Faculty Bibliography

Proper timing of left ventricular assist device (LVAD) implantation in advanced heart failure patients is not well established and is an area of intense interest. In addition, optimizing LVAD performance after implantation remains difficult and represents a significant clinical need. Implantable hemodynamic monitoring systems may provide physicians with the physiologic information necessary to improve the timing of LVAD implantation as well as LVAD performance when compared with current methods. The CardioMEMS Heart sensor Allows for Monitoirng of Pressures to Improve Outcomes in NYHA Class III heart failure patients (CHAMPION) Trial enrolled 550 previously hospitalized patients with New York Heart Association (NYHA) class III heart failure. All patients were implanted with a pulmonary artery (PA) pressure monitoring system and randomized to a treatment and control groups. In the treatment group, physicians used the hemodynamic information to make heart failure management decisions. This information was not available to physicians for the control group. During an average of 18 month randomized follow-up, 27 patients required LVAD implantation. At the time of PA pressure sensor implantation, patients ultimately requiring advanced therapy had higher PA pressures, lower systemic pressure, and similar cardiac output measurements. Treatment and control patients in the LVAD subgroup had similar clinical profiles at the time of enrollment. There was a trend toward a shorter length of time to LVAD implantation in the treatment group when hemodynamic information was available. After LVAD implantation, most treatment group patients continued to provide physicians with physiologic information from the hemodynamic monitoring system. As expected PA pressures declined significantly post LVAD implant in all patients, but the magnitude of decline was higher in patients with PA pressure monitoring. Implantable hemodynamic monitoring appeared to improve the timing of LVAD implantation as well as optimize LVAD performance when compared with current methods. Further studies are necessary to evaluate these findings in a prospective manner.

The VentriFlo True Pulse Pump (Design Mentor, Inc., Pelham, NH, USA) is the first blood pump designed to mimic human arterial waveforms in a standard oxygenation circuit. Our aim was to demonstrate the feasibility and safety of this pump in preparation for future studies to determine possible clinical advantages. We studied four piglets (41.4-46.2 kg): three with an implanted VentriFlo pulsatile pump and one with the nonpulsatile ROTAFLOW pump (MAQUET Holding B.V. & Co. KG, Rastatt, Germany) as a control. Hemodynamics was monitored during 6-h cardiopulmonary bypass (CPB) support and for 2 h after weaning off CPB. The VentriFlo demonstrated physiologic arterial waveforms with arterial pulse pressure of 24.6 +/- 5.7 mm Hg. Pump flows (2.0 +/- 0.1 L/min in ROTAFLOW; 1.9 +/- 0.1 L/min in VentriFlo) and plasma free hemoglobin levels (27.9 +/- 12.5 mg/dL in ROTAFLOW; 28.5 +/- 14.2 mg/dL in VentriFlo) were also comparable, but systemic O2 extraction (as measured by arterial minus venous O2 saturation) registered slightly higher with the VentriFlo (63.2 +/- 6.9%) than the ROTAFLOW (55.4 +/- 6.5%). Histological findings showed no evidence of ischemic changes or thromboembolism. This pilot study demonstrated that the VentriFlo system generated pulsatile flow and maintained adequate perfusion of all organs during prolonged CPB.

The purpose of this study was to evaluate the effects of sinusoidal pump speed modulation of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) on hemodynamics and pump flow in an awake chronic calf model. The sinusoidal pump speed modulations, performed on the day of elective sacrifice, were set at +/-15 and +/- 25% of mean pump speed at 80 bpm in four awake calves with a CFTAH. The systemic and pulmonary arterial pulse pressures increased to 12.0 and 12.3 mmHg (+/-15% modulation) and to 15.9 and 15.7 mmHg (+/-25% modulation), respectively. The pulsatility index and surplus hemodynamic energy significantly increased, respectively, to 1.05 and 1346 ergs/cm at +/-15% speed modulation and to 1.51 and 3381 ergs/cm at +/-25% speed modulation. This study showed that it is feasible to generate pressure pulsatility with pump speed modulation; the platform is suitable for evaluating the physiologic impact of pulsatility and allows determination of the best speed modulations in terms of magnitude, frequency, and profiles.

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.