Predictors and Impact of Prolonged Vasoplegia After Continuous-Flow Left Ventricular Assist Device Implantation.

Background: Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after continuous-flow left ventricular assist device (CF-LVAD) implantation are less known. Objectives: This study aimed to identify predictors of and outcomes from transient vs prolonged vasoplegia after CF-LVAD implantation. Methods: The study was a retrospective review of consecutive patients who underwent CF-LVAD implantation between January 1, 2005, and December 31, 2017. Vasoplegia was defined as the presence of all of the following: mean arterial pressure ≤65 mm Hg, vasopressor (epinephrine, norepinephrine, vasopressin, or dopamine) use for >6 hours within the first 24 hours postoperatively, cardiac index ≥2.2 L/min/m2 and systemic vascular resistance <800 dyne/s/cm5, and vasodilatory shock not attributable to other causes. Prolonged vasoplegia was defined as that lasting 12 to 24 hours; transient vasoplegia was that lasting 6 to <12 hours. Patient characteristics, outcomes, and risk factors were analyzed. Results: Of the 600 patients who underwent CF-LVAD implantation during the study period, 182 (30.3%) developed vasoplegia. Mean patient age was similar between the vasoplegia and no-vasoplegia groups. Prolonged vasoplegia (n = 78; 13.0%), compared with transient vasoplegia (n = 104; 17.3%), was associated with greater 30-day mortality (16.7% vs 5.8%; P = 0.02). Risk factors for prolonged vasoplegia included preoperative dialysis and elevated body mass index. Conclusions: Compared with vasoplegia overall, prolonged vasoplegia was associated with worse survival after CF-LVAD implantation. Treatment to avoid or minimize progression to prolonged vasoplegia may be warranted.

Personalized Numerical Cardiovascular Model with Weight Growth for Evaluating Pediatric Left Ventricular Assist Devices: Derivation from an Experimental Mock Circulatory Loop.

Pediatric patients with heart failure have limited treatment options because of a shortage of donor hearts and compatible left ventricular assist devices (LVADs). To address this issue, our group is developing an implantable pediatric LVAD for patients weighing 5-20 kg, capable of accommodating different physiological hemodynamic conditions as patients grow. To evaluate LVAD prototypes across a wide range of conditions, we developed a numerical cardiovascular model, using data from a mock circulatory loop (MCL) and patient-specific elastance functions. The numerical MCL was validated against experimental MCL results, showing good agreement, with differences ranging from 0 to 11%. The numerical model was also tested under left heart failure conditions and showed a worst-case difference of 16%. In an MCL study with a pediatric LVAD, a pediatric dataset was obtained from the experimental MCL and used to tune the numerical MCL. Then, the numerical model simulated LVAD flow by using an HQ curve obtained from the LVAD's impeller. When the numerical MCL was validated against the experimental MCL, hemodynamic differences ranged between 0 and 9%. These findings suggest that the numerical model can replicate various physiological conditions and impeller designs, indicating its potential as a tool for developing and optimizing pediatric LVADs.

Blood-contacting magnetic levitation bearing design using computational fluid dynamics for haemocompatibility.

The Hemocompatibility Assessment Platform (HAP) is a testing rig that will allow for the evaluation of blood trauma caused by individual components of rotary blood pumps including the NeoVAD - a proposed paediatric Left Ventricular Assist Device (LVAD). It is important that the HAP itself is only minimally haemolytic such that the plasma free haemoglobin measured can be assumed to come from the test component. In this study, Computational Fluid Dynamics simulations have been carried out to inform the design of a magnetically levitated motor bearing gap. Simulations show that issues with the original design, namely stagnation regions and large recirculation zones can be mitigated with the introduction of a pipe that introduces blood-flow to the centre of the bearing and disrupts the secondary flow patterns that cause these issues.Clinical relevance- The consequent reduction in shear exposure time will reduce heamolsyis from the HAP. The redesign of the bearing will result in reduced baseline blood trauma from the HAP, thus allowing quantification of test component haemolysis and will therefore aid the design of future paediatric LVADs.

A Two-Step Transcriptome Analysis of the Human Heart Reveals Broad and Disease-Responsive Expression of Ectopic Olfactory Receptors.

G-protein-coupled receptors (GPCRs) are critical regulators of cardiac physiology and a key therapeutic target for the treatment of heart disease. Ectopic olfactory receptors (ORs) are GPCRs expressed in extra-nasal tissues which have recently emerged as new mediators in the metabolic control of cardiac function. The goals of this study were to profile OR gene expression in the human heart, to identify ORs dysregulated by heart failure caused by ischemic cardiomyopathy, and to provide evidence suggestive of a role for those altered ORs in the pathogenesis of heart failure. Left ventricular tissue from heart failure patients (n = 18) and non-failing heart samples (n = 4) were subjected to a two-step transcriptome analysis consisting of the quantification of 372 distinct OR transcripts on real-time PCR arrays and simultaneous determination of global cardiac gene expression by RNA sequencing. This strategy led to the identification of >160 ORs expressed in the human heart, including 38 receptors differentially regulated with heart failure. Co-expression analyses predicted the involvement of dysregulated ORs in the alteration of mitochondrial function, extracellular matrix remodeling, and inflammation. We provide this dataset as a resource for investigating roles of ORs in the human heart, with the hope that it will assist in the identification of new therapeutic targets for the treatment of heart failure.

Machine learning based on computational fluid dynamics enables geometric design optimisation of the NeoVAD blades.

The NeoVAD is a proposed paediatric axial-flow Left Ventricular Assist Device (LVAD), small enough to be implanted in infants. The design of the impeller and diffuser blades is important for hydrodynamic performance and haemocompatibility of the pump. This study aimed to optimise the blades for pump efficiency using Computational Fluid Dynamics (CFD), machine learning and global optimisation. Meshing of each design typically included 6 million hexahedral elements and a Shear Stress Transport turbulence model was used to close the Reynolds Averaged Navier-Stokes equations. CFD models of 32 base geometries, operating at 8 flow rates between 0.5 and 4 L/min, were created to match experimental studies. These were validated by comparison of the pressure-flow and efficiency-flow curves with those experimentally measured for all base prototype pumps. A surrogate model was required to allow the optimisation routine to conduct an efficient search; a multi-linear regression, Gaussian Process Regression and a Bayesian Regularised Artificial Neural Network predicted the optimisation objective at design points not explicitly simulated. A Genetic Algorithm was used to search for an optimal design. The optimised design offered a 5.51% increase in efficiency at design point (a 20.9% performance increase) as compared to the best performing pump from the 32 base designs. An optimisation method for the blade design of LVADs has been shown to work for a single objective function and future work will consider multi-objective optimisation.

The Evolution of Durable, Implantable Axial-Flow Rotary Blood Pumps.

Left ventricular assist devices (LVADs) are increasingly used to treat patients with end-stage heart failure. Implantable LVADs were initially developed in the 1960s and 1970s. Because of technological constraints, early LVADs had limited durability (eg, membrane or valve failure) and poor biocompatibility (eg, driveline infections and high rates of hemolysis caused by high shear rates). As the technology has improved over the past 50 years, contemporary rotary LVADs have become smaller, more durable, and less likely to result in infection. A better understanding of hemodynamics and end-organ perfusion also has driven research into the enhanced functionality of rotary LVADs. This paper reviews from a historical perspective some of the most influential axial-flow rotary blood pumps to date, from benchtop conception to clinical implementation. The history of mechanical circulatory support devices includes improvements related to the mechanical, anatomical, and physiologic aspects of these devices. In addition, areas for further improvement are discussed, as are important future directions-such as the development of miniature and partial-support LVADs, which are less invasive because of their compact size. The ongoing development and optimization of these pumps may increase long-term LVAD use and promote early intervention in the treatment of patients with heart failure.

Continuous-Flow Ventricular Assist Device Support in Adult Congenital Heart Disease: A 15-Year, Multicenter Experience of Temporary and Durable Support.

Heart failure (HF) is common in adult congenital heart disease (ACHD) patients; however, use of continuous-flow ventricular assist devices (CF-VADs) remains rare. We reviewed outcomes of patients with congenital heart disease greater than or equal to 18 years of age at the time of CF-VAD implant at the affiliated pediatric and adult institutions between 2006 and 2020. In total, 18 ACHD patients (15 with great anatomical complexity) received 21 CF-VADs. Six patients (median age 34 years) received seven percutaneous CF-VADs with a median duration of support of 20 days (3-44 days) with all patients survived to hospital discharge and two patients were bridged to durable CF-VADs. Fourteen patients (median age 38 years) received durable CF-VADs. Thirteen patients (93%) survived to hospital discharge and the median duration of support was 25.8 months (6.4-52.1 months). Estimated survival on durable CF-VAD at 1, 3, and 5 years was 84%, 72%, and 36%, respectively. Three patients were successfully bridged to transplantation. Device-related complications include cerebrovascular accident (n = 5), driveline infection (n = 3), device infection requiring chronic antibiotic therapy (n = 4), gastrointestinal bleeding (n = 6), and presumed pump thrombosis (n = 5). These results show percutaneous and durable CF-VADs can support ACHD patients with advanced HF.

The Jarvik 2000 Left Ventricular Assist Device: Results of the United States Bridge to Transplant Trial.

The Jarvik 2000 bridge to transplant investigational device exemption study was a multicentered, prospective study of 150 UNOS status I patients implanted with the Jarvik 2000 between 2005 and 2012. During the study period, there were numerous modifications of the system that included converting from pin to cone bearings. Results were analyzed for three cohorts: total (n = 150), pin (n = 128), and cone (n = 22). Baseline demographics included age (52 ± 13), gender (79% male), size (BSA 1.98), and etiology (37% idiopathic dilated cardiomyopathy; 43% Ischemic). Seventy percent of patients were either INTERMACS 1 or 2. The primary endpoint-defined as successful transplantation or listing at 180 days (prespecified at 65%; 95% lower CI: 57%)-was successfully achieved for the total cohort (67.3%; 95% CI: 59.5%-74.3%; p = 0.006). In subgroup analysis of the more contemporary, cone-bearing group, the primary endpoint was met in 91% (95% CI: 72%-97.5%; p = 0.001). Compared with pin patients, cone-bearing patients had less hemolysis as well as decreased end-organ dysfunction. Functional and quality of life scores improved after implantation independent type of bearing. In conclusion, despite a particularly sick patient population, the Jarvik 2000 was shown to be effective in supporting the advanced HF patient.

Dynamic Evaluation of an Active Axial Magnetic Levitated Bearing System in a Hemocompatibility Assessment Platform.

To evaluate the hemocompatibility of individual components of our pediatric left ventricular assist device (LVAD), we proposed a hemocompatibility assessment platform (HAP) with a magnetic levitated bearing system. The HAP consists of a drive system utilizing a brushless direct current (BLDC) motor, passive magnetic bearings (PMB), and an active magnetically levitated bearing (AMB) to reduce the hemolysis generated by HAP itself. In this study, we designed and evaluated the performance of the AMB by measuring radial and axial displacements of the rotor resulting from radially destabilizing forces as well as the performance of the drive system when rotated at increasing speeds to 1,200 rotations per minute (rpm). The results show that, with radial disturbance, the AMB is capable of maintaining axial stability for the BLDC motor system. The AMB can control up to 1,200 rpm without any contact between the rotor and stator. Future work includes geometry optimization for the AMB structure and increase the capability to control stable high-speed rotation for the entire system. Clinical Relevance- This work furthers the development of the magnetic levitated bearing system for a hemocompatibility assessment platform that will be used to enhance and accelerate the development of adult and pediatric LVADs.

Numerical and Experimental Analysis for a Magnetic Levitation System in a Hemocompatibility Assessment Platform.

Development of pediatric left ventricular assist devices (LVADs) has lagged behind that of adult LVADs, primarily due to the size and hemocompatibility constraints of pediatric anatomy. To quantify sources of blood trauma during LVAD development, we proposed a hemocompatibility assessment platform (HAP) that can evaluate the hemocompatibility of individual components of LVADs. To eliminate the hemolysis induced by the HAP itself, we incorporated passive magnetic (PM) bearings to suspend the rotor radially and an active magnetic bearing (AMB) to control the axial position. In this study, we numerically evaluated AMB forces of 2 geometries and validated the model by comparing its predictions with experimental results. The magnetic forces generated by the AMB were evaluated by increasing the rotor-stator gap from 0.1 mm to 0.5 mm with a 0.1 mm increment and by varying the coil current from -2 A to 2 A with a 1 A increment. The average error of the numerical models was 8.8% and 7.0% for the two geometries, respectively. Higher errors were found at smaller (<0.2mm) rotor-stator gaps. For both biasing ring sizes, the AMB exhibits high magnetic stiffness from -1 A to 1 A, though it saturates for currents of -2 A and 2 A. This region of high current stiffness was identified as the optimal control region. In future work, this function will be used to tune a control algorithm to modulate current supplied to the AMB, ultimately stabilizing the rotor axially. Clinical Relevance- This work furthers the development of a hemocompatibility assessment platform that will enhance and accelerate the development of adult and pediatric LVADs.

Physiological Control Algorithm for a Pulsatile-flow 3D Printed Circulatory Model to Simulate Human Cardiovascular System.

The human heart is responsible for maintaining constant, pulsatile blood flow in the human body. Mock circulatory loops (MCLs) have long been used as the mechanical representations of the human cardiovascular system and as test beds for mechanical circulatory support (MCS) devices and other interventional medical devices. This technology could also be used as a training and educational tool for surgeons/clinicians. To ensure the MCL can accurately simulate the pulsatile human cardiovascular system, it is essential that the MCL can reproduce human physiological responses, e.g., the Frank-Starling Mechanism, in a controllable operating environment. In this study, by using an elastance function template to control the simulated left ventricle, we created controllable pulsatile physiological flow in a 3D printed silicone vascular structure to successfully simulate the hemodynamic environment of the human cardiovascular system. Clinical Relevance- This work will provide an in vitro test platform to simulate the human cardiovascular system. The accurate simulation of human cardiovascular anatomy and hemodynamic environment will allow this device to be an ideal training/educational tool for surgeons/clinicians to recreate various physiological conditions that cannot be created in vivo in animal or cadaver models.

The influence of preoperative dialysis on survival after continuous-flow left ventricular assist device implantation.

OBJECTIVES: Dialysis is considered a contraindication to continuous-flow left ventricular assist device (CF-LVAD) implantation. We evaluated clinical outcomes and survival in carefully selected, low-risk patients with renal failure who required dialysis before CF-LVAD implantation. METHODS: We extracted medical record data of patients who underwent CF-LVAD placement at our centre between 1 January 2006 and 31 August 2017, with 2 clinical scenarios: those who required long-term (>14 days) dialysis and those who required short-term (≤14 days) dialysis immediately before implantation. Demographic, clinical and intraoperative characteristics and survival outcomes were assessed. RESULTS: Of 621 patients who underwent CF-LVAD implantation during the study period, 31 underwent dialysis beforehand. Of these, 17 required long-term dialysis (13 haemodialysis, 4 peritoneal dialysis), and 14 underwent short-term haemodialysis. Compared with the long-term dialysis patients, the short-term dialysis patients were more likely to be Interagency Registry for Mechanically Assisted Circulatory Support profile 1-2 (92.9% vs 70.6%; P < 0.001), to have needed preoperative mechanical circulatory support (78.6% vs 70.6%; P < 0.01) and to have higher in-hospital mortality (85.7% vs 29.4%; P = 0.01). Patients stable on long-term dialysis had acceptable overall survival and markedly better 6-month and 1-year survival than those with short-term dialysis before implantation (64.7% vs 14.3% and 58.8% vs 7.1%, respectively; P < 0.001). CONCLUSIONS: Carefully selected patients who are stable on long-term dialysis have acceptable survival rates after CF-LVAD implantation. Patients with acute renal failure had much poorer outcomes than those with chronic end-stage renal disease.

Feasibility of long-term continuous flow total heart replacement in calves.

INTRODUCTION: Implementation of continuous flow (CF) technology in modern ventricular assist devices (VAD) has afforded a wealth of engineering and design advantages in the development of a total artificial heart (TAH). However, clinical application of CF has created a unique physiologic state, the consequences of which remain largely unknown. We sought to evaluate clinical and biochemical markers of end-organ function in calves supported with biventricular CF VADs for more than 30 days. METHODS: Eight calves survived longer than 30 days following biventriculectomy and implantation of dual CF VADs. Four types of CF pumps were utilized for the study. Serial hematologic and biochemical profiles were drawn as markers for end-organ function, and hemodynamic data-including pump flows and intravascular pressures-were continuously monitored. RESULTS: The eight calves survived an average of 58.8 days (range 30-92 days). Two of the calves were electively terminated at the conclusion of the study period, while the remaining animals were euthanized as a result of respiratory distress (n = 2) or impaired pump flows (n = 4). In each case, serial biochemical and hematologic values were suggestive of preserved end-organ function. Six animals successfully participated in treadmill exercise evaluations. No evidence of end-organ damage was encountered upon necropsy or histologic tissue analysis. CONCLUSION: Biventricular CF VAD implantation permits a viable bovine CFTAH model capable of demonstrating long-term survival. After 30 days of completely nonpulsatile flow, cumulative hemodynamic, clinical, biochemical, and histological analyses were consistent with preserved end-organ function, suggesting previously unreported long-term feasibility of a CFTAH design.

Hemocompatibility Assessment Platform Drive System Design: Trade-off between Motor Performance and Hemolysis.

Left ventricular assist devices (LVADs) have long been used to treat adults with heart failure, but LVAD options for pediatric patients with heart failure are lacking. Despite the urgent need for long-term, implantable pediatric LVADs, design challenges such as hemolysis, pump thrombosis, and bleeding persist. We have developed a Hemocompatibility Assessment Platform (HAP) to identify blood trauma from individual LVAD components. A HAP would aid in refining pump components before in vivo testing, thereby preventing unnecessary animal sacrifice and reducing development time and cost. So that the HAP does not confound hemolysis data, the HAP drive system consists of an enlarged air-gap motor coupled to a magnetic levitation system. Although it is known that an enlarged air gap motor will have diminished performance, while the larger gap in the motor will cause less blood damage, the trade-offs are not fully characterized. Therefore, in this study we evaluated these trade-offs to determine an optimal rotor diameter for the HAP drive motor. The motor performance was characterized with an experimental method by determining the torque constant for the HAP drive motor with varied rotor diameters. The torque threshold was set as 10 mNm to achieve a nominal current of 3.5A. Hemolysis in the HAP drive motor gap was estimated by calculating scalar shear stress generated in the HAP motor gap analytically and numerically. A design criterion of 30 Pa was selected for scalar shear stress to achieve minimal hemolysis and platelet activation in the HAP drive system.Clinical Relevance- We evaluated a Hemocompatibility Assessment Platform for developing LVAD prototypes that can best balance motor performance and hemocompatibility. This design method can assist with optimizing the drive system during the research stage and illustrates how motor geometry can be tuned to reduce blood trauma.

Preparing end-stage heart failure patients and care providers in the era of climate change-driven hurricanes.

Patients with end-stage congestive heart failure are at elevated risk for harm when extreme storms threaten and strike their communities. Individuals with compromised heart function require customized hurricane protection and preparedness approaches. We provide mitigation strategies for providers and their teams, as well as the patients themselves to ensure their safety and uninterrupted access to healthcare resources and quality care during hurricane impact and in the aftermath.

Continuous-Flow Left Ventricular Assist Device Explantation After More Than 5 Years of Circulatory Support and Ventricular Reconditioning.

Continuous-flow left ventricular assist devices have proved to be effective, durable, life-saving tools in patients with end-stage heart failure. However, because of the risks associated with mechanical circulatory support (including stroke, infection, gastrointestinal bleeding, and device malfunction), the optimal goal of device therapy is myocardial recovery and device removal. Ventricular reconditioning and pump explantation after continuous-flow support have been reported; however, little is known about variables that govern the pace and degree of myocardial response in patients who experience such recovery. We describe our long-term pump-weaning strategy for a 25-year-old man who had a continuous-flow device implanted and then needed more than 5 years of support from it before developing cardiac reserve sufficient to enable pump explantation. To our knowledge, this is the longest period of uninterrupted continuous-flow device support to end in successful pump deactivation and a return to medical therapy. This case highlights the importance of actively and persistently pursuing a device-weaning strategy in all patients who need left ventricular assist device therapy.

Continuous-Flow Left Ventricular Assist Device Therapy in Adults with Transposition of the Great Vessels.

An increasing number of children with congenital heart disease are surviving into adulthood and subsequently developing end-stage heart failure. Two example populations are adults who have been previously operated on for congenitally corrected transposition of the great arteries (CCTGA) and transposition of the great arteries (TGA). Implantation of a continuous flow left ventricular assist device (CF-LVAD) in these patients can present unusual anatomical and physiologic challenges. In this report, we describe outcomes of CF-LVAD implantation in three such patients. These cases demonstrate the feasibility of implanting a CF-LVAD in patients who have undergone surgery for CCTGA and/or TGA.

Numerical and Experimental Approach to Characterize a BLDC Motor with Different Radial-gap to Improve Hemocompatibility Performance.

Left ventricular assist devices (LVADs) have increasingly been used clinically to treat heart failure patients. However, hemolysis, pump thrombosis, infection and bleeding still persist as major limitations of LVAD technology. Assessing LVAD hemocompatibility using a blood shear stress device (BSSD) has clear advantages, as the BSSD could provide a better experimental platform to develop reliable, quantifiable blood trauma assays to perform iterative testing of LVAD designs. In this study, a BSSD was proposed with short blood exposure time and no seals or contact bearings to reduce blood trauma caused by the test platform. Enlarged air-gap drive motor in BSSD is essential to avoid high shear stress; however, it would significantly reduce the motor torque, which may result in inadequate force to drive the entire system. In order to evaluate and optimize the drive motor air-gap to ensure adequate motor torque as well as acceptable range for blood exposure time and shear stress, a numerical brushless DC (BLDC) motor model was established using finite element method (FEM) in numerical simulation software COMSOL. The model was first validated by the experimental results. Then numerical model with different air-gap was evaluated on the torque and speed constant changes. In the end, two equations were generated based on the curves derived from the torque and speed constant calculations. Determining these relationships between motor performance and motor air-gap will facilitate the development of an appropriate BLDC motor size for the BSSD, considering the design limitations in our future work.