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.

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.

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.

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.

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.

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.

Factor Xa inhibitors in patients with continuous-flow left ventricular assist devices.

OBJECTIVE: Warfarin is standard anticoagulation therapy for patients with a continuous-flow left ventricular assist device (CF-LVAD). However, warfarin requires regular monitoring and dosage adjustments and fails for many patients, causing thromboembolic and bleeding events. Factor Xa inhibitors have been shown to be noninferior to warfarin in preventing strokes and are associated with less intracranial hemorrhage in patients with atrial fibrillation. We evaluated treatment safety and effectiveness in CF-LVAD patients who switched from warfarin to a factor Xa inhibitor (apixaban or rivaroxaban) after warfarin failure. METHODS: This was a retrospective, single-center study of patients treated between 2008 and 2018. We assessed the occurrence of stroke, non-central nervous system (CNS) embolism, pump thrombosis, and major gastrointestinal bleeding and intracranial hemorrhage during therapy. RESULTS: We identified seven patients: five were male, the average body mass index was 30 kg/m2, and average age was 56 years. Preimplantation comorbidities included hypertension (all patients) and diabetes mellitus, ischemic cardiomyopathy, atrial fibrillation, and previous myocardial infarction (four patients each). Overall, patients received warfarin for 3968 days and apixaban/rivaroxaban for 1459 days. The warfarin group was within the therapeutic INR range (2.0-3.0) 30% of the time. Complication rates did not differ between warfarin and apixaban/rivaroxaban: strokes, 0.20 vs none, non-CNS embolism, 0.54 vs none; pump thrombosis, 0.27 vs none; major gastrointestinal bleeding, 0.20 vs 0.50; intracranial hemorrhage, 0.13 vs none. CONCLUSIONS: Factor Xa inhibitors may be viable treatment options for CF-LVAD patients for whom warfarin therapy has failed. Large prospective studies are necessary to confirm these results.

Heterotopic Cardiac Transplantation: Long-term Results and Fate of the Native Heart.

BACKGROUND: The long-term results of heterotopic cardiac transplantation have not been well defined. Patient survival rates and the fate of the native heart remain unclear. METHODS: This study is a retrospective review of all 46 heterotopic cardiac transplantations performed at a single institution, the Texas Heart Institute in Houston, Texas, between 1982 and 2017. Four patients who underwent heterotopic transplantation as an emergency procedure for cardiogenic shock were excluded. Three of the procedures were repeat transplantations in patients who had previously undergone heterotopic transplantation; the 3 repeat transplantations were excluded, but the original procedures were not. Follow-up was 100% complete for mortality and 77% complete (30 of 39 patients) for assessment of preoperative indication for surgery and postoperative cardiac function. RESULTS: For the 39 patients, the 1-year, 5-year, and 10-year survival rates were 69%, 36%, and 21%, respectively. One patient remains alive 25 years after the transplantation procedure. The most frequent indication for heterotopic transplantation was pulmonary vascular resistance greater than 4 Wood units (n = 11), followed by weight greater than 112.5 kg (n = 7). In most patients, native heart left ventricular ejection fraction stabilized over time to between 10% and 30%. Sinus rhythm was preserved in 87% (26 of 30) of native hearts at long-term follow-up. CONCLUSIONS: Heterotopic cardiac transplantation is an acceptable procedure that should be considered for obese patients (especially those heavier than 112.5 kg) and patients with elevated pulmonary vascular resistance (especially those with pulmonary vascular resistance >4.0 Wood units). After heterotopic transplantation, native cardiac function appears to stabilize, and there is potential for native heart recovery.

Investigation of the inherent left-right flow balancing of rotary total artificial hearts by means of a resistance box.

With the incidence of end-stage heart failure steadily increasing, the need for a practical total artificial heart (TAH) has never been greater. Continuous flow TAHs (CFTAH) are being developed using rotary blood pumps (RBPs), leveraging their small size, mechanical simplicity, and excellent durability. To completely replace the heart with currently available RBPs, two are required; one for providing pulmonary flow and one for providing systemic flow. To prevent hazardous states, it is essential to maintain balance between the pulmonary and systemic circulation at a wide variety of physiologic states. In this study, we investigated factors determining a CFTAH's inherent ability to balance systemic and pulmonary flow passively, without active management of pump rotational speed. Four different RBPs (ReliantHeart HA5, Thoratec HMII, HeartWare HVAD, and Ventracor VentrAssist) were used in various combinations to construct CFTAHs. Each CFTAH's ability to autonomously maintain pressures and flows within defined ranges was evaluated in a hybrid mock loop as systemic and pulmonary vascular resistance (PVR) were changed. The resistance box, a method to quantify the range of vascular resistances that can be safely supported by a CFTAH, was used to compare different CFTAH configurations in an efficient and predictive way. To reduce the need for future in vitro tests and to aid in their analysis, a novel analytical evaluation to predict the resistance box of various CFTAH configurations was also performed. None of the investigated CFTAH configurations fully satisfied the predefined benchmarks for inherent flow balancing, with the VentrAssist (left) and HeartAssist 5 (right) offering the best combination. The extent to which each CFTAH was able to autonomously maintain balance was determined by the pressure sensitivity of each RPB: the sensitivity of outflow to changes in the pressure head. The analytical model showed that by matching left and right pressure sensitivity the inherent balancing performance can be improved. These findings may ultimately lead to a reduced need for manual speed changes or active control systems.

Ten-Year Survival With a Continuous-Flow Left Ventricular Assist Device and Aortic Valve Closure.

We report the long-term survival of a 46-year-old man supported with a HeartMate II continuous-flow left ventricular assist device after complex repair of a bicuspid aortic valve, anomalous left main coronary artery, and dilated aorta. He has been maintained on an anticoagulation regimen of warfarin and low-dose aspirin without problems for 10 years, during which he has worked continuously and productively. Device flow has been kept at 10,000 rpm. Possible contributors to this long-term success include proper alignment of the device inflow cannula, pericardial patch closure of the left ventricular outflow tract, and, notably, the remarkable freedom from mechanical failure of the continuous-flow left ventricular assist device. Whether the higher flow rate produced by the pericardial patch closure contributes to pump longevity is unknown and merits further investigation.

Outcomes of Repeat Left Ventricular Assist Device Exchange.

Implantable continuous-flow left ventricular assist devices (CF-LVADs) are used for long-term LV support in bridging patients to heart transplantation or as destination therapy. With prolonged support times, some patients will have repeat complications necessitating multiple device exchanges. To elucidate the safety and efficacy of repeat device exchange, we retrospectively reviewed data from 25 patients who underwent two or more CF-LVAD implantations between July 2005 and August 2017. Indications for exchange were thrombus/hemolysis (n = 8, 32%), electromechanical device malfunction (n = 14, 56%), and infection (n = 3, 12%). The implanted devices were the HeartMate II (n = 13, 52%), the HeartWare HVAD (n = 11, 44%), and the Jarvik 2000 (n = 1, 4%). Average hospital length of stay was 44 days (range 4-221 days), and 17 patients (68%) survived to discharge. Average duration of support after the most recent LVAD implantation was 802 days (range 1-3,229 days). Overall survival was 72% at 1 year and 60% at 2 years. Postoperative complications included respiratory failure in five patients (20%), device infection in five (20%), bleeding requiring reoperation in four (16%), neurologic dysfunction in four (16%), and acute renal failure in two (8%). Overall, our data suggest that repeat LVAD exchange is a feasible option for patients with recurrent device-related complications.

Accuracy of Postoperative Risk Scores for Survival Prediction in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 Continuous-Flow Left Ventricular Assist Device Recipients.

In this study, we sought to determine the accuracy of several critical care risk scores for predicting survival of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile 1 patients after continuous-flow left ventricular assist device (CF-LVAD) placement. We retrospectively analyzed the records of 605 patients who underwent CF-LVAD implantation between 2003 and 2016. We calculated the preoperative HeartMate II Risk Score (HMRS) and preoperative Right Ventricular Failure Risk Score (RVFRS) and the following risk scores for postoperative days 1-5: HMRS, RVFRS, Model for End-stage Liver Disease (MELD), MELD-eXcluding International Normalized Ratio, Post Cardiac Surgery (POCAS) risk score, Sequential Organ Failure Assessment (SOFA) risk score, and Acute Physiology and Chronic Health Evaluation III. The preoperative scores and the postoperative day 1, 5-day mean, and 5-day maximum scores were entered into a receiver operating characteristic curve analysis to examine accuracy for predicting 30-day, 90-day, and 1-year survival. The mean POCAS score was the best predictor of 30-day and 90-day survival (area under the curve [AUC] = 0.869 and 0.816). The postoperative mean RVFRS was the best predictor of 1-year survival (AUC = 0.7908). The postoperative maximum and mean RVFRS and HMRS were more accurate than the preoperative scores. Both of these risk score measurements of acuity in the postoperative intensive care unit setting help predict early mortality after LVAD implantation.