Total Artificial Heart Recipients Research Articles

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.

Anticoagulation in syncardia total artificial heart recipients: anti-factor Xa or activated partial thromboplastin time?

Although the activated partial thromboplastin time (aPTT) has historically been the method of choice for anticoagulation monitoring in patients undergoing mechanical circulatory support with intravenous unfractionated heparin, it is being progressively superseded by the anti-factor Xa (anti-Xa) method. A retrospective single-arm, single-centre analysis of 20 patients who underwent total artificial heart implantation entailed simultaneous determinations of aPTT and anti-Xa. Agreement between these parameters was assessed using the Bland–Altman method. Despite a positive correlation between aPTT and anti-Xa, normal target ranges were poorly aligned: from 5th to 30th postoperative day, for anti-Xa values of 0.2 and 0.4 U/ml corresponding aPTT values were 52.1 and 65.2 s, 7.9 and 14.8 lower than predicted values, respectively. This was not associated with thromboembolic sequalae. It was not possible to demonstrate a significant relationship between the predictor variables (postoperative day; white blood cell count; C-reactive protein concentration; alanine transaminase and alkaline phosphatase level; bilirubin; haemoglobin; albumin and total protein concentration) and the agreement between aPTT and anti-Xa levels. In summary, when anti-Xa levels were used to guide anticoagulation therapy, corresponding aPTT levels were low with respect to target range. Methodology applied in this study is generalizable to other forms of mechanical circulatory support.

Agreement between Anti-Factor Xa and Activated Partial Thromboplastin Time Measurements in Syncardia Total Artificial Heart Recipients Receiving Postoperative Anticoagulation with Unfractionated Heparin

<h3>Purpose</h3> The Activated Partial Thromboplastin Time (aPTT) has been the historical method of choice for anticoagulation monitoring in patients undergoing mechanical circulatory support with intravenous unfractionated heparin (IVUFH). However, the assay is susceptible to interference effects and is being progressively superseded by the anti-Factor Xa (anti-Xa) method. The study aim was to investigate the agreement between aPTT and anti-Xa measurements in patients receiving post-operative anticoagulation with IVUFH following Syncardia Inc. Total Artificial Heart (TAH) implantation. <h3>Methods</h3> A retrospective single arm, single centre analysis of 20 patients who underwent TAH implantation from July 2014 to October 2018 entailed simultaneous determinations of aPTT and anti-Xa. Agreement between these parameters was assessed using a novel statistical approach based on the Bland-Altman method. <h3>Results</h3> In spite of a positive correlation between aPPT and anti-Xa measurements, normal target ranges were poorly aligned: from 5^th to 30^th post-operative day, for anti-Xa values of 0.2 and 0.4 U/mL corresponding APTT values were 51.1 and 64.3 seconds, respectively. Moreover, white blood cell count was associated with a trend towards lower aPTT levels with respect to anti-Xa. Conversely, bilirubin level was significantly associated with an increase in aPTT levels with respect to anti-Xa values. <h3>Conclusion</h3> A novel method developed to investigate the agreement between aPTT and anti-Xa in the peri-operative phase of TAH therapy showed comparatively low levels of anticoagulation (with respect to historical target aPTT range) were not associated with thromboembolic sequalae. Methodology developed for this study is generalisable to other forms of mechanical circulatory support.

Peripherally Inserted Central Catheter Placement in a Total Artificial Heart Recipient

Highlights The bedside placement of a peripherally inserted central catheter is contraindicated in patients with a total artificial heart. An emergent situation prohibiting radiographic guidance of central line placement in a patient with a total artificial heart is described. Techniques used to successfully place a peripherally inserted central catheter are noted to help guide clinicians faced with vascular access challenges in a patient with a total artificial heart.

Concordance between Anti-Factor Xa and Activated Partial Thromboplastin Time Measurements in Syncardia Total Artificial Heart Recipients Receiving Postoperative Anticoagulation with Unfractionated Heparin

Activated Partial Thromboplastin Time has been the method of choice for anticoagulation monitoring in patients undergoing mechanical circulatory support with intravenous unfractionated heparin (IVUFH). However, aPTT assay is relatively susceptible to interference effects and is being progressively superseded by the anti-factor Xa (anti-FXa) method. The aim of this study was to identify the determinants of the concordance between aPPT and anti-FXa measurements in Syncardia Total Artificial Heart (TAH) recipients receiving post-operative anticoagulation with IVUH. A retrospective single centre analysis of 20 patients who underwent cardiectomy and TAH implantation from July 2014 to October 2018 entailed the comparison of simultaneous aPTT and anti-FXa measurements. Concordance was assessed analysing paired samples using a novel statistical approach based on the Bland-Altman method. In spite of a positive correlation between aPPT and anti-FXa measurements, normal target ranges were poorly aligned. At anti-Xa values of 0.2 and 0.4 U/mL predicted APTT values were = 51.1 and 64.3 seconds, respectively, slightly lower than expected for in range values of aPTT. APTT was affected by increase in the white cell count showing falsely decreased results when anti-FXa was within range. We describe a novel method to guide the transition from aPTT to anti-FXa for TAH recipients which generalizable to other forms of MCS. We conclude that low levels of anticoagulation were not associated with adverse sequalae because pro-haemorrhagic effects prevail over prothrombotic effects in TAH recipients. The influence of certain markers of infection and hepatic function on concordance provide falsely low aPTT values when anti-FXa is in range.

Successful heart transplantation in patients with total artificial heart infections.

Data are limited on clinical outcomes in patients awaiting heart transplant (HT) with total artificial heart (TAH) infections. We retrospectively reviewed all TAH recipients at our center. TAH infection was classified as definite if a microorganism was isolated in cultures from the exit site or deep tissues around the TAH; as probable in patients without surgical or microbiologic evidence of infection but no other explanation for persistent or recurrent bloodstream infection (BSI); or possible in patients with clinical suspicion and radiographic findings suggestive of TAH infection, but without surgical intervention or microbiologic evidence. From 2012 to 2015, a total of 13 patients received a TAH, with a median age at implantation of 52years (range: 28-60). TAH infection occurred in nine patients (seven definite, one probable, one possible) a median of 41days after implant (range: 17-475). The majority of TAH infections were caused by Staphylococcus species. Seven of nine patients underwent HT (four had pre-HT mediastinal washout, and five had positive HT operative cultures). Three patients had an active BSI caused by the same pathogen causing TAH infection at the time of HT, with one developing a post-HT BSI with the same bacteria. No patient developed post-HT surgical site infection caused by the TAH infection pathogen. No deaths among HT recipients were attributed to infection. TAH infection is frequently associated with BSI and mediastinitis and Staphylococcus was the most common pathogen. A multimodal approach of appropriate pre- and post-HT antimicrobial therapy, surgical drainage, and heart transplantation with radical mediastinal debridement was successful in curing infection.

Appropriate control time constant in relation to characteristics of the baroreflex vascular system in 1/R control of the total artificial heart.

1/R control is a physiological control method of the total artificial heart (TAH) with which long-term survival was obtained with animal experiments. However, 1/R control occasionally diverged in the undulation pump TAH (UPTAH) animal experiment. To improve the control stability of the 1/R control, appropriate control time constant in relation to characteristics of the baroreflex vascular system was investigated with frequency analysis and numerical simulation. In the frequency analysis, data of five goats in which the UPTAH was implanted were analyzed with first Fourier transform technique to examine the vasomotion frequency. The numerical simulation was carried out repeatedly changing baroreflex parameters and control time constant using the elements-expanded Windkessel model. Results of the frequency analysis showed that the 1/R control tended to diverge when very low frequency band that was an indication of the vasomotion frequency was relative high. In numerical simulation, divergence of the 1/R control could be reproduced and the boundary curves between the divergence and convergence of the 1/R control varied depending on the control time constant. These results suggested that the 1/R control tended to be unstable when the TAH recipient had high reflex speed in the baroreflex vascular system. Therefore, the control time constant should be adjusted appropriately with the individual vasomotion frequency.

Ethical Analysis of Withdrawing Total Artificial Heart Support

ObjectivesTo describe the characteristics of patients who undergo withdrawal of total artificial heart support and to explore the ethical aspects of withdrawing this life-sustaining treatment. Patients and MethodsWe retrospectively reviewed the medical records of all adult recipients of a total artificial heart at Mayo Clinic from the program's inception in 2007 through June 30, 2015. Management of other life-sustaining therapies, approach to end-of-life decision making, engagement of ethics and palliative care consultation, and causes of death were analyzed. ResultsOf 47 total artificial heart recipients, 14 patients or their surrogates (30%) requested withdrawal of total artificial heart support. No request was denied by treatment teams. All 14 patients were supported with at least 1 other life-sustaining therapy. Only 1 patient was able to participate in decision making. ConclusionIt is widely held to be ethically permissible to withdraw a life-sustaining treatment when the treatment no longer meets the patient's health care–related goals (ie, the burdens outweigh the benefits). These data suggest that some patients, surrogates, physicians, and other care providers believe that this principle extends to the withdrawal of total artificial heart support.

(683) - Echocardiographic and Hemodynamic Characteristics of Total Artificial Heart Recipients

(683) - Echocardiographic and Hemodynamic Characteristics of Total Artificial Heart Recipients

Total artificial hearts: an overview of post-implantation nursing care for recipients

Heart failure affects more than 750 000 people in the UK ( British Heart Foundation, 2014 ). For many years, heart transplantation has been the definitive end-stage treatment once medical therapy no longer provides adequate symptom management and acceptable quality of life for people experiencing heart failure. The scarcity of donor organs means heart transplantation is not always immediately available so, for those patients with biventricular failure, the options for improving quality and longevity of life are limited. However, an alternative is now available in the form of the total artificial heart (TAH). This article provides an understanding of the history and available models of the TAH, the recipient selection criteria and how TAHs actually function. As the only TAH currently commercially in use in the UK, Australia and the USA, the implantation and nursing care of the SynCardia TAH recipient in both the intensive care unit and ward setting will then be discussed, with consideration given to discharging patients home with a TAH in situ.

Total Artificial Heart Implantation: Clinical Indications, Expected Postoperative Imaging Findings, and Recognition of Complications

The purposes of this article are to review the treatment options for late-stage biventricular heart failure, discuss the clinical indications for total artificial heart (TAH) implantation, illustrate the expected imaging findings after uncomplicated TAH implantation, and highlight the radiologic findings of common and uncommon complications associated with TAH implantation through case examples. TAH implantation is an effective therapeutic option for the treatment of patients with end-stage biventricular heart failure. The duration of implantation varies depending on a particular patient's medical condition and the eventual availability of a human heart for orthotopic transplantation. TAH recipients often undergo imaging with conventional radiography, CT, or both for the assessment of device-related issues, many of which are life-threatening and require emergency management. As the clinical use of the TAH increases and becomes more commonplace, it is imperative that radiologists interpreting imaging studies recognize both the expected and the unexpected imaging findings that affect patient care.

Results with an Anticoagulation Protocol in 99 SynCardia Total Artificial Heart Recipients

For 15 years, we employed a consistent anticoagulation protocol in 99 consecutive SynCardia Systems total artificial heart (TAH) recipients. Thromboelastography and platelet aggregation studies were used for evaluating and modulating therapy with dipyridamole, pentoxiphylline, aspirin, and heparin. Partial thromboplastin times, international normalized ratios, and platelet counts were also followed. After the second post-implant day in patients who were free of endo-device infection (97 patients), the embolic stroke incidence was 0.08 per patient year. This included 23.6 patient years of device support. There were no spontaneous hemorrhagic strokes. Two patients had endo-device infections and both had strokes. Postimplantation bleeding was seen in 20% of patients. All but two of these were within the first postoperative week. In all, 4% of patients had gastrointestinal bleeding. We did not observe heparin-induced thrombocytopenia in any patient. We conclude that stroke rates on TAH support have been low, and recommend this protocol.

The challenge of home discharge with a total artificial heart: the La Pitié Salpêtrière experience

The total artificial heart (TAH) helps to counteract the current decrease in heart donors and is likely to bridge patients to transplant under favourable conditions. Today's mobile consoles facilitate home discharge. The aim of this study was to report on the La Pitie Hospital experience with CardioWest TAH recipients, and more particularly, on generally successful outpatient' management. A retrospective analysis was performed on clinical and biological data from patients implanted with a TAH between December 2006 and July 2010 in a single institution. Morbi-mortality during hospital stay, number and causes of rehospitalizations, quality of life during home discharge, bridge to transplant results and survival have all been analysed. Twenty-seven patients were implanted with the CardioWest. Fifteen patients (55.5%) died during support. Prior to home discharge, the most frequent cause of death was multi-organ failure (46.6%). Twelve patients were discharged home from hospital within a median of 88 days [range 35-152, interquartile range 57] postimplantation. Mean rehospitalization rate was 1.2 by patient, on account of device infection (n = 7), technical problems with the console (n = 3) and other causes (n = 4). Between discharge and transplant, patients spent 87% of their support time out of hospital. All patients who returned home with the TAH were subsequently transplanted, and 1 died in post-transplant. Despite the morbidity and mortality occurring during the postimplantation period, home discharge with a TAH is possible. Portables drivers allow for a safe return home. Aside from some remaining weak points such as infectious complications or noise, CardioWest TAH allows for successful rehabilitation of graft candidates, and assures highly satisfactory transplant results.

Risk factor analysis for survival in CardioWest total artificial heart recipients: A pilot study

Objectives: Little is known about preoperative risk factors for survival after CardioWest total artificial heart (TAH) implantation.

Maintenance of the internal environment in total artificial heart (TAH) recipients during long-term pumping

Sixty-six long-term experiments were performed on animals (65 calves, 1 goat) after implantation with a total artificial heart (TAH). Animal survival ranged from 30 to 314 days using TAH devices ranging from the TNS-BRNO-II to the TNS-BRNO-VIIII. In these experiments some basic problems were studied which need to be overcome to achieve the optimal physiological status of the animal, the optimal maintenance of the internal environment, and the long-term survival of TAH recipients. The problem areas studied were: the vasomotor regulation of the periphery, the prevention of calcification of the driving diaphragms, the optimal regulation of homeostasis, and the pathogenesis and prevention of infection. The basic precondition for the experiments was the problem-free implantation of a TAH and the subsequent optimal method of postoperative care was investigated. By the gradual multifactorial solution of these individual problems, the prolongation of the survival period of experimental animals was achieved. The definite solution and elucidation of some complications during long-term survival is still an open problem because the multifactorial events that influence long-term TAH survival are often very complicated and can sometimes only be solved by overcoming numerous obstacles as a result of the deep functional interrelationships of the disorders present.

Pathogenesis of various forms of infection in artificial hearts

Implanted biomaterials are often inevitably attacked by the bacterial infection. So far this problem has not been sufficiently explained and solved. It represents an ‘evergreen’ in the artificial heart research. Infection of biomaterials is a completely new clinical entity that profoundly differs from the common clinical course of various kinds of infections and their treatment. These infections are persistent; they resist host defense mechanisms and antibiotic therapy because the nature of these microorganisms has changed due to their protection by the biofilm of some bacteria on the surfaces of implanted biomaterials. In our 66 long-term experiments with total artificial heart (TAH) in 25 animals, the infection and sepsis were the main causes of death. The different organs, attacked by the bacterial and septic complications, varied from case to case as the predominant organs, the function of which ceased to be compatible with further survival. The main foci where the infection started were also very variable. The artificial hearts used in these 25 calves were predominantly of TNS-BRNO-VII type (19 animals), TNS-BRNO-II type (4 animals) and of ROSTOCK TAH type (2 animals). The decrease of the immune defense in the TAH recipients of different intensity was evident during the course of infectious process and simultaneously, the virulence and resistance of the microorganisms against antibiotics substantially increased. The activity of the infectious agents was often combined with increased blood coagulation and thrombi formation. In 5 calves hemolytic and hemorrhagic episodes were observed, and in 15 calves without simultaneous anti-calcification treatment, a primary calcification of driving diaphragms was observed. A common dystrophic calcification sometimes complicated septic thrombogenesis. The tactics of the antibiotic therapy differed according to the results of hemocultivation tests and body temperature and was often supported by the stimulation of the immune resistance. In 2 cases we used the coating of blood chamber and driving diaphragm with albumin and hydrophilic polyurethane in order to show whether this changed surface will influence positively or negatively the bacterial seeding on the biomaterial surface. We assume the infections in the TAH recipients to be a multi-factorial process, and therefore the prevention and therapy ought to be also multi-factorial. We tried to respect this approach and we were able to increase the survival from 39 to 293 days.

POSSIBLE MODULATE ANTIDIURETIC HORMONE SECRETION IN RELATION TO CIRCULATING BLOOD VOLUME IN TOTAL ARTIFICIAL HEART IMPLANTED CALVES

Introduction: It has been reported that the circulating blood volume (CBV) increased significantly in total artificial heart (TAH) recipient. Participation of several hormonal factors including antidiuretic hormone (ADH) in this CBV increase has been supposed, yet its detailed mechanism is still unclear. We investigated possible modulation of ADH secretion in TAH recipient in chronic animal experiments. Method: Three calves were implanted with a pneumatic TAH, and the other four calves were implanted only with monitoring lines as controls. After two weeks of postoperative period, two groups were compared in: 1) transition of CBV, plasma ADH level (CADH), and plasma osmolality (Posm), 2) response of CADH to infusion of hyperosmolar saline solution (1M NaCl at 0.1ml/kg/min for 30 min) and to restriction of water intake (2L/day for 3days). Results: The postoperative CBV in a TAH calf significantly increased (130 ± 19 ml/kg), while in the other two TAH calves did not increase (92 ± 13 ml/kg), compared with in control calves (104 ± 19 ml/kg). The postoperative CADH and Posm were within the normal range in all calves (CADH: 1.5 ± 1.0 vs 0.8 ± 0.2 pg/ml, Posm: 273 ± 8 vs 273 ± 7, in TAHs vs controls, respectively). Sensitivity of ADH secretion to Posm elevation in the CBV-increased TAH calf was remarkably suppressed compared with the other, two TAH calves without CBV increase, and the control calves. (0.06 vs 0.55 vs 0.21 pg/ml/mOsm/kg±H2O at hyperosmolar saline infusion, and 0.11 vs. 0.43 vs. 0.55 pg/ml/mOsm/kg±H2O at water intake restriction, respectively). Conclusion: In TAH implanted calves, CBV increases occasionally and the ADH secretion in response to plasma osmolality elevation was modulated concomitantly, these phenomena do not occur consistently.

Etiopathogenesis of hemolytic reactions in total artificial heart recipients.

Hemolysis in total artificial heart (TAH) recipients was analyzed. From a total of 66 long-term experiments lasting from 30-314 days performed in the Brno Research Center, in 53 animals, the total red blood cell (RBC) count, hematocrit, total hemoglobin, and free plasma hemoglobin were investigated. We could essentially divide the whole group of calves in 2 subgroups. The first subgroup was calves with hemolytic reactions, and the second subgroup was calves without any hemolytic reaction at all. In the first subgroup, hemolysis occurred in 47% of the overall number of animals during extracorporeal circulation (ECC), in 15% during ECC and later periodically during the experiment, in 8% during ECC and then continuously during the experiment, and finally in 10% not during ECC but repeatedly during the experiment. In 20% of the animals from the overall number, hemolysis did not occur at all (second subgroup). These results testify to the great individual differences within 1 breed (Bohemian with a substantial component of Holstein). These differences are further modified by exogenous and endogenous factors. First, the inborn resistance of the RBC membrane and also thrombi formation and the mineralization of the driving diaphragm are very important. The extreme situation of decreased RBC membrane resistance was proved using a calf from another breed, the slow growing Scottish Highland breed, which did not survive 22 days of pumping due to intractable lethal hemolysis. These factors are also indicated by the hemolytic action of some drugs (e.g., Dopegyt) used during the experiment for another reason. Also important are the mechanical forces of pumping, surface moieties of the biomaterial, mineralization of the driving diaphragms, thrombi formation, infection, etc. Essentially, the hemolytic reaction in the TAH recipient has a multifactorial character. Hemolysis is undoubtedly an important factor, which can have a profound impact on the length of survival. The experimental and clinical experiences must be continuously integrated, and conclusions valid for human TAH application must be considered as very important for further TAH experimental and clinical research.

Current Functional Status of Symbion Total Artificial Heart Recipients After Transplantation

This multicenter study examines long-term data from the five most experienced North American centers (> 8 total artificial heart [TAH] implants), investigating the functional status of 37 patients who received a Symbion TAH followed by a heart transplant (TX) with post-TX survival > or = 1 year. Primary indications for TAH use included acute cardiogenic shock in 38% (14/37) of patients and deterioration while on the TX waiting list in 35% (13/37). At the time of this study, 86% (32/37) of patients were alive, 94% of whom were functioning at a New York Heart Association (NYHA) classification of I (75% [24/32]) or II (19% [6/32]). NYHA classification before death was I for all five patients who died 40 +/- 17 (r = 14-58) months after transplant. Of the 32 surviving patients, 47% (15) were working, 16% (5) were retired, 12% (4) chose not to work, and 9% (3) were in school. The remaining 16% (5) were unable to work due to surgical limitations. After TX, significant infections occurred in 81% (26/32) of patients and rejection in 72% (23/32). At 1 year after TX, creatinine was within normal limits (< or = 1.4 mg/100 ml or 65-125 mol/L) for 41% (13/32) of patients, 1-2 times normal for 56% (18/32), and > 2 times normal for 3% (1/32). Although TAH is not required for most patients awaiting TX, the device allows excellent long-term functional status in patients otherwise at risk for death. No long-term problems related to the use of temporary mechanical circulatory support were found.

Current Functional Status of Symbion Total Artificial Heart Recipients After Transplantation

Current Functional Status of Symbion Total Artificial Heart Recipients After Transplantation