Anton Sabashnikov

CentriMag® short-term ventricular assist as a bridge to solution in patients with advanced heart failure: use beyond 30 days

OBJECTIVES Left ventricular assist devices (LVADs) offer very valuable therapeutic options for patients with advanced heart failure. CentriMag (Thoratec, Pleasanton, CA, USA) is an extracorporeal short-term circulatory assist device Conformité Européenne-marked in Europe for use up to 30 days. METHODS Retrospective analysis of 41 patients with advanced heart failure who, from 2003 to 2011, were supported with CentriMag for >30 days as a bridge to recovery, long-term VAD or transplantation. RESULTS Forty-one adult patients were supported with 46 CentriMag devices for a total of 2695 days with a mean support time of 59 (range: 31-167) days. Indications were post-cardiotomy cardiogenic shock (PC = 4), primary graft failure (PGF = 7) and refractory heart failure (RHF = 35). Six devices were used to support the left ventricle, 19 to support the right ventricle and 21 to support both the ventricles (biventricular support considered as single device unit). In the PC cohort, 3 (75%) patients were weaned from support, while 4 (57%) were weaned from support in the PGF cohort. In the RHF cohort, 8 patients were bridged to long-term VAD and 5 were bridged to transplantation; heart function recovered and device explanted in 14, while 8 patients died on support. There were no device failures. Overall, 34 (74%) patients were recovered or bridged, with a 1-year survival of 54%. CONCLUSIONS CentriMag proved to be a versatile, safe and effective short-term circulatory support for patients with advanced heart failure as a bridge to solution. Its use over 30 days is associated with acceptable survival and does not increase device-related complications.

De Novo Aortic Regurgitation After Continuous-Flow Left Ventricular Assist Device Implantation

BACKGROUND Significant aortic regurgitation (AR) after continuous-flow left ventricular assist device (cf-LVAD) placement affects device performance and patient outcomes. This study examined the development of AR and long-term results after implantation of cf-LVADs. METHODS The study included all patients with no or less than mild AR who underwent HeartMate II (58 [62%]; Thoratec Corp, Pleasanton, CA) or HeartWare (35 [38%]; HeartWare International, Framingham, MA) implantation at our institute from July 2006 to July 2012. Serial echocardiograms were obtained preoperatively, at 1, 3 and 6 months postoperatively, and then at a minimum of 4-month intervals in patients with longer-term support. Kaplan-Meier estimates for freedom from moderate or greater AR were generated. Logistic regression analysis was used to define independent predictors of AR after cf-LVAD implantation. RESULTS Median duration of LVAD support was 527 days (25(th), 75(th): 289, 907; range, 60 to 2,433 days). Mild AR developed in 48 patients (51.6%) over a median duration of 126 days, with progression to moderate AR in 13 (14%) over 493 days and to severe AR in 2 (2.1%) over 1,231 days. The incidence of mild or greater AR was 43.1% in HeartMate II vs 65.7% in HeartWare recipients (p = 0.035). Overall freedom from moderate or greater AR was 94.7% ± 2.6% at 1 year, 86.9% ± 4.5% at 2 years, 82.8% ± 5.9% at 3 years, and 31% ± 16.9% at 4 years. Independent predictors of AR were duration of support (odds ratio, 1.002; 95% confidence interval, 1.000 to 1.004; p = 0.017) and a persistently closed aortic valve (odds ratio, 0.193; 95% confidence interval, 0.097 to 0.382; p < 0.001). CONCLUSIONS AR is associated with longer cf-LVAD support duration and persistent aortic valve closure. Incidence of moderate or greater AR after cf-LVAD implantation increases significantly after 3 years. The clinical implications of these data may warrant consideration of prophylactic aortic valve replacement at the time of cf-LVAD implantation, particularly with expected longer duration of support and in patients with preexisting AR that is more than mild.

Bioartificial Heart: A Human-Sized Porcine Model – The Way Ahead

Background A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Native hearts decellularized with preserved architecture and vasculature may provide an acellular tissue platform for organ regeneration. We sought to develop a tissue-engineered whole-heart neoscaffold in human-sized porcine hearts. Methods We decellularized porcine hearts (n = 10) by coronary perfusion with ionic detergents in a modified Langendorff circuit. We confirmed decellularization by histology, transmission electron microscopy and fluorescence microscopy, quantified residual DNA by spectrophotometry, and evaluated biomechanical stability with ex-vivo left-ventricular pressure/volume studies, all compared to controls. We then mounted the decellularized porcine hearts in a bioreactor and reseeded them with murine neonatal cardiac cells and human umbilical cord derived endothelial cells (HUVEC) under simulated physiological conditions. Results Decellularized hearts lacked intracellular components but retained specific collagen fibers, proteoglycan, elastin and mechanical integrity; quantitative DNA analysis demonstrated a significant reduction of DNA compared to controls (82.6±3.2 ng DNA/mg tissue vs. 473.2±13.4 ng DNA/mg tissue, p<0.05). Recellularized porcine whole-heart neoscaffolds demonstrated re-endothelialization of coronary vasculature and measurable intrinsic myocardial electrical activity at 10 days, with perfused organ culture maintained for up to 3 weeks. Conclusions Human-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure.

Distal Limb Perfusion: Achilles' Heel in Peripheral Venoarterial Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is a temporary mechanical circulatory assist method that offers circulatory as well as respiratory support efficiently via peripheral access; however, it is liable to complications. Limb ischemia is one of the notorious complications of ECMO but can be avoided utilizing a proper distal limb perfusion method. A retrospective study of patients undergoing peripheral venoarterial (VA) ECMO for various reasons between June 2010 and December 2012 was performed. All patients were evaluated by our multidisciplinary team for suitability as candidates for ECMO. A peripheral VA-ECMO circuit was implanted via groin: inflow cannula in the femoral vein, an outflow cannula and distal-perfusion cannula, or an introducer sheath in the femoral artery. During the study period, 83 patients underwent various types of ECMO; 45 received peripheral VA-ECMO. Distal limb perfusion was achieved with an introducer sheath (6-8 Fr) in 13 cases and with a distal-perfusion cannula (10-12 Fr) in 32 cases. Nine (20%) patients developed signs of ischemia; five (11.2%) were treated conservatively, while four (8.8%) required surgical intervention. One patient required a below-knee amputation. The incidences of limb ischemia and limb ischemia requiring surgical intervention were significantly higher for the introducer sheath compared with the cannula (30.6 vs. 15.6% and 15.4 vs. 6.25%, respectively). Moreover, the patients supported on ECMO with a distal-perfusion cannula spent a significantly longer time on ECMO compared with the ones in whom an introducer sheath was used (11.9 ± 9.1 vs. 7.7 ± 4.3 days). The mean cannula size was significantly greater than the mean introducer sheath size (11.1 ± 1.3 vs. 7.0 ± 1.1 Fr). Use of a distal-perfusion cannula is a most reliable method of limb perfusion in peripheral VA-ECMO. The cannula can ensure adequate and smooth perfusion of the limb owing to its large caliber, its less turbulent flow, the ability it provides to monitor the flow, and the option to attach a side port.

Long-term results after lung transplantation using organs from circulatory death donors: a propensity score-matched analysis †

OBJECTIVES Due to organ shortage in lung transplantation (LTx), donation after circulatory death (DCD) has been implemented in several countries, contributing to an increasing number of organs transplanted. We sought to assess long-term outcomes after LTx with organs procured following circulatory death in comparison with those obtained from donors after brain death (DBD). METHODS Between January 2007 and November 2013, 302 LTxs were performed in our institution, whereby 60 (19.9%) organs were retrieved from DCD donors. We performed propensity score matching (DCD:DBD = 1:2) based on preoperative donor and recipient factors that were significantly different in univariate analysis. RESULTS After propensity matching, there were no statistically significant differences between the groups in terms of demographics and preoperative donor and recipient characteristics. There were no significant differences regarding intraoperative variables and total ischaemic time. Patients from the DCD group had significantly higher incidence of primary graft dysfunction grade 3 at the end of the procedure (P = 0.014), and significantly lower pO2/FiO2 ratio during the first 24 h after the procedure (P = 0.018). There was a trend towards higher incidence of the need for postoperative extracorporeal life support in the DCD group. Other postoperative characteristics were comparable. While the overall cumulative survival was not significantly different, the DCD group had significantly poorer results in terms of bronchiolitis obliterans syndrome (BOS)-free survival in the long-term follow-up. CONCLUSIONS Long-term results after LTx with organs procured following DCD are in general comparable with those obtained after DBD LTx. However, patients transplanted using organs from DCD donors have a predisposition for development of BOS in the longer follow-up.

Perfusion-Decellularization of Porcine Lung and Trachea for Respiratory Bioengineering

Decellularization of native organs may provide an acellular tissue platform for organ regeneration. However, decellularization involves a trade-off between removal of immunogenic cellular elements and preservation of biomechanical integrity. We sought to develop a bioartificial scaffold for respiratory tissue engineering by decellularization of porcine lungs and trachea while preserving organ architecture and vasculature. Lung-trachea preparations from 25 German Landrace pigs were perfused in a modified Langendorff circuit and decellularized by an SDC (sodium deoxycholate)-based perfusion protocol. Decellularization was evaluated by histology and fluorescence microscopy, and residual DNA quantified spectrophotometrically and compared with controls. Airway compliance was evaluated by endotracheal intubation and mechanical ventilation to simulate physiological breathing-induced stretch. Structural integrity was evaluated by bronchoscopy and biomechanical stress/strain analysis by measuring passive tensile strength, all compared with controls. Decellularized lungs and trachea lacked intracellular components but retained specific collagen fibers and elastin. Quantitative DNA analysis demonstrated a significant reduction of DNA compared with controls (32.8 ± 12.4 μg DNA/mg tissue vs. 179.7 ± 35.8 μg DNA/mg tissue, P < 0.05). Lungs and trachea decellularized by our perfusion protocol demonstrated increased airway compliance but preserved biomechanical integrity as compared with native tissue. Whole porcine lungs-tracheae can be successfully decellularized to create an acellular scaffold that preserves extracellular matrix and retains structral integrity and three-dimensional architecture to provide a bioartifical platform for respiratory tissue engineering.

Ex vivo lung perfusion - state of the art in lung donor pool expansion.

Lung transplantation remains the gold standard for patients with end-stage lung disease. Nevertheless, the number of suitable donor lungs for the increasing number of patients on the waiting list necessitates alternative tools to expand the lung donor pool. Modern preservation and lung assessment techniques could contribute to improved function in previously rejected lungs. Ex vivo lung perfusion (EVLP) already demonstrated its value in identification of transplantable grafts from the higher risk donor pool. Moreover, lungs from EVLP did not show significantly different postoperative results compared to standard criteria lungs. This could be explained by the reduction of the ischemia-reperfusion injury through EVLP application. The aim of this article is to review technical characteristics and the growing clinical EVLP experience with special attention to EVLP application for donation after cardiac death (DCD) lungs.

Risk factors predictive of one-year mortality after lung transplantation

OBJECTIVES Lung transplantation (LTx) is a life-saving therapy for patients with end-stage lung disease. However, there remains a significant postoperative complication rate and mortality in this extreme patient group. The aim of the present study was to identify donor, recipient and perioperative risk factors for one-year mortality after LTx. METHODS A total of 252 LTxs were performed in our institution between 2007 and 2013. Donor and recipient demographics and clinical characteristics of 1-year survivors and non-survivors were collected and compared retrospectively. Multivariate logistic regression analysis was performed on univariate predictors for 1-year mortality with an entry criterion of P < 0.05. RESULTS Multivariate analysis revealed female-to-male transplantation (95% CI: 0.088-0.767; P = 0.015), lower pO2/FiO2-ratio at 72 h postoperatively (95% CI: 0.988-0.999; P = 0.024), need for postoperative extracorporeal membrane oxygenation (ECMO) support (95% CI: 0.035-0.658; P = 0.012) and on-pump technique (95% CI: 0.007-0.944; P = 0.045) as the only independent predictors for 1-year mortality. Mainly unplanned intraoperative conversion to cardiopulmonary bypass contributed to poorer survival in patients who underwent LTx using cardiopulmonary bypass (P < 0.001). CONCLUSIONS Our results show that the unplanned use of CPB (conversion from off- to on-pump) might adversely affect outcome after LTx. Also, the negative impact of female-to-male transplantation should not be underestimated during recipient selection. Furthermore, poor early postoperative oxygenation, particularly with the need for extracorporeal oxygenation, might be a very strong negative prognostic factor after LTx.

Outcomes after implantation of 139 full-support continuous-flow left ventricular assist devices as a bridge to transplantation

OBJECTIVES Left ventricular assist devices (LVADs) are a routine treatment for patients with advanced heart failure as a bridge to transplantation. The aim of this study was to present our institutional experience and mid-term outcomes after implantation of 139 continuous-flow (cf) LVADs as a bridge to transplantation. METHODS One hundred and thirty-nine consecutive LVAD implantations were performed in our institution between July 2007 and August 2013. The mean age of the population was 44.0 ± 13.7 years and 24 (17%) of the patients were female. A substantial number of the patients were on preoperative mechanical support: 35 (25%) with an intra-aortic balloon pump, 9 (6.5%) with an extracorporeal membrane oxygenator and 25 (18%) with previous LVAD, for LVAD exchange. RESULTS The mean support duration was 514 ± 481 days, whereas the longest support duration was 2493 days (>6 years). The overall cumulative survival rate following cfLVAD implantation was 89% at 30 days, 76% at 1 year and 66% at 2 years (Fig. 1). There was a statistically significant difference in survival in favour of first LVAD implantation compared with VAD exchange: 91 vs 80% at 30 days, 79 vs 57% at 1 year and 70 vs 43% at 2 years (log-rank P = 0.010). Postoperatively, patients had a significant improvement in end-organ function 1 month after LVAD implantation. In addition, comparison of two different devices [HeartMate II (HM II) and HeartWare] using propensity score matching showed no significant differences in survival and most postoperative adverse events. However, patients supported with HM II required significantly more units of fresh frozen plasma (P = 0.020) with a trend towards a higher use of red blood cells (P = 0.094), and were also more likely to develop percutaneous site infections (P = 0.022). CONCLUSIONS HM II and HeartWare cfLVADs have excellent early postoperative outcomes and good mid-term survival, despite a considerable number of patients needing VAD exchange.

Influence of Donor Smoking on Midterm Outcomes After Lung Transplantation

BACKGROUND Lung transplantation (LTx) is significantly limited by donor organ shortage. Donor smoking history of more than 20 pack-years is considered an extended donor criterion. In this study, we retrospectively evaluated impact of donor smoking history and extent of smoking on midterm outcome after LTx. METHODS In all, 237 LTx were performed in our institution between 2007 and 2012. Patients were divided into three groups, receiving lungs from 53% nonsmoking donors, 29% smoking donors with fewer than 20 pack-years, and 18% heavy smokers with more than 20 pack-years. RESULTS Preoperative donor and recipient characteristics among the groups were comparable. However, donors from the heavy smokers group were significantly older (p < 0.001). The overall presence of abnormal histology (inflammation or metaplasia) in donor main bronchi samples increased with the extent of smoking but did not reach statistical significance (p = 0.211). Although metaplasia was found in significantly more donors from the heavy smokers group (p = 0.037), this did not translate into inferior outcomes for the recipients. There were no statistically significant differences in PaO2/FiO2 ratio after LTx, duration of mechanical ventilation (p = 0.136), intensive care unit stay (p = 0.133), and total postoperative hospital stay (p = 0.322). One-year and three-year survival were comparable across all three groups (log rank p = 0.151). Prevalence of bronchiolitis obliterans syndrome (p = 0.616), as well as bronchiolitis obliterans syndrome free survival (p = 0.898) after LTx were also comparable. CONCLUSIONS In our experience, history and extent of donor smoking do not significantly affect early and midterm outcomes after LTx. Although this finding does not obviate the need for longer-term observation, donor lungs from even heavy smokers may not per se contraindicate LTx and may provide a valuable avenue for expanding donor organ availability.