Technology and technique for left ventricular assist device optimization: A Bi-Tech solution.

BACKGROUND: We investigated the synergistic effect of the new cone-bearing design of Jarvik 2000 (Jarvik Heart Inc., NY) together with a minimally-invasive approach to outcomes of LVAD patients. METHODS: We retrospectively reviewed all patients from 5 institutions involved in the Jarvik 2000 Italian Registry, from October 2008 to October 2016. Patients were divided into three groups according to pump design and implantation technique: pin-bearing design and conventional approach (Group 1); cone-bearing and conventional approach (Group 2); cone-bearing and minimally-invasive implantation (Group 3). RESULTS: A total of 150 adult patients with end-stage heart failure were enrolled: 26 subjects in Group 1, 74 in Group 2, and 50 in Group 3. Nineteen patients (73%) in Group 1, 51 (69%) in Group 2, and 36 (72%) in Group 3 were discharged. During follow-up, 22 patients underwent transplantation, while in 3 patients the LVAD was explanted. The overall 1-year survival was 58 ± 10%, 64 ± 6%, and 74% ± 7% in Groups 1, 2, and 3, respectively (p = 0.034). The competing-risks-adjusted cumulative incidence rate for adverse events was 42.1 [27-62.7] per 100 patient-years in Group 1, 35.4 [25.3-48.2] in Group 2, and 22.1 [12.4-36.4] in Group 3 (p = 0.046 for Group 1 vs. 3). CONCLUSIONS: The association of the modern cone-bearing configuration of Jarvik 2000 and minimally invasive surgery improved survival and minimized the risk for cardiovascular events, as a result of combining technology and technique.

From bench to bedside: Impact of left ventricular assist device outflow conduit anastomosis position on outcome.

Continuous flow left ventricular assist devices (LVADs) have become a valuable therapy for end-stage heart failure. In vitro research highlighted a role of outflow cannula position on the pattern of blood flow in the aorta. However, the clinical effects of the alterations of flow remain unclear. We investigate short- and long-term outcomes of patients implanted with Jarvik 2000 LVAD, according to the ascending (Group 1) versus descending (Group 2) outflow graft connection to the aorta in a multicenter study. From May 2008 to October 2014, 140 consecutive end-stage heart failure patients underwent Jarvik 2000 LVAD implantation in 17 Italian centers. According with a preliminary multivariate analysis, we selected the 90 patients implanted in the four high-volume centers to avoid bias (Group 1 n = 39, Group 2 n = 51). Among the groups, no differences were recorded in the hospital mortality and the main complications occurring after LVAD implantation were similar. In multivariable analysis, the ascending aorta outflow cannula position and higher creatinine at discharge were significant predictors for long-term survival. Postimplant hemolysis was more pronounced in descending aorta outflow graft anastomosis. Outflow graft anastomosis to the ascending aorta is associated with better long-term survival, independent of age and perfusion techniques, reflecting the previous in vitro results.

The Biocompatibility Challenges in the Total Artificial Heart Evolution.

There are limited therapeutic options for final treatment of end-stage heart failure. Among them, implantation of a total artificial heart (TAH) is an acceptable strategy when suitable donors are not available. TAH development began in the 1930s, followed by a dramatic evolution of the actuation mechanisms operating the mechanical pumps. Nevertheless, the performance of TAHs has not yet been optimized, mainly because of the low biocompatibility of the blood-contacting surfaces. Low hemocompatibility, calcification, and sensitivity to infections seriously affect the success of TAHs. These unsolved issues have led to the withdrawal of many prototypes during preclinical phases of testing. This review offers a comprehensive analysis of the pathophysiological events that may occur in the materials that compose TAHs developed to date. In addition, this review illustrates bioengineering strategies to prevent these events and describes the most significant steps toward the achievement of a fully biocompatible TAH.

Lvad pump speed increase is associated with increased peak exercise cardiac output and vo2, postponed anaerobic threshold and improved ventilatory efficiency.

BACKGROUNDS: Peak exercise cardiac output (CO) increase is associated with an increase of peak oxygen uptake (VO2), provided that arteriovenous O2 difference [Δ(Ca-Cv)O2] does not decrease. At anaerobic threshold, VO2, is related to CO. We tested the hypothesis that, in heart failure (HF) patients with left ventricular assistance device (LVAD), an acute increase of CO obtained through changes in LVAD pump speed is associated with peak exercise and anaerobic threshold VO2 increase. METHODS: Fifteen of 20 patients bearing LVAD (Jarvik 2000) enrolled in the study successfully performed peak exercise evaluation. All patients had severe HF as shown by clinical evaluation, laboratory tests, echocardiography, spirometry with alveolar-capillary diffusion, and maximal cardiopulmonary exercise testing (CPET). CPETs with non-invasive CO measurements at rest and peak exercise were done on 2days at LVAD pump speed set randomly at 2 and 4. RESULTS: Increasing LVAD pump speed from 2 to 4 increased CO from 3.4±0.9 to 3.8±1.0L/min (ΔCO 0.4±0.6L/min, p=0.04) and from 5.3±1.3 to 5.9±1.4L/min (ΔCO 0.6±0.7L/min, p<0.01) at rest and peak exercise, respectively. Similarly, VO2 increased from 788±169 to 841±152mL/min (ΔVO2 52±76mL/min, p=0.01) and from 568±116 to 619±124mL/min (ΔVO2 69±96mL/min, p=0.02) at peak exercise and at anaerobic threshold, respectively. Δ(Ca-Cv)O2 did not change significantly, while ventilatory efficiency improved (VE/VCO2 slope from 39.9±5.4 to 34.9±8.3, ΔVE/VCO2 -5.0±6.4, p<0.01). CONCLUSIONS: In HF, an increase in CO with a higher LVAD pump speed is associated with increased peak VO2, postponed anaerobic threshold, and improved ventilatory efficiency.

In vitro performance investigation of SynCardia™ Freedom® driver via patient simulator mock loop.

PURPOSE: The gold standard therapy for patients with advanced heart failure is heart transplant. The gap between donors and patients in waiting lists promoted the development of circulatory support devices, such as the total artificial heart (TAH). Focusing on in vitro tests performed with CardioWest™ TAH (CW) driven by the SynCardia Freedom® portable driver (FD) the present study goals are: i) prove the reliability of a hydraulic circuit used as patient simulator to replicate a quasi-physiological scenario for various hydrodynamic conditions, ii) investigate the hydrodynamic performance of the CW FD, iii) help clinicians in possible interpretation of clinical cases outcomes. METHODS: In vitro tests were performed using a mechanic-hydraulic patient simulator. Cardiac output (CO), CW ventricles filling, atrial, ventricles, aortic and pulmonary artery pressures were measured for different values of vascular resistance in both systemic (SVR) and pulmonary (PVR) physiological range. RESULTS: After increasing the PVR, the left atrial pressure decreased according to the expected physiological trend, while aortic pressure remained almost stable, proving the ability of the simulator to mimic a physiological scenario. Unexpectedly, the mean pulmonary artery pressure (PPA) was found to increase above 30 mmHg in the range of physiological PVR (2.6 WU) and for constant CO. CONCLUSIONS: The increase in PPA is probably associated with the pre-set driving setup of the FD. The finding suggests a possible explanation of the clinical course of a patient who experienced complications soon after being supported by the FD, with the occurrence of dyspnea and pulmonary edema despite a high cardiac index.

From bench to bedside: Can the improvements in left ventricular assist device design mitigate adverse events and increase survival?

OBJECTIVE: In vitro tests demonstrated that the new cone-bearing configuration of the Jarvik 2000 (Jarvik Heart Inc, New York, NY) left ventricular assist device exhibits better hydraulic efficiency than the previous pin-bearing design. We investigated the long-term outcomes of patients who received the Jarvik 2000 left ventricular assist device, depending on bearing design. METHODS: A retrospective review of prospectively collected data from 18 centers included in the Italian Registry was performed. From May 2008 to September 2013, 99 patients with end-stage heart failure were enrolled. Patients were divided into 2 groups according to their Jarvik 2000 suspending mechanism: Group pin included patients with pin bearings (May 2008 to June 2010), and group cone included patients with newer cone bearings (July 2010 to September 2013). The 2 groups did not differ significantly in terms of baseline characteristics. RESULTS: A total of 30 of 39 patients (group pin) and 46 of 60 patients (group cone) were discharged. During follow-up, 6 patients underwent transplantation, and in 1 patient the left ventricular assist device was explanted. The cumulative incidence competing risk of the entire cohort for noncardiovascular-related death was 28% (20%-40%); the cumulative incidence competing risk for cardiovascular-related death was 56% (42%-73%): 71% in group pin versus 26% in group cone (P = .034). The multivariate analyses confirmed that the pin-bearing design was a risk factor for cardiovascular death, along with Interagency Registry for Mechanically Assisted Circulatory Support class. Right ventricular failures and ischemic and hemorrhagic strokes were significantly higher in group pin. CONCLUSIONS: Patients with the new pump configuration showed a better freedom from cardiovascular death and lower incidence of fatal stroke and right ventricular failure. Further studies are needed to prove the favorable impact of pump-enhanced fluid dynamics on long-term results.

Present and future perspectives on total artificial hearts.

Due to shortages in donor organ availability, advanced heart-failure patients are at high risk of further decompensation and often death while awaiting transplantation. This shortage has led to the development of effective mechanical circulatory support (MCS). Currently, various implantable ventricular-assist devices (VADs) are able to provide temporary or long-term circulatory support for many end-stage heart-failure patients. Implantation of a total artificial heart (TAH) currently represents the surgical treatment option for patients requiring biventricular MCS as a bridge to transplant (BTT) or destination therapy (DT). However, the clinical applicability of available versions of positive displacement pumps is limited by their size and associated complications. Application of advanced technology is aimed at solving some of these issues, attempting to develop a new generation of smaller and more effective TAHs to suit a wider patient population. Particular targets for improvement include modifications to the biocompatibility of device designs and materials in order to decrease hemorrhagic and thromboembolic complications. Meanwhile, new systems to power implanted driving units which are fully operational without interruption of skin barriers represent a potential means of decreasing the risk of infections. In this review, we will discuss the history of the TAH, its development and clinical application, the implications of the existing technological solutions, published outcomes and the future outlook for TAHs.

Initial results of clinical trial with a new left ventricular assist device (LVAD) providing synchronous pulsatile flow.

OBJECTIVES: A multicentric European Clinical Study is ongoing to evaluate safety and efficacy of a new pulsatile implantable LVAD (BestBeat), smaller and lighter than similar devices, capable of providing synchronous and counterpulsating flow with respect to the LV of end-stage heart failure patients. Preliminary clinical results are reported. METHODS: The new BestBeat LVAD was used, consisting of an implantable pulsatile blood pump, electromechanically driven by a ball screw mechanism, and a wearable electronic controller and power sources. The clinical trial was conducted at 5 european centers. Adult patients affected by CHF in NYHA Class IV despite optimized medical treatment were enrolled. The primary study endpoint was survival at 90 days. Further study endpoints were maintenance of adequate LVAD pump flow and a minimum rate of adverse events during support. RESULTS: As of June 2008, 6 patients received the implant. Cumulative support time was 3.7 years, median support time 176 days. All patients who completed the study survived except for one, who died after 48 days, due to combined infection and cerebrovascular accident. Another two patients died: one from intracranial bleeding 113 days after implant, and one from septic shock after 123 days. Hemodynamic improvement with CI>2.0 l/min/m2 and recovery of end-organ function expressed by consistent improvement of BUN, creatinine and bilirubin were reached in all patients. No device failure was observed. There was no bleeding requiring re-exploration, no hemolysis and only two device-related infections (both in one patient). Neurologic events were reported, the most serious ones occurring in patients with pre-implant respiratory and kidney failure. Three patients were discharged home. Two patients were successfully transplanted, one after 6 months and one after 13 months on device. CONCLUSIONS: Good performance and efficacy of the device were observed; the endpoints of the study were achieved, and its safety was consistent with expectations. The ongoing study will allow further conclusions to be drawn.