The Future of Durable Mechanical Circulatory Support: Emerging Technological Innovations and Considerations to Enable Evolution of the Field.

The field of durable mechanical circulatory support (MCS) has undergone an incredible evolution over the past few decades, resulting in significant improvements in longevity and quality of life for patients with advanced heart failure. Despite these successes, substantial opportunities for further improvements remain, including in pump design and ancillary technology, perioperative and postoperative management, and the overall patient experience. Ideally, durable MCS devices would be fully implantable, automatically controlled, and minimize the need for anticoagulation. Reliable and long-term total artificial hearts for biventricular support would be available; and surgical, perioperative, and postoperative management would be informed by the individual patient phenotype along with computational simulations. In this review, we summarize emerging technological innovations in these areas, focusing primarily on innovations in late preclinical or early clinical phases of study. We highlight important considerations that the MCS community of clinicians, engineers, industry partners, and venture capital investors should consider to sustain the evolution of the field.

Prehabilitation Using a Cardiac Rehabilitation Program for a Patient With a Total Artificial Heart Prior to Heart Transplantation.

INTRODUCTION: The last few decades have been marked by significant advances in mechanical cardiocirculatory support. A total artificial heart (TAH) became a viable therapeutic option for numerous patients as a bridge to heart transplantation, particularly for those in end-stage heart failure. This technology aims to address the various subsequent shortfalls of organs. This report reviews the impact of a prehabilitation on a patient with an Aeson TAH (Carmat). DISCUSSION: We assessed improvements in functional capacity and quality of life (QoL) in a newly implanted patient following standard cardiac rehabilitation as a prehabilitation program, using 6-min walk test and the Short Form-12 (SF-12) health survey, respectively. Similar functional improvements were observed over a short period of 2 wk compared with a longer protocol for patients with a heart transplant, and superior effects on QoL. The patient was successfully transplanted 5 mo after the TAH implantation. SUMMARY: Prehabilitation of a patient with a TAH increased both their physical capacity and QoL.

Artificial heart valve reinforced with silk woven fabric and poly (ethylene glycol) diacrylate hydrogels composite.

The present study describes the preparation of woven silk fabric (WSF) and poly(ethylene glycol) diacrylate (PEGDA) hydrogel composite reinforced artificial heart valve (SPAHV). Interestingly, the longitudinal and latitudinal elastic modulus of the SPAHV composite can achieve at 54.08 ± 3.29 MPa and 23.96 ± 2.18 MPa, respectively, while its volume/mass swelling ratio and water permeability was 1.9 %/2.8 % and 3 mL/(cm2∙min), respectively, revealing remarkable anisotropic mechanical properties, low water swelling property and water permeability. The in vitro & in vivo biocompatibility and anti-calcification ability of SPAHV were further examined using L929 mouse fibroblasts and Sprague Dawley (SD) male rat model under 8 weeks of subcutaneous implantation. The expression of pro-inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10 was determined by immunohistochemical staining, as well as the H&E staining and alizarin red staining were accessed. The results showed that the composites possess better biocompatibility, resistance to degradation and anti-calcification ability compared to the control group (p < 0.05). Thus, the SPAHV composite with robust mechanical properties and biocompatibility has potential application for artificial heart valves.

End-stage heart failure: The future of heart transplant and artificial heart.

In the last decades, outcomes significantly improved for both heart transplantation and LVAD. Heart transplantation remains the gold standard for the treatment of end stage heart failure and will remain for many years to come. The most relevant limitations are the lack of grafts and the effects of long-term immunosuppressive therapy that involve infectious, cancerous and metabolic complications despite advances in immunosuppression management. Mechanical circulatory support has an irreplaceable role in the treatment of end-staged heart failure, as bridge to transplant or as definitive implantation in non-transplant candidates. Although clinical results do not overcome those of HTx, improvement in the new generation of devices may help to reach the equipoise between the two therapies. This review will go through the evolution, current status and perspectives of both therapeutics.

Hemocompatibility and biophysical interface of left ventricular assist devices and total artificial hearts.

ABSTRACT: Over the past 2 decades, there has been a significant increase in the utilization of long-term mechanical circulatory support (MCS) for the treatment of cardiac failure. Left ventricular assist devices (LVADs) and total artificial hearts (TAHs) have been developed in parallel to serve as bridge-to-transplant and destination therapy solutions. Despite the distinct hemodynamic characteristics introduced by LVADs and TAHs, a comparative evaluation of these devices regarding potential complications in supported patients, has not been undertaken. Such a study could provide valuable insights into the complications associated with these devices. Although MCS has shown substantial clinical benefits, significant complications related to hemocompatibility persist, including thrombosis, recurrent bleeding, and cerebrovascular accidents. This review focuses on the current understanding of hemostasis, specifically thrombotic and bleeding complications, and explores the influence of different shear stress regimens in long-term MCS. Furthermore, the role of endothelial cells in protecting against hemocompatibility-related complications of MCS is discussed. We also compared the diverse mechanisms contributing to the occurrence of hemocompatibility-related complications in currently used LVADs and TAHs. By applying the existing knowledge, we present, for the first time, a comprehensive comparison between long-term MCS options.

Cleveland Clinic Continuous-Flow Total Artificial Heart: Progress Report and Technology Update.

Cleveland Clinic's continuous-flow total artificial heart (CFTAH) is being developed at our institution and has demonstrated system reliability and optimal performance. Based on the results from recent chronic in vivo experiments, CFTAH has been revised, especially to improve biocompatibility. The purpose of this article is to report our progress in developing CFTAH. To improve biocompatibility, the right impeller, the pump housing, and the motor were reviewed for design revision. Updated design features were based on computational fluid dynamics analysis and observations from in vitro and in vivo studies. A new version of CFTAH was created, manufactured, and tested. All hemodynamic and pump-related parameters were observed and found to be within the intended ranges, and the new CFTAH yielded acceptable biocompatibility. Cleveland Clinic's continuous-flow total artificial heart has demonstrated reliable performance, and has shown satisfactory progress in its development.

A Novel Pumping Principle for a Total Artificial Heart.

OBJECTIVE: Total artificial hearts (TAH) serve as a temporary treatment for severe biventricular heart failure. The limited durability and complication rates of current devices hamper long-term cardiac replacement. The aim of this study was to assess the feasibility of a novel valveless pumping principle for a durable pulsatile TAH (ShuttlePump). METHODS: The pump features a rotating and linearly shuttling piston within a cylindrical housing with two in- and outlets. With a single moving piston, the ShuttlePump delivers pulsatile flow to both systemic and pulmonary circulation. The pump and actuation system were designed iteratively based on analytical and in silico methods, utilizing finite element methods (FEM) and computational fluid dynamics (CFD). Pump characteristics were evaluated experimentally in a mock circulation loop mimicking the cardiovascular system, while hemocompatibility-related parameters were calculated numerically. RESULTS: Pump characteristics cover the entire required operating range for a TAH, providing 2.5-9 L/min of flow rate against 50-160 mmHg arterial pressures at stroke frequencies of 1.5-5 Hz while balancing left and right atrial pressures. FEM analysis showed mean overall copper losses of 8.84 W, resulting in a local maximum blood temperature rise of <2 K. The CFD results of the normalized index of hemolysis were 3.57 mg/100 L, and 95% of the pump's blood volume was exchanged after 1.42 s. CONCLUSION AND SIGNIFICANCE: This study indicates the feasibility of a novel pumping system for a TAH with numerical and experimental results substantiating further development of the ShuttlePump.

In Search of the Holy Grail of Artificial Hearts: Are We There Yet?

The total artificial heart (TAH) has a long and rich history, being the product of decades of innovation, hard work, and dedication. This review examines the history of the TAH, a device that has revolutionized the treatment of end-stage biventricular heart failure. It reviews the development of the device from early concepts to the current state-of-the-art device, the SynCardia TAH, which has been implanted in over 2,000 patients worldwide. The article also discusses the challenges and successes experienced by researchers, clinicians, and patients throughout the development of TAH devices. Our focus will also be on discussing the hemostatic alterations in patients implanted with TAH and anticoagulation strategies to decrease associated thromboembolic risks. The article concludes with a look at other novel TAH devices and the future of TAH as an increasingly viable treatment for end-stage heart failure.

Total artificial heart implantation as a bridge to transplantation in the United States.

OBJECTIVES: Although the SynCardia total artificial heart (SynCardia Systems, LLC) was approved for use as a bridge to transplantation in 2004 in the United States, most centers do not adopt the total artificial heart as a standard bridging strategy for patients with biventricular failure. This study was designed to characterize the current use and outcomes of patients placed on total artificial heart support. METHODS: The United Network of Organ Sharing Standard Transplant Research File was queried to identify total artificial heart implantation in the United States between 2005 and 2018. Multivariable Cox regression models were used for risk prediction. RESULTS: A total of 471 patients (mean age, 49 years; standard deviation, 13 years; 88% were male) underwent total artificial heart implantation. Of 161 transplant centers, 11 centers had cumulative volume of 10 or more implants. The 6-month cumulative incidence of mortality on the total artificial heart was 24.6%. The 6-month cumulative incidence of transplant was 49.0%. The 1-year mortality post-transplantation was 20.0%. Cumulative center volume less than 10 implants was predictive of both mortality on the total artificial heart (hazard ratio, 2.2, 95% confidence interval, 1.5-3.1, P < .001) and post-transplant mortality after a total artificial heart bridge (hazard ratio, 1.5, 95% confidence interval, 1.0-2.2, P = .039). CONCLUSIONS: Total artificial heart use is low, but the total artificial heart can be an option for biventricular bridge to transplant with acceptable bridge to transplant and post-transplant survival, especially in higher-volume centers. The observation of inferior outcomes in lower-volume centers raises questions as to whether targeted training, center certifications, and minimum volume requirements could improve outcomes for patients requiring the total artificial heart.

Effects of biventricular shunt on pump characteristics in a maglev total artificial heart.

Severe left ventricular failure can progress to right ventricular failure, necessitating alternatives to heart transplantation, such as total artificial heart (TAH) treatment. Conventional TAHs encounter challenges associated with miniaturization and hemocompatibility owing to their reliance on mechanical valves and bearings. A magnetically levitated TAH (IB-Heart) was developed, utilizing a magnetic bearing. The IB-Heart features a distinctive biventricular shunt channel situated between the flow paths of the left and right centrifugal blood pumps, simplifying and miniaturizing its control system. However, the impact of these shunt channels remains underexplored. This study aimed to investigate the effects of shunt flow on pump characteristics and assess the IB-Heart's potential to regulate flow balance between systemic and pulmonary circulation. At a rotational speed of 2000 rpm and flow rate range of 0-10 L/min, shunt flow exhibited a minor impact, with a 1.4 mmHg (1.3%) effect on pump characteristics. Shunt flow variation of about 0.13 L/min correlated with a 10 mmHg pressure difference between the pumps' afterload and preload conditions. This variance was linked to changes in the inlet flow rates of the left and right pumps, signifying the ventricular shunt structure's capacity to mirror the function of an atrial shunt in alleviating pulmonary congestion. The IB-Heart's ventricular shunt structure enables passive regulation of left-right flow balance. The findings establish a fundamental technical groundwork for the development of IB-Hearts and TAHs with similar shunt structures. The innovative coupling of centrifugal pumps and the resultant effects on flow dynamics contribute to the advancement of TAH technology.

Successful utilization of nirmatrelvir/ritonavir and dexamethasone in a patient with total artificial heart and COVID-19: A case report.

RATIONALE: Management of coronavirus disease 2019 (COVID-19) has been the subject of extensive research and study, leading to the development of strategies and treatments. Nonetheless, there remains a dearth of information concerning patients who require mechanical circulatory system support. This case report presents one of the first documented cases of successful utilization of nirmatrelvir/ritonavir (Paxlovid) and dexamethasone in the treatment of a patient with a total artificial heart. PATIENT CONCERNS: The patient in this case study was a 28-year-old male who had been experiencing severe heart failure. In need of a heart transplant, he underwent a procedure for implantation of a total artificial heart as a bridge to transplantation. DIAGNOSES: Unfortunately, after the surgical intervention, the patient contracted COVID-19, as confirmed by polymerase chain reaction. INTERVENTIONS: The therapeutic approach involved a 5-day regimen of nirmatrelvir/ritonavir at a dosage of 300/100 mg administered twice daily, along with a daily dosage of 6 mg of dexamethasone. OUTCOMES: Remarkably, the patient oxygenation level improved on the second day of therapy. Consequently, he was transferred from the intensive care unit to the general floor. After 71 days with the total artificial heart, the patient successfully underwent heart transplantation. LESSONS: This case report provides a compelling example of the successful application of nirmatrelvir/ritonavir and dexamethasone in the treatment of a COVID-19 patient with a total artificial heart. The positive outcome observed in this case underscores the potential use of these therapeutic agents in this specific patient population. However, it is imperative to conduct further research to corroborate and validate these initial findings. This study lays the foundation for further exploration of the efficacy of these drugs in patients with mechanical circulatory support systems.

Balancing the ventricular outputs of pulsatile total artificial hearts.

BACKGROUND: Maintaining balanced left and right cardiac outputs in a total artificial heart (TAH) is challenging due to the need for continuous adaptation to changing hemodynamic conditions. Proper balance in ventricular outputs of the left and right ventricles requires a preload-sensitive response and mechanisms to address the higher volumetric efficiency of the right ventricle. METHODS: This review provides a comprehensive overview of various methods used to balance left and right ventricular outputs in pulsatile total artificial hearts, categorized based on their actuation mechanism. RESULTS: Reported strategies include incorporating compliant materials and/or air cushions inside the ventricles, employing active control mechanisms to regulate ventricular filling state, and utilizing various shunts (such as hydraulic or intra-atrial shunts). Furthermore, reducing right ventricular stroke volume compared to the left often serves to balance the ventricular outputs. Individually controlled actuation of both ventricles in a pulsatile TAH seems to be the simplest and most effective way to achieve proper preload sensitivity and left-right output balance. Pneumatically actuated TAHs have the advantage to respond passively to preload changes. CONCLUSION: Therefore, a pneumatic TAH that comprises two individually actuated ventricles appears to be a more desirable option-both in terms of simplicity and efficacy-to respond to changing hemodynamic conditions.

Next Generation Development of Hybrid Continuous Flow Pediatric Total Artificial Heart Technology: Design-Build-Test.

To address the unmet clinical need for pediatric circulatory support, we are developing an operationally versatile, hybrid, continuous-flow, total artificial heart ("Dragon Heart"). This device integrates a magnetically levitated axial and centrifugal blood pump. Here, we utilized a validated axial flow pump, and we focused on the development of the centrifugal pump. A motor was integrated to drive the centrifugal pump, achieving 50% size reduction. The motor design was simulated by finite element analysis, and pump design improvement was attained by computational fluid dynamics. A prototype centrifugal pump was constructed from biocompatible 3D printed parts for the housing and machined metal parts for the drive system. Centrifugal prototype testing was conducted using water and then bovine blood. The fully combined device ( i.e. , axial pump nested inside of the centrifugal pump) was tested to ensure proper operation. We demonstrated the hydraulic performance of the two pumps operating in tandem, and we found that the centrifugal blood pump performance was not adversely impacted by the simultaneous operation of the axial blood pump. The current iteration of this design achieved a range of operation overlapping our target range. Future design iterations will further reduce size and incorporate complete and active magnetic levitation.

Patients with Artificial Heart Valves.

BACKGROUND: In Germany, a total of 38 547 heart valve procedures were performed in 2022. With a growing number of patients undergoing the surgical and interventional implantation of heart valves, the incidence of prosthetic endocarditis is also rising. METHODS: We summarize the current state of the prophylaxis, diagnosis, and treatment of prosthetic endocarditis in a selective review of the literature. RESULTS: Prosthetic endocarditis accounts for 10-30% of all cases of endocarditis. As its echocardiographic and microbiologic findings are often less specific than those of native endocarditis, its diagnosis now increasingly relies on alternative imaging modalities such as F-18-FDG PET-CT. Anti-infective and surgical treatment are made more difficult by biofilm formation on the prosthetic valve and the frequent formation of perivalvular abscesses. CONCLUSION: Increased awareness of this clinical entity in the outpatient setting will promote the earlier initiation of appropriate diagnostic studies. Proper diagnostic evaluation is an essential prerequisite for the early detection and timely treatment of prosthetic endocarditis, with the goal of preventing progressive destruction and thus improving the outcome. Preventive and educative measures should be intensified, and certified, multidisciplinary endocarditis teams should be established. Antibiotic prophylaxis is now given much more restrictively than in earlier years; the risk of infection must be weighed against the potential development of both individual and collective resistance to antibiotic drugs.

How do mechanical circulatory support patients die? Autopsy findings for left-ventricular assist device/total artificial heart nonsurvivors.

BACKGROUND: Although life saving for end-stage heart failure patients, permanent mechanical circulatory support (MCS) is often the proximate cause of death in those that do not survive to transplant. Autopsy remains the gold standard for diagnosing causes of death and a vital tool for better understanding underlying pathology of nonsurvivors. The aim of this study was to determine the frequency and outcomes of autopsy investigations and compare these with premortem clinical assessment. METHODS: The autopsy findings and medical records of all patients who underwent left ventricular assist device (LVAD) or total artificial heart (TAH) insertion between June 1994 and April 2022 as a bridge to transplant, but subsequently died pre-heart transplantation were reviewed. RESULTS: A total of 203 patients had a LVAD or TAH implanted during the study period. Seventy-eight patients (M=59, F=19) died prior to transplantation (age 55 [14] years, INTERMACS=2). Autopsies were conducted in 26 of 78 patients (33%). Three were limited studies. The leading contributor to cause of death was respiratory (14/26), either nosocomial infection or associated with multiorgan failure. Intracranial hemorrhage was the second most common cause of death (8/26). There was a major discrepancy rate of 17% and a minor discrepancy rate of 43%. Autopsy study added a total of 14 additional contributors of death beyond clinical assessment alone (Graphical Abstract). CONCLUSIONS: Over an observational period of 26years, the frequency of autopsy was low. To improve LVAD/TAH patient survival to transplant, better understanding as to cause of death is required. Patients with MCS have complex physiology and are at high risk of infection and bleeding complications.

Heart Transplant Outcomes After Total Artificial Heart.

BACKGROUND: We sought to compare heart transplant (HTX) outcomes from patients with a total artificial heart (TAH), biventricular assist device (BiVAD), or left ventricular assist device (LVAD) as a bridge to transplant (BTT). Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)-Scientific Registry of Transplant Recipients (SRTR) created a dataset with TAH or durable mechanical circulatory support (MCS) who reached HTX between 2006 and 2015. METHODS: The retrospective analysis compared TAH outcomes with those with a BiVAD or LVAD before HTX. The primary outcome was posttransplant survival at 1, 36, and 60 months. Secondary outcomes included simultaneous heart-kidney transplants, donor characteristics, and mortality risk factors. INTERMACS-SRTR cohort had, at the time of HTX, 2762 patients with LVAD; 205 BiVAD (139 durable and 66 temporary RVAD); 176 TAH (6 prior HeartMate II). RESULTS: Sixty months after HTX, mortality rates were 16.5% in the total group: LVAD 15.2%, BiVAD 22.4%, and TAH 29%. Survival differed between the LVAD, the TAH, and BiVAD but not between the BiVAD and TAH groups. One-year survival and complication rates were similar across groups-there was no difference in survival by donor age in the overall cohort. There was a difference in TTD based on recipient age in the LVAD group but not in BiVAD or TAH groups. Occurrence of HTX-kidney and post-transplant dialysis were higher in the TAH versus LVAD and BiVAD groups. CONCLUSIONS: The TAH is an efficacious BTT. Refinements in technology and patient selection may improve outcomes.

2001: An artificial heart odyssey.

The quest to replace the natural heart with an artificial one as a permanent system is among the remaining holy grails in medicine and surgery. Beginning in 1969, when the first total artificial heart (TAH) was implanted into a human, to the present, several types have been developed-the AbioCor was among them. On November 5th, 2001, our team at Hahnemann University Hospital in Philadelphia, Pennsylvania placed the world's fifth AbioCor. Excerpts of that moment in time were recorded and serve as a memorial to the past and a testimony to the present and future quest of this elusive holy grail.

Feasibility of Outpatient Hemodialysis for Patients With Total Artificial Heart: A Case Series.

Total artificial hearts (TAH) are used in patients with end-stage heart failure as a bridge-to-transplant. AKI is a common postoperative complication associated with TAH implant. Patients requiring temporary dialysis are denied implantation of TAH due to the inability to provide outpatient (OP) dialysis in the long term. Here we discuss four cases of TAH patients from a single center who were successfully maintained on OP hemodialysis (HD). All four patients were implanted with a 70cc Syncardia TM TAH for NICM. Two patients were implanted as bridge-to-transplant (BTT); one received a heart/kidney transplant and the other received a heart transplant. Two patients were implanted as destination therapy; one was maintained on OP HD until end-of-life, and the other received a heart transplant after becoming transplant eligible. These cases confirm that OP HD is a feasible option for TAH patients with post-implant chronic renal dysfunction provided that the dialysis centers are trained and supported by the implanting program.

Artificial Deep Neural Network for Sensorless Pump Flow and Hemodynamics Estimation During Continuous-Flow Mechanical Circulatory Support.

The objective of this study was to compare the estimates of pump flow and systemic vascular resistance (SVR) derived from a mathematical regression model to those from an artificial deep neural network (ADNN). Hemodynamic and pump-related data were generated using both the Cleveland Clinic continuous-flow total artificial heart (CFTAH) and pediatric CFTAH on a mock circulatory loop. An ADNN was trained with generated data, and a mathematical regression model was also generated using the same data. Finally, the absolute error for the actual measured data and each set of estimated data were compared. A strong correlation was observed between the measured flow and the estimated flow using either method (mathematical, R = 0.97, p < 0.01; ADNN, R = 0.99, p < 0.01). The absolute error was smaller in the ADNN estimation (mathematical, 0.3 L/min; ADNN 0.12 L/min; p < 0.01). Furthermore, strong correlation was observed between measured and estimated SVR (mathematical, R = 0.97, p < 0.01; ADNN, R = 0.99, p < 0.01). The absolute error for ADNN estimation was also smaller than that of the mathematical estimation (mathematical, 463 dynes·sec·cm -5 ; ADNN, 123 dynes·sec·cm -5 , p < 0.01). Therefore, in this study, ADNN estimation was more accurate than mathematical regression estimation. http://links.lww.com/ASAIO/A991.