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.

Extended systemic antibiotic prophylaxis in ventricular assist device recipients, an infectious disease perspective.

OBJECTIVES: To evaluate whether mediastinitis/deep sternal wound infection (Med/DSWI) is more common in ventricular assist device (VAD) with delayed sternal closure (DSC) compared to VAD with primary sternal closure (PSC). METHODS: A literature search was done over the last four decades for studies that addressed this comparison. RESULTS: Two studies met our inclusion criteria, and their results are contradictory. The first study compared 184 VAD recipients with PSC to 180 VAD recipients with DSC. There was no difference in VAD-related infections between DSC and PSC (15% vs. 16%, respectively; odds ratio = 0.965, 95% confidence interval [CI] = 0.525-1.635). The second study compared 464 VAD recipients with PSC to 94 VAD recipients with DSC. The rate of surgical site infection was higher in the DSC patients (12.5% vs. 1.4%, respectively; odds ratio = 10.1; 95% CI = 3.8-27.0). DSC was identified as an independent risk factor for postoperative mortality, but no detailed infection information was given. CONCLUSIONS: There is no clear evidence of the association between DSC, compared to PSC, and Med/DSWI. Therefore, DSC is not an absolute indication for extended systemic antibiotic prophylaxis. The decision to extend the duration of systemic antibiotic prophylaxis should be made on a case-by-case basis, in collaboration with an infectious disease specialist.

Total Artificial Heart Update.

The SynCardia Total Artificial Heart (TAH, SynCardia Systems, Tucson, AZ) is the only biventricular cardiac replacement approved for bridge to transplantation by the U.S. Food and Drug Administration (FDA) and which carries the European Union CE mark. It has been implanted in about 2000 patients. In experienced centers, 60 to 80 % of implanted patients have been transplanted and over 80 % of those transplanted have lived for over 1 year. The SynCardia TAH has supported potential cardiac recipients with irreversible biventricular failure for up to 6 years, providing physiologic pulsatile flows of 6 to 8 L/min at filling pressures of less than 10 mmHg allowing for optimal perfusion and recovery of organs such as the kidneys and liver. It is a tested device that provides a method for recovering potential transplant candidates who rapidly decompensate from biventricular failure or who have chronic cardiac failure from a variety of etiologies. This article covers the history, mechanical function and monitoring, implantation, patient selection and management, and outpatient use. It also reviews outcome data from the original FDA study as well as contemporary data from experienced centers.

Platelet Mapping by Thromboelastography and Whole Blood Aggregometry in Adult Patients Supported by Mechanical Circulatory Support Device on Aspirin Therapy.

Patients on mechanical circulatory support (MCS) devices are placed on aspirin and may require platelet function testing (PFT) to monitor the adequacy of therapy. Routine laboratory PFT is performed using whole blood aggregation (WBA) which typically has a long turnaround time (4-5 hours) and may not be readily available. By contrast, platelet mapping by thromboelastography (TPM) can provide results within 45 minutes. The objective of this study was to compare the results of TPM with WBA. We compared platelet mapping maximal amplitude (MA) by TPM with that of arachidonic acid (AA) to WBA with AA by impedance. We analyzed paired samples where both TPM and WBA were available. Of 45 paired samples, 34 were from 29 MCS patients and 11 were from non-MCS patients. When applying institutional interpretation guidelines with an MAActivator cutoff of ≤40 mm, WBAAA vs TPM MAAA in non-MCS and MCS patients correlated well with an accuracy of 100 and 94.4%, respectively. MAActivator >40 had poor correlation with an accuracy of 37.5%. Irrespective of MAActivator value, TPM AA inhibition expressed in percent of inhibition had poor accuracy. When used with proper guidelines for interpretation, specifically when MAActivator ≤ 40 mm, TPM is a suitable and reliable test to use for MCS patients on aspirin.

Mechanical circulatory support for cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis, typically from abnormal deposition of AL or ATTR amyloid protein, can result in heart failure requiring transplantation (HTx). The role of mechanical circulatory support (MCS) is not well-established. The purpose of this study was to present our experience with MCS in patients with cardiac amyloidosis. METHODS: Consecutive patients with cardiac amyloidosis who received MCS at Cedars-Sinai Medical Center between 2010 and 2018 were reviewed. Clinical characteristics and outcomes were compared to a control group of MCS patients without amyloid matched 2:1 for age and INTERMACS Profile. RESULTS: 11 amyloid patients underwent durable MCS, two with paracorporeal biventricular assist devices and 9 with total artificial hearts. No patients received isolated left ventricular assist device support. By 1 year, 9 (82%) of patients in the MCS-Amyloid group had been transplanted and 2 (18%) had died. In the MCS-No Amyloid group, by 1 year, 8 (36%) of patients had been transplanted, 10 (46%) had died, and 4 (18%) were still living with MCS. CONCLUSIONS: Over a 9-year period, patients with amyloid cardiomyopathy who required MCS at our institution all received durable biventricular MCS. For carefully selected patients, this approach is feasible with acceptable outcomes as bridge to transplantation.

Extracorporeal Membrane Oxygenation Appropriateness: An Interdisciplinary Consensus-Based Approach.

We describe a quality improvement initiative aimed at achieving interdisciplinary consensus about the appropriate delivery of extracorporeal membrane oxygenation (ECMO). Interdisciplinary rounds were implemented for all patients on ECMO and addressed whether care was consistent with a patient's minimally acceptable outcome, maximally acceptable burden, and relative likelihood of achieving either. The rounding process was associated with decreased days on venoarterial ECMO, from a median of 6 days in 2014 (first quartile [Q1]-third quartile [Q3], 3-10) to 5 days in 2015 (Q1-Q3, 2.5-8) and in 2016 (Q1-Q3, 1-8). Our statistical methods do not allow us to conclude that this change was due to our intervention, and it is possible that the observed decreases would have occurred whether or not the rounding process was implemented.

New versatile dual-support pediatric heart pump.

Mechanical circulatory support (MCS) devices for pediatric patients continue to lag in development behind those for adults. There is no heart pump with the design innovation to support dysfunctional states of heart failure and the anatomic heterogeneity of cardiac defects in pediatric patients. To address this unmet need, we are developing a versatile MCS technology with 2 separate blood pumps under 1 housing, whereby a centrifugal pump rotates around an axial pump. In this study, we advanced the design with a new inducer for the axial pump component and flat inlet volute for the centrifugal pump component. We conducted computational modeling of the design iterations, built prototypes, and tested their performance. The axial pump component was able to generate pressure rises of 1-112 mm Hg for 2-5 L/min at 10 000-14 000 RPM, and the centrifugal pump component produced pressure rises of 1-184 mm Hg for 2-5 L/min at 1750-3000 RPM. Shear stresses and blood damage estimations were less than  490 Pa and 0.5%, respectively. Axial and radial forces were also estimated to be less than 5 N for the axially and radially centered impellers. Data sets were repeatable, and data trends followed theoretical expectations. The new designs for the axial and centrifugal pumps enabled us to reduce the height of the pump while maintaining performance expectations. These findings support the continued development of this new medical device for pediatric patients.

Revealing a new mode of sensitization induced by mechanical circulatory support devices: Impact of anti-AT1 R antibodies.

BACKGROUND: Increased levels of angiotensin II type 1 receptor (AT1 R) antibody have been shown to be associated with allograft rejection. This study aims to determine the rate of development of antibody to AT1 R after mechanical circulatory support device (MCS) implantation, and if the development of strong binding AT1 R antibodies is associated with survival. METHODS: Eighty-eight patients who had one MCS implantation were accessed based on serum availability. Mechanical circulatory support devices in this cohort included pneumatic bilateral paracorporeal ventricular assist device, continuous flow left ventricular assist device, and total artificial heart. RESULTS: Of 88 patients, seven patients had AT1 R antibodies ≥40 U/mL preimplantation. For 81 patients who had AT1 R antibodies <40 U/mL, the median value was 8 U/mL. Of these 81 patients, AT1 R antibody levels in 55 (68%) patients reached the saturated concentration (≥40 U/mL) postimplantation (P < .0001), with the highest percentage of patients with the saturated level of AT1 R antibody observed in the pneumatic bilateral paracorporeal ventricular assist device group. Compared to patients without the saturated level of AT1 R antibodies, patients with the saturated AT1 R antibody level had lower 18-month survival (P = .040). CONCLUSION: Mechanical circulatory support devices implantation significantly increases AT1 R antibody levels. The saturated level of AT1 R antibodies is associated with lower patient survival postimplantation.

Hybrid Continuous-Flow Total Artificial Heart.

Clinical studies using total artificial hearts (TAHs) have demonstrated that pediatric and adult patients derive quality-of-life benefits from this form of therapy. Two clinically-approved TAHs and other pumps under development, however, have design challenges and limitations, including thromboembolic events, neurologic impairment, infection risk due to large size and percutaneous drivelines, and lack of ambulation, to name a few. To address these limitations, we are developing a hybrid-design, continuous-flow, implantable or extracorporeal, magnetically-levitated TAH for pediatric and adult patients with heart failure. This TAH has only two moving parts: an axial impeller for the pulmonary circulation and a centrifugal impeller for the systemic circulation. This device will utilize the latest generation of magnetic bearing technology. Initial geometries were established using pump design equations, and computational modeling provided insight into pump performance. The designs were the basis for prototype manufacturing and hydraulic testing. The study results demonstrate that the TAH is capable of delivering target blood flow rates of 1-6.5 L/min with pressure rises of 1-92 mm Hg for the pulmonary circulation and 24-150 mm Hg for the systemic circulation at 1500-10 000 rpm. This initial design of the TAH was successful and serves as the foundation to continue its development as a novel, more compact, nonthrombogenic, and effective therapeutic alternative for infants, children, adolescents, and adults with heart failure.

High Molecular Weight von Willebrand Factor Multimer Loss and Bleeding in Patients with Short-Term Mechanical Circulatory Support Devices: A Case Series.

Acquired von Willebrand syndrome (VWS) due to loss of high-molecular-weight multimers (HMWMs) has been reported with longer term mechanical devices and is associated with mucosal bleeding, a primary hemostasis type of bleeding. However, little is known whether a similar defect occurs in patients with short-term mechanical circulatory support (STMCS) devices. We reviewed von Willebrand factor (VWF) profiles in patients with STMCS devices who underwent VWS workup from December 2015 to March 2017 at an academic quaternary care hospital. There were a total of 18 patients (57.0 ± 12.7 years old; 83.3% male) including nine with mucosal bleeding and nine with decreasing hemoglobin. The STMCS devices included Impella (n = 11), Impella and right ventricular assist device (n = 2), and an extracorporeal membrane oxygenator (n = 5). The mean HMWM by quantitative VWF multimer analysis was 3.6% ± 1.3% (normal cutoff: 18-34%). In all 10 cases in which VWF activity, fibrinogen, factor VIII, or VWF antigen level were obtained, they were either normal or elevated. All cases demonstrated high normal or elevated levels of low molecular weight multimers (LMWMs). These findings are consistent with type 2 VWS (qualitative defect). This is the first study that quantitatively describes STMCS device-associated HMWM loss, which may contribute to mucosal bleeding. This finding may have implications for intraoperative management during implantation of longer term devices or heart transplantation or other surgery while on STMCS.

Role of Methadone in Extracorporeal Membrane Oxygenation: Two Case Reports.

Extracorporeal membrane oxygenation (ECMO) affects pharmacokinetics/dynamics of drugs in unpredictable ways. Anecdotally, ECMO patients require high doses of opioids and sedatives, leading to concerns of tolerance. Methadone is a long-acting synthetic opioid with antagonist properties at the n-methyl-d-aspartate (NMDA) receptor. It has been shown to improve spontaneous breathing trials and weaning from mechanical ventilation; however, there is no literature describing its use in ECMO. We describe two patients from the cardiac surgery intensive care unit at Cedars Sinai (Los Angeles, CA) on ECMO for over 30 days maintained on methadone.

Prevention and Infection Management in Mechanical Circulatory Support Device Recipients.

There are currently no guidelines for the management of infection and its prevention in mechanical circulatory support (MCS) device recipients. The International Society of Heart and Lung Transplantation (ISHLT) has initiated a multidisciplinary collaboration for the creation of a consensus document to guide clinicians in infection prevention and management in MCS patients. Most medical centers use local protocols that are based on expert opinion. MCS recipients are debilitated and have some immunological dysfunction. Over the years there have been technical advancements with smaller devices and drivelines with improved durability. The pulsatile devices have been replaced with newer-generation continuous-flow devices. Patient are living longer with MCSs for bridge to transplant (BTT) and destination therapy (DT). MCS centers have improved patient management by introducing standardized driveline protocols, leading to reduced infection rates among MCS recipients.

Perioperative Care of the Patient With the Total Artificial Heart.

Advanced heart failure continues to be a leading cause of morbidity and mortality despite improvements in pharmacologic therapy. High demand for cardiac transplantation and shortage of donor organs have led to an increase in the utilization of mechanical circulatory support devices. The total artificial heart is an effective biventricular assist device that may be used as a bridge to transplant and that is being studied for destination therapy. This review discusses the history, indications, and perioperative management of the total artificial heart with emphasis on the postoperative concerns.

Device Strategies for Patients in INTERMACS Profiles 1 and 2 Cardiogenic Shock: Double Bridge With Extracorporeal Membrane Oxygenation and Initial Implant of More Durable Devices.

For Interagency Registry for Mechanically Assisted Circulatory Support profiles 1 and 2 cardiogenic shock patients initially placed on extracorporeal membrane oxygenation (ECMO), whether crossover to more durable devices is associated with increased survival, and its optimal timing, are not established. Profiles 1 and 2 patients placed on mechanical support were prospectively registered. Survival and successful hospital discharge were compared between patients placed on ECMO only, ECMO with early crossover, and ECMO with delayed crossover. Survival of patients directly implanted with non-ECMO devices was also reported. One-hundred and sixty-two patients were included. Mean age was 52.2 ± 13.8 years. Seventy-three of 162 (45.1%) were initiated on ECMO. Of these, 43 were supported with ECMO only, 11 were crossed-over early <4 days, and 19 were crossed-over in a delayed fashion. Survival was different across groups (Log-rank P < 0.002). In multivariate analysis, early crossover was associated with decreased mortality as compared with no crossover (hazard ratio [HR] 0.201, 95% confidence interval [95%CI] 0.058-0.697, P = 0.011) or with delayed crossover (HR 0.255, 95%CI 0.073-0.894, P = 0.033). Mortality was not different between delayed crossover and no crossover (P = 0.473). In patients with early crossover there were no deaths at 30 days, and 60-day survival was 90.0 ± 9.5%. Survival to hospital discharge was 72.8%. For patients directly implanted with non-ECMO devices, 30-day and 60-day survival was 90.9 ± 3.1% and 87.3 ± 3.8%, respectively, and survival to hospital discharge was 78.7%. Both initial implant of durable devices and double bridge strategy was associated with improved outcomes. If the double bridge strategy is chosen, early crossover is associated with improved survival and successful hospital discharge.

Safety and Feasibility of Laparoscopic Abdominal Surgery in Patients With Mechanical Circulatory Assist Devices.

Objectives Increasing number of mechanical circulatory assist devices (MCADs) are being placed in heart failure patients. Morbidity from device placement is high and the outcome of patients who require noncardiac surgery after, is unclear. As laparoscopic interventions are associated with decreased morbidity, we examined the impact of such procedures in these patients. Methods A retrospective review was conducted on 302 patients who underwent MCAD placement from 2005 to 2012. All laparoscopic abdominal surgeries were included and impact on postoperative morbidity and mortality studied. Results Ten out of 16 procedures were laparoscopic with 1 conversion to open. Seven patients had a HeartMate II, 2 had Total Artificial Hearts, and 1 had CentriMag. Four patients had devices for ischemic cardiomyopathy and 6 cases were emergent. Surgeries included 6 laparoscopic cholecystectomies, 2 exploratory laparoscopies, 1 laparoscopic colostomy takedown, and 1 laparoscopic ventral hernia repair with mesh. Median age of the patients was 63 years (range, 29-79 years). Median operative time was 123 minutes (range, 30-380 minutes). Five of 10 patients were on preoperative anticoagulation with average intraoperative blood loss of 150 mL (range, 20-700 mL). There were 3 postoperative complications; acute respiratory failure, acute kidney injury and multisystem organ failure resulting in death not related to the surgical procedure. Conclusion The need for noncardiac surgery in post-MCAD patients is increasing due to limited donors and due to more durable and longer support from newer generation assist devices. While surgery should be approached with caution in this high-risk group, laparoscopic surgery appears to be a safe and successful treatment option.

Clinical outcomes in fulminant myocarditis requiring extracorporeal membrane oxygenation: a weighted meta-analysis of 170 patients.

BACKGROUND: Fulminant myocarditis (FM) is often a self-resolving entity if the patient survives the acute illness. Venoarterial extracorporeal membrane oxygenation (ECMO) has been used successfully for treatment of cardiogenic shock or cardiac arrest due to FM. However, clinical outcomes are not well understood, in part because of small study sizes. In the absence of large clinical trials, performance of pooled analysis represents the best method for ascertaining survival rates for ECMO. METHODS: A systematic Medline search was conducted on ECMO for the treatment of FM, updated up to November 2012. Studies with n ≥10 published in the year 2000 or later that reported survival to hospital discharge for FM requiring ECMO were included. Studies that reported only on pediatric patients were excluded. The smaller of studies with overlapping patients were excluded. Cochran Q and I(2) were calculated and reported. RESULTS: Six studies were included in the analysis, encompassing 170 patients. The minimum and maximum reported rates of survival to hospital discharge were 60.0% and 87.5%, respectively. The cumulative rate was 115/170. The calculated Cochran Q value was 3.63, which was not significant for heterogeneity. The I(2) value was 0%. The pooled estimate rate was 66.9% with a 95% confidence interval of 59.4%-73.7%. CONCLUSION: More than two-thirds of patients with FM and either cardiogenic shock and/or cardiac arrest survive to hospital discharge with ECMO. These findings could be used in the risk-benefit analysis when initiation of a cardiopulmonary bypass system is being considered for FM.

Mechanical circulatory support in cardiogenic shock following an acute myocardial infarction: a systematic review.

The significance of the utilization of mechanical circulatory support following a myocardial infarction is not well defined. We present a systematic review of this treatment alternative and suggest guidelines to be considered in the treatment of these patients.

Blood Volume Analysis of Total Artificial Heart Recipients: A Case Series.

Blood volume analysis provides a quantitative volume assessment in patients with equivocal or discordant clinical findings. Reports on its use in mechanical circulatory support are limited and it has never been described in patients with a total artificial heart. Our series demonstrates that patients supported with total artificial heart as a bridge to transplant have significant reductions in red blood cell volume and heterogeneous adaptations in their total blood volume and plasma volume. Pathologic derangements in our patient's total blood volume were targeted to restore euvolemia.

Clinical manifestations and management of left ventricular assist device-associated infections.

BACKGROUND: Infection is a serious complication of left ventricular assist device (LVAD) therapy. Published data regarding LVAD-associated infections (LVADIs) are limited by single-center experiences and use of nonstandardized definitions. METHODS: We retrospectively reviewed 247 patients who underwent continuous-flow LVAD implantation from January 2005 to December 2011 at Mayo Clinic campuses in Minnesota, Arizona, and Florida. LVADIs were defined using the International Society for Heart and Lung Transplantation criteria. RESULTS: We identified 101 episodes of LVADI in 78 patients (32%) from this cohort. Mean age (± standard deviation [SD]) was 57±15 years. The majority (94%) underwent Heartmate II implantation, with 62% LVADs placed as destination therapy. The most common type of LVADIs were driveline infections (47%), followed by bloodstream infections (24% VAD related, and 22% non-VAD related). The most common causative pathogens included gram-positive cocci (45%), predominantly staphylococci, and nosocomial gram-negative bacilli (27%). Almost half (42%) of the patients were managed by chronic suppressive antimicrobial therapy. While 14% of the patients had intraoperative debridement, only 3 underwent complete LVAD removal. The average duration (±SD) of LVAD support was 1.5±1.0 years. At year 2 of follow-up, the cumulative incidence of all-cause mortality was estimated to be 43%. CONCLUSION: Clinical manifestations of LVADI vary on the basis of the type of infection and the causative pathogen. Mortality remained high despite combined medical and surgical intervention and chronic suppressive antimicrobial therapy. Based on clinical experiences, a management algorithm for LVADI is proposed to assist in the decision-making process.