

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.

The relationship between R-wave magnitude and ventricular volume during continuous left ventricular assist device assistance: experimental study.

The current use of left ventricular assist devices (LVADs) as destination therapy is associated with the clinical need of monitoring patient-pump interaction. To this aim, the present work investigated the possibility of getting useful information about the status of the assisted left ventricle using electrocardiographic (ECG) data. A total of six animals, undergoing Gyro Centrifugal Pump 2 implantation (a new version of Gyro Centrifugal Pump C1E3 [Kyocera Corporation, Kyoto, Japan]) and CircuLite Synergy Micropump (CircuLite, Inc., Saddlebrooke, NJ, USA) in atrio-aortic connection, were analyzed. Data refer to different LVAD speeds with consequently different levels of ventricular unloading. From ECG signal, the R wave peak was individuated together with the corresponding left ventricular volume. Then on both signals, a moving average analysis was performed to reduce the effect of the ventilation. A regression and correlation analysis performed on the two resulting signals evidenced that the R wave peak and the ventricular volume are strictly related. Specifically, any change of LVAD speed, inducing a change in ventricular volume, is associated with a change in R wave peak value. The present work is a first step in investigating the usefulness of the ECG signal during LVAD therapy, for the monitoring of mechanical parameters of the heart such as the ventricular volumes. The correlation found between the ECG and the ventricular volume can be a promising starting point for possible future noninvasive LVAD patient monitoring.

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.

Reproduction of continuous flow left ventricular assist device experimental data by means of a hybrid cardiovascular model with baroreflex control.

Long-term mechanical circulatory assistance opened new problems in ventricular assist device-patient interaction, especially in relation to autonomic controls. Modeling studies, based on adequate models, could be a feasible approach of investigation. The aim of this work is the exploitation of a hybrid (hydronumerical) cardiovascular simulator to reproduce and analyze in vivo experimental data acquired during a continuous flow left ventricular assistance. The hybrid cardiovascular simulator embeds three submodels: a computational cardiovascular submodel, a computational baroreflex submodel, and a hydronumerical interface submodel. The last one comprises two impedance transformers playing the role of physical interfaces able to provide a hydraulic connection with specific cardiovascular sites (in this article, the left atrium and the ascending/descending aorta). The impedance transformers are used to connect a continuous flow pump for partial left ventricular support (Synergy Micropump, CircuLite, Inc., Saddlebrooke, NJ, USA) to the hybrid cardiovascular simulator. Data collected from five animals in physiological, pathological, and assisted conditions were reproduced using the hybrid cardiovascular simulator. All parameters useful to characterize and tune the hybrid cardiovascular simulator to a specific hemodynamic condition were extracted from experimental data. Results show that the simulator is able to reproduce animal-specific hemodynamic status both in physiological and pathological conditions, to reproduce cardiovascular left ventricular assist device (LVAD) interaction and the progressive unloading of the left ventricle for different pump speeds, and to investigate the effects of the LVAD on baroreflex activity. Results in chronic heart failure conditions show that an increment of LVAD speed from 20 000 to 22 000 rpm provokes a decrement of left ventricular flow of 35% (from 2 to 1.3 L/min). Thanks to its flexibility and modular structure, the simulator is a platform potentially useful to test different assist devices, thus providing clinicians additional information about LVAD therapy strategy.

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.

Endothelial dysfunction is a marker of systemic response to the cardiac resynchronization therapy in heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) induces a significant improvement in patients with heart failure (HF), who are often characterized by the presence of endothelial dysfunction (ED) with impaired flow-mediated vasodilation (FMD). We aimed to study the ED in patients with HF candidates to CRT with defibrillator (CRT-D). METHODS AND RESULTS: We studied 57 consecutive patients affected by HF and undergoing CRT-D. At the baseline we recorded a high prevalence of ED (64.9%) with impaired FMD (4.1 ± 3.8%). After 12 months of CRT, we reported a marked increase of the mean FMD (8.8 ± 4.8% vs 4.1 ± 3.8%; P < .05) along with significant improvement of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) functional class, and 6-minute walk test (6MWT); 42 patients (73.7%) were classified as responders according to standard criteria. FMD was related to LVEF (r = 0.169; P < .05), LVESV (r = -0.169; P < .05), NYHA functional class (r = -0.27; P < .051), and 6MWT (r = 0.360; P < .01). CONCLUSIONS: ED is not an independent predictor of CRT response, but it is able to intercept the systemic effects of CRT and is an affordable marker of response to CRT, especially in patients unable to perform the 6MWT.

Effects of intra-aortic balloon pump timing on baroreflex activities in a closed-loop cardiovascular hybrid model.

Despite 50 years of research to assess the intra-aortic balloon pump (IABP) effects on patients' hemodynamics, some issues related to the effects of this therapy are still not fully understood. One of these issues is the effect of IABP, its inflation timing and duration on peripheral circulation autonomic controls. This work provides a systematic analysis of IABP effects on baroreflex using a cardiovascular hybrid model, which consists of computational and hydraulic submodels. The work also included a baroreflex computational model that was connected to a hydraulic model with a 40-cm(3) balloon. The IABP was operated at different inflation trigger timings (-0.14 to 0.31 s) and inflation durations (0.05-0.45 s), with time of the dicrotic notch being taken as t = 0. Baroreflex-dependent parameters-afferent and efferent pathway activity, heart rate, peripheral resistance, and venous tone-were evaluated at each of the inflation trigger times and durations considered. Balloon early inflation (0.09 s before the dicrotic notch) with inflation duration of 0.25 s generated a maximum net increment of afferent pathway activity of 10%, thus leading to a decrement of efferent sympathetic activity by 15.3% compared with baseline values. These times also resulted in a reduction in peripheral resistance and heart rate by 4 and 4.3% compared with baseline value. We conclude that optimum IABP triggering time results in positive effects on peripheral circulation autonomic controls. Conversely, if the balloon is not properly timed, peripheral resistance and heart rate may even increase, which could lead to detrimental outcomes.