Faculty Bibliography

Successful implantation of a total artificial heart relies on multiple standardized procedures, primarily the resection of the native heart, and exacting preparation of the atrial and vascular conduits for pump implant and activation. Achieving secure pump connections to inflow/outflow conduits is critical to a successful outcome. During the connection process, however, air may be introduced into the circulation, traveling to the brain and multiple organs. Such air emboli block blood flow to these areas and are detrimental to long-term survival. A correctly managed pump-to-conduit connection prevents air from collecting in the pump and conduits. To further optimize pump-connection techniques, we have developed a novel connecting sleeve that enables airless connection of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) to the conduits. In this brief report, we describe the connecting sleeve design and our initial results from two acute in vivo implantations using a scaled-down version of the CFTAH.

BACKGROUND: Optimal timing of heart transplantation in patients supported with second-generation left ventricular assist devices (LVADs) is unknown. Despite this, patients with LVADs continue to receive priority on the heart transplant waiting list. Our objective was to determine the optimal timing of transplantation for patients bridged with continuous-flow LVADs. METHODS: A total of 301 HeartMate II LVADs (Thoratec Corp, Pleasanton, CA) were implanted in 285 patients from October 2004 to June 2013, and 86 patients underwent transplantation through the end of follow-up. Optimal transplantation timing was the product of surviving on LVAD support and surviving transplant. RESULTS: Three-year survival after both HeartMate II implantation and heart transplantation was unchanged when transplantation occurred within 9 months of implantation. Survival decreased as the duration of support exceeded this. Preoperative risk factors for death on HeartMate II support were prior valve operation, prior coronary artery bypass grafting, low albumin, low glomerular filtration rate, higher mean arterial pressure, hypertension, and earlier date of implant. Survival for patients without these risk factors was lowest when transplant was performed within 3 months but was relatively constant with increased duration of support. Longer duration of support was associated with poorer survival for patients with many of these risk factors. Device reimplantation, intracranial hemorrhage, and postimplant dialysis during HeartMate II support were associated with decreased survival. CONCLUSIONS: Survival of patients supported by the HeartMate II is affected by preoperative comorbidities and postoperative complications. Transplantation before complications is imperative in optimizing survival.

BACKGROUND: Ischemic stroke and intracranial hemorrhage (ICH) following left ventricular assist device (LVAD) placement are major causes of morbidity. The incidence and mortality associated with these events stratified by device type have not been systematically explored. METHODS: A systematic review of PubMed was conducted from January 2007 through June 2016 for all English-language articles involving HeartMate II (HMII) and HeartWare LVAD patients. Ischemic stroke and/or ICH incidence (events per patient-year) and associated mortality rates were abstracted for each device type. RESULTS: Of 735 articles reviewed, 48 (11,310 patients) met inclusion criteria (33 HMII, six HeartWare, eight both devices, and one unspecified). The median duration of device support was 112 days (total 13,723 patient-years). Overall, ischemic stroke or ICH occurred in 9.8% (1110 persons and 0.08 events per patient year [EPPY]). Ischemic stroke occurred in a median of 6.0% or 0.06 EPPY (range 0-16% or 0-0.21 EPPY) of HMII patients versus 7.5% or 0.09 EPPY (range 4-17.1% or 0.01-0.94 EPPY) of HeartWare patients. ICH occurred in a median of 3.0% or 0.04 EPPY (range 0-13.5% or 0-0.13 EPPY) of HMII and 8.0% or 0.08 EPPY (range 3-23% or 0.01-0.56 EPPY) of HeartWare patients. The median mortality rate for LVAD-associated ischemic stroke was 31% (HMII: 33%, [range 2.4-75%] and HeartWare: 11.5% [range 3.9-40%]), and the median mortality rate following ICH was 71% (HMII: 75%, [range 3.9-100%] and HeartWare: 44%, [range 3.1-88%]). CONCLUSIONS: Ischemic stroke and ICH are common after LVAD placement, but heterogeneous event rates are reported in the literature. Given the high associated mortality, further prospective study is warranted.

The unique device architecture of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) requires dedicated and specific air-removal techniques during device implantation in vivo. These procedures comprise special surgical techniques and intraoperative manipulations, as well as engineering design changes and optimizations to the device itself. The current study evaluated the optimal air-removal techniques during the Cleveland Clinic double-ended centrifugal CFTAH in vivo implants (n = 17). Techniques and pump design iterations consisted of developing a priming method for the device and the use of built-in deairing ports in the early cases (n = 5). In the remaining cases (n = 12), deairing ports were not used. Dedicated air-removal ports were not considered an essential design requirement, and such ports may represent an additional risk for pump thrombosis. Careful passive deairing was found to be an effective measure with a centrifugal pump of this design. In this report, the techniques and design changes that were made during this CFTAH development program to enable effective residual air removal and prevention of air embolism during in vivo device implantation are explained.

The benefit of whole-body hypothermia in preventing ischemic injury during cardiac surgical operations is well documented. However, application of hypothermia during in vivo total artificial heart implantation has not become widespread because of limited understanding of the proper techniques and restrictions implied by constitutional and physiological characteristics specific to each animal model. Similarly, the literature on hypothermic set-up in total artificial heart implantation has also been limited. Herein we present our experience using hypothermia in bovine models implanted with the Cleveland Clinic continuous-flow total artificial heart.

BACKGROUND: Stroke is a major cause of mortality after left ventricular assist device (LVAD) placement. METHODS: Prospectively collected data of patients with HeartMate II (n = 332) and HeartWare (n = 70) LVADs from October 21, 2004, to May 19, 2015, were reviewed. Predictors of early (during index hospitalization) and late (post-discharge) ischemic and hemorrhagic stroke and association of stroke subtypes with mortality were assessed. RESULTS: Of 402 patients, 83 strokes occurred in 69 patients (17%; 0.14 events per patient-year [EPPY]): early ischemic stroke in 18/402 (4%; 0.03 EPPY), early hemorrhagic stroke in 11/402 (3%; 0.02 EPPY), late ischemic stroke in 25/402 (6%; 0.04 EPPY) and late hemorrhagic stroke in 29/402 (7%; 0.05 EPPY). Risk of stroke and death among patients with stroke was bimodal with highest risks immediately post-implant and increasing again 9-12 months later. Risk of death declined over time in patients without stroke. Modifiable stroke risk factors varied according to timing and stroke type, including tobacco use, bacteremia, pump thrombosis, pump infection, and hypertension (all p < 0.05). In multivariable analysis, early hemorrhagic stroke (adjusted odds ratio [aOR] 4.3, 95% confidence interval [CI] 1.0-17.8, p = 0.04), late ischemic stroke (aOR 3.2, 95% CI 1.1-9.0, p = 0.03), and late hemorrhagic stroke (aOR 3.7, 95% CI 1.5-9.2, p = 0.005) predicted death, whereas early ischemic stroke did not. CONCLUSIONS: Stroke is a leading cause and predictor of death in patients with LVADs. Risk of stroke and death among patients with stroke is bimodal, with highest risk at time of implant and increasing risk again after 9-12 months. Management of modifiable risk factors may reduce stroke and mortality rates.

INTRODUCTION: Heart failure (HF) remains a major global burden in terms of morbidity and mortality. Despite advances in pharmacological and resynchronization device therapy, many patients worsen to end-stage HF. Although the gold-standard treatment for such patients is heart transplantation, there will always be a shortage of donor hearts. Areas covered: A left ventricular assist device (LVAD) is a valuable option for these patients as a bridge measure (to recovery, to candidacy for transplant, or to transplant itself) or as destination therapy. This review describes the current indications for and complications of the most commonly implanted LVADs. In addition, we review the potential and promising new LVADs, including the HeartMate 3, MVAD, and other LVADs. Studies investigating each were identified through a combination of online database and direct extraction of studies cited in previously identified articles. Expert commentary: The goal of LVADs has been to fill the gap between patients with end-stage HF who would likely not benefit from heart transplantation and those who could benefit from a donor heart. As of now, the use of LVADs has been limited to patients with end-stage HF, but next-generation LVAD therapy may improve both survival and quality of life in less sick patients.

INTRODUCTION: A modern ventricular assist device (VAD) system comprises an implantable rotary blood pump and external components located outside the patient's body: a wearable controller connected to the pump via a percutaneous cable, wearable rechargeable batteries, battery charger, alternating- and direct-current power supplies, and a hospital device to control and monitor the system. If the blood pump is the 'heart' of a VAD system, the controller is its 'brain.' The controller drives the pump's electrical motor; varies the pump speed or flow based on user commands or feedback signals; collects, processes, and stores data; performs self-diagnostics; transmits to and receives data from other system components, i.e., hospital monitor and batteries; and provides various types of user interface - audible, visual, and tactile. Areas covered: Here we describe the essential functions and basic design of the VAD external controller and give our views on the future of this technology. Expert commentary: Controllers for VAD systems are crucial to their successful operation. The current clinically available system comprises an external power supply and patient-friendly controller unit. Future controller solutions may enable remote hospital monitoring, more intuitive system interface, and the potential to use a single controller to automatically control a biventricular assist device configuration.

Cleveland Clinic's continuous-flow total artificial heart (CFTAH) provides systemic and pulmonary circulations using one assembly (one motor, two impellers). The right pump hydraulic output to the pulmonary circulation is self-regulated by the rotating assembly's passive axial movement in response to atrial differential pressure to balance itself to the left pump output. This combination of features integrates a biocompatible, pressure-balancing regulator with a double-ended pump. The CFTAH requires no flow or pressure sensors. The only control parameter is pump speed, modulated at programmable rates (60-120 beats/min) and amplitudes (0 to +/-25%) to provide flow pulses. In bench studies, passive self-regulation (range: -5 mm Hg