Ex vivo lung perfusion made easy.

Ex vivo lung perfusion is an indispensable tool in the armamentarium of any lung transplant center. It helps to increase an already shrinking donor pool by offering a chance to assess suboptimal donor lungs in a systematic manner and improve them by treating them with low-molecular-weight perfusate. We offer a stepwise guide to carry out ex vivo lung perfusion on the donor lungs and criteria to accept them for transplants.

Use of oxygenator with short-term ventricular assist devices.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) serves as a conventional short-term mechanical circulatory assist to support heart and lung functions. The short-term ventricular assist devices (ST-VAD) can, on the contrary, offer only circulatory support. A combination of VAD and oxygenator (Oxy-VAD) could help overcome this potential disadvantage. This is a retrospective case note study of patients supported on ST-VAD which required adding an oxygenator for extra respiratory support. The oxygenator was introduced in the ST-VAD circuit, either on the left or the right side. Twenty-two patients with the etiology of refractory cardiogenic shock in decompensation were supported on Oxy-VAD between years 2009 and 2019 at tertiary care . All patients were classified into class-I INTERMACS with a mean SOFA Score of 14 ± 2.58. 86.4% of patients were already on mechanical support pre-ST-VAD implant, 80% on VA-ECMO. The BiVAD implant accounted for 63.6%, followed by LVAD and RVAD with 27.3% and 9.1%. Mean duration of the ST-VAD was 8.5 days. The oxygenator was introduced in 14 RVAD and 8 LVAD circuits. The oxygenator was successfully weaned in 54.5% while ST-VAD was explanted in 31.8%. Discharge to home survival was 22.7%. Oxy-VAD proves a viable, and probably, a better option to VA-ECMO in acute cardiorespiratory decompensation. It offers organ-specific tailor-made support to the right and/or left heart and/or lungs. While on Oxy-VAD support, each organ performance can be assessed independently, and the assistance of the specifically improved organ can be weaned off without discontinuing the support for the rest.

The role of extracorporeal life support in the management with severe idiopathic pulmonary artery hypertension undergoing lung transplantation: are those patients referred too late?

BACKGROUND: Idiopathic pulmonary artery hypertension (iPAH) is a relatively minor indication for lung transplantation (LTx) with comparatively poorer outcomes. Extracorporeal life support (ECLS) in various forms is increasingly being used in the management of this entity. However, the data and experience with this therapy remains limited. We evaluated the role of ECLS in the management of severe iPAH patients as a bridge to LTx as well as post LTx support. METHODS: A retrospective analysis of iPAH patients that received LTx between January 2007 and May 2014 was performed. Early- and mid-term outcomes were analyzed for this patient cohort. Also, early and mid-term outcomes after LTx were compared to the control group of patients with other diagnoses using unadjusted analysis and 1:3 propensity score matching. RESULTS: Of 321 LTx performed during the study period in our centre 15 patients had iPAH as a cause of end-stage lung disease. Four iPAH (27%) patients were bridged to LTx utilizing ECLS in the form of veno-arterial ECMO and extra-corporeal CO2 removal device, whereas 9 patients (60%) required ECLS support for primary graft dysfunction (PGD) after surgery. Patients with iPAH required more frequently on-pump LTx, both pre and post LTx ECLS, and had significantly lower pO2/FiO2 ratio at 24, 48 and 72 hours after LTx. Also iPAH patients had significantly longer ICU and hospital stay. Whereas the incidence of postoperative bronchiolitis obliterans syndrome (BOS) and rejection was comparable to the control group, overall cumulative survival with up to 6 years follow-up was significantly poorer in the iPAH group. After propensity score matching, the results in terms of postoperative outcomes remained as in the unadjusted analysis. CONCLUSIONS: ECLS is an essential tool in the armamentarium of any lung transplant program treating iPAH with a potential of bridge patients to transplantation and to overcome graft dysfunction after LTx. Despite utilization of ECLS in the management of iPAH, the outcomes in terms of primary graft failure and survival remain poor compared to patients with other diagnoses.

Minimally Invasive Left Ventricular Assist Device Implantation: A Comparative Study.

Left ventricular assist device (LVAD) is now a routine therapy for advanced heart failure. Minimally invasive approach via thoracotomy for LVAD implantation is getting popular due to its potential advantage over the conventional sternotomy approach in terms of reduced risk at re-operation due to sternal sparing. We compared the approaches (thoracotomy and sternotomy) to determine the superiority. Minimally invasive approach involved fitting of the LVAD inflow cannula into left ventricle apex via left anterior thoracotomy and anastomosis of outflow graft to ascending aorta via right anterior thoracotomy. In the sternotomy approach, both the procedures were performed via sternotomy. Outcomes in patients after LVAD implantation were compared depending on these approaches for the surgery. Two hundred and five continuous flow LVAD implantations performed between July 2006 and June 2015 at a single center were divided based on surgical approach, that is, sternotomy (n = 180) and thoracotomy (n = 25) groups. There was no significant difference between the groups in relation to patient demographics, preoperative hemodynamic parameters, laboratory markers, or risk factors. There was no significant difference between the groups in terms of postoperative hemodynamic parameters, laboratory markers, bleeding and requirement of blood products, intensive care unit, and hospital stay or complications of LVAD surgery. There were no significant differences in terms of long-term survival (Log-Rank P = 0.953), however, thoracotomy, compared to sternotomy approach, incurred significantly less requirement of temporary right ventricular assist (4 vs. 19.4%, P = 0.041). Minimally invasive bilateral thoracotomy approach for LVAD implantation in addition to benefits of sternal sparing avoids dilatation of right ventricle and reduces chances of right ventricular failure requiring temporary right ventricular assist.

Comparison of temporary ventricular assist devices and extracorporeal life support in post-cardiotomy cardiogenic shock.

OBJECTIVES: Post-cardiotomy cardiogenic shock (PCCS) results in substantial morbidity and mortality, whereas refractory cases require mechanical circulatory support (MCS). The aim of the study was to compare extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VADs) utilized in the management of PCCS. METHODS: In total, 56 consecutive patients who developed PCCS from 2005 to 2014 required MCS as a bridge to decision-24 were supported with a VAD and 32 with an ECMO. Groups were compared with respect to pre- and intraoperative characteristics and early and long-term outcomes to evaluate the impact of the type of MCS on complications and survival. Data are mean ± standard deviation and median with quartiles. RESULTS: EuroSCORE II was significantly higher in the VAD group than in the ECMO group (28 ± 20 vs 13 ± 16, P = 0.020) corresponding to significantly higher New York Heart Association (P = 0.031) class and Canadian Cardiovascular Society class (P = 0.040) in the cohort. The median duration of support was 10 (4-23) and 7 (4-10) days in the VAD and ECMO groups, respectively. There were no significant differences in ITU (P = 0.262), hospital stay (P = 0.193) and incidences of most postoperative complications. A significantly higher proportion of patients was successfully weaned/upgraded in the VAD group [13 (54%) vs 4 (13%), P = 0.048] with a trend towards higher discharge rate [9 (38%) vs 5 (16%), P = 0.061]. Overall cumulative survival in early follow-up [Breslow (Generalized Wilcoxon) P = 0.017] and long-term follow-up [Log-rank (Mantel-Cox) p = 0.015] was significantly better in the VAD group. CONCLUSIONS: VAD and ECMO represent essential tools to support patients with PCCS. Our preliminary results might indicate some benefits of using VAD in this group of patients; however, this evidence should be further assessed in larger multicentre trials.

Suicidal hanging donors for lung transplantation: Is this chapter still closed? Midterm experience from a single center in United Kingdom.

In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group.Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed.No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P < .001, P = .022 and P = .0042, respectively). Recipient preoperative and perioperative characteristics were comparable. Postoperatively in group 1 there was a higher incidence of extracorporeal life support (27.3 vs 9.1%, P = .019). There were no significant differences in chronic lung allograft dysfunction-free survival between group 1 and 2: 92.3 vs 94% at 1 year and 65.9 vs 75.5% at 3 years (P = .99). The estimated cumulative survival rate was also similar between groups: 68.2 vs 83.2% at 1 year and 68.2% versus 72% at 3 years (P = .3758).Hanging as a donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation.

Influence of history of cannabis smoking in selected donors on the outcomes of lung transplantation.

OBJECTIVES: Cannabis is the most commonly abused illicit drug and the smokers are at the risk of lung infections, bullous emphysema and lung cancer. However, no evidence about the outcomes of lung transplantation (LTx) utilizing the lungs from such donors is available in the literature. METHODS: We retrospectively analysed lung 'organ offers' and LTx at our centre between January 2007 and November 2013. The outcomes of LTx utilizing lungs from donors with a history of cannabis smoking were compared with the outcomes of those with no such history using unadjusted model as well as propensity score matching. RESULTS: A total of 302 LTxs were performed during this period and were grouped depending on the history of cannabis smoking in donors-'cannabis' (n = 19) and control group (n = 283). All the donors in 'cannabis' group were tobacco smokers compared with 43% in the control group. Preoperative characteristics in recipients in both groups were comparable. Intraoperative and post-LTx variables including 1- and 3-year survivals were comparable in both groups. CONCLUSIONS: The history of donor cannabis smoking does not appear to affect early and mid-term outcomes after LTx and potentially improve the donor pool. As it does not seem to negatively affect the outcomes after LTx, it should not be per se considered a contraindication for lung donation.

Salvage myocardial revascularisation in spontaneous left main coronary artery dissection with cardiogenic shock - the role of mechanical circulatory support.

Spontaneous left main coronary artery dissection is a rare cause of acute coronary events or sudden cardiac death, constituting less than 1% of all epicardial coronary artery dissections. It is often fatal and is mostly recognized at post-mortem examination in young victims of sudden death. More than 70% of the reported cases occurred in women, particularly during pregnancy and the peripartum period and those on oral contraceptives. The clinical presentation is highly variable and prognosis varies widely, depending predominantly on the speed of diagnosis. Treatment options include medical therapy, revascularization with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) and mechanical circulatory support in cases of cardiogenic shock. We report a case of spontaneous dissection of the left main stem coronary artery, with extension into the left coronary territory, which occurred in a 41-year-old lady, complicated by profound cardiogenic shock requiring recovery with extracorporeal mechanical circulatory support after salvage myocardial revascularization.

Zonal organ allocation system and its impact on long-term outcomes after lung transplantation: a propensity score matched analysis†.

OBJECTIVE: Zonal organ allocation system comprises organ procurement by teams within a specific geographical area of each retrieval team. Therefore, in a substantial number of cases organs are retrieved by 'foreign' teams and are sent for transplantation to the implanting centre. The aim of this study was to assess the impact of zonal organ allocation system on early- and long-term outcomes after lung transplantation (LTx). METHODS: Included were 331 consecutive patients who underwent LTx performed at Harefield Hospital between January 2007 and January 2015. Recipients were divided into two groups depending on the organ retrieval team: 204 (61.6%) patients were transplanted using lungs procured by our institutional team (institutional group), whereas 127 (38.4%) organs were retrieved by other teams (external group) from experienced transplant centres in the UK. To exclude selection bias and other confounders, a 1:1 propensity score-based matching procedure was performed resulting in a total number of 238 donors and recipients who were well matched for baseline characteristics. The primary end-points were overall survival after LTx and freedom from bronchiolitis obliterans syndrome (BOS). Secondary end-points were perioperative clinical characteristics as well as adverse events that occurred over the follow-up. RESULT: After propensity score matching all donor characteristics and all baseline recipient characteristics were statistically similar between the two groups. In terms of early postoperative results, both groups were statistically comparable. However, there was a trend towards higher incidence of primary graft dysfunction in the external group (P = 0.054). Regarding long-term results with up to 7 years of follow-up, the overall survival also appeared to be poorer in the external group; however, this difference did not reach statistical significance. The freedom from BOS over the long-term follow was significantly poorer in the external group (P = 0.040). CONCLUSION: Despite excellent early outcomes the zonal allocation system might be associated with significantly poorer long-term outcomes in terms of freedom from BOS after bilateral LTx. Further research is needed to find the underlying factors leading to these results.

Contemporary review of the organ care system in lung transplantation: potential advantages of a portable ex-vivo lung perfusion system.

INTRODUCTION: Lung transplantation remains the definite treatment for various end-stage lung diseases. Cold flush perfusion, the standard method for organ procurement has severe limitations. Organ Care System (OCS; TransMedics, Inc., Andover, USA) is an approved method to preserve hearts for transplantation that allows for greatly reduced cold ischemic time. Consequently, the use of an adapted OCS lung as a portable full ex-vivo lung perfusion system in lung transplantation is currently under close evaluation. Areas covered: The aim of this article is to review the advantages and the role of the OCS in the field of lung transplantation by reviewing the latest literature and evaluating this novel procurement technique in the context of conventional methods like cold flush and regular ex-vivo lung perfusion. Expert commentary: The use of OCS in the field of lung transplantation has great potential for improved patients outcomes and is justified in cases with (i) marginal donor lungs, (ii) foreseeable long time of transportation (iii) high-risk recipient or donor /recipient profiles, particularly in the setting of an overall increasing need for suitable donor organs. Results from two major multi-centre prospective studies are pending to objectively assess the possible advantages of this portable ex-vivo lung perfusion system.

Utilization of the organ care system for bilateral lung transplantation: preliminary results of a comparative study.

OBJECTIVES: Lung transplantation (LTx) remains the gold standard for patients with end-stage lung disease. However, due to donor organ shortage and brain stem death-related lung injury, only a small proportion of lungs are used increasing the mortality rate on the waiting list. A portable normothermic continuous ex vivo perfusion using the organ care system (OCS) represents one of the tools to increase the pool of donor organs and to improve the function of marginal lungs. We sought to assess mid-term outcomes after LTx using OCS and to compare outcomes including overall survival and freedom from bronchiolitis obliterans syndrome (BOS) with those after conventional preservation. METHODS: Included were 322 consecutive LTx performed at Harefield Hospital between January 2007 and December 2014. Recipients were divided into two groups depending on the organ storage strategy: the majority of patients (n = 308) were transplanted using lungs after cold storage (cold storage group), whereas 14 organs were preserved using OCS (OCS group). The primary end-points were overall survival and freedom from BOS after LTx. The secondary end-points were perioperative clinical characteristics and adverse events. RESULTS: There were no statistically significant differences in terms of most baseline donor and recipient characteristics. The percentage of heavy smokers among donors [8 (2.9%) vs 6 (42.9%), P < 0.001] and the median number of pack-years smoked by donors [14 (7;24) vs 25 (24;30), P = 0.026] were statistically higher in the OCS group. Patients from the OCS group had significantly better postoperative FEV1 at 3 [69 (54;86) vs 93 (87;89), P < 0.001] and 6 [77 (60;90) vs 94 (84;100), P = 0.006] months. There were no statistically significant differences in terms of cumulative survival and freedom from BOS between the two groups. CONCLUSIONS: Results after LTx using OCS are acceptable with excellent survival, and superior early outcome in terms of postoperative lung function despite higher risk in the OCS group. Further larger prospective trials are warranted to confirm our preliminary results and to elaborate long-term outcomes.

Effect of donor cardiac arrest and arrest duration on outcomes of lung transplantation.

BACKGROUND: Limited data are available about lung transplantation (LTx) from donors suffering cardiac arrest (CA) prior to actual donation. METHODS: A retrospective analysis of LTx performed between January 2007 and September 2012 was done with the focus on CA in donors. The recipients were grouped depending on the history of donor CA and CA duration (downtime) as: No cardiac arrest ("NoCA"), CA downtime less than 20 min ("CA < 20"), and CA downtime equal to or more than 20 min ("CA > 20"). Early and mid-term outcomes after LTx were compared among the three groups. RESULTS: A total of 237 LTx were performed during the study period. One hundred eighty-eight patients received organs from "NoCA" donors, 25 from "CA < 20" donors, and 24 patients from "CA > 20" donors. There was a trend toward better overall cumulative survival in both CA groups (log rank p = 0.076) whereas the survival in the "CA > 20" group was significantly better than in the "NoCA" group in the subgroup analysis (log rank p = 0.045). Freedom from bronchiolitis obliterans syndrome (BOS) also increased with increase in CA duration, although it did not reach statistical significance. CONCLUSIONS: Transplantation of lungs from donors with a history of CA is safe and feasible. Longer duration of cardiac arrest may improve the outcomes after the LTx in terms of survival and freedom from BOS.

Outcomes of minimally invasive lung transplantation in a single centre: the routine approach for the future or do we still need clamshell incision?

OBJECTIVES: Minimally invasive lung transplantation (MILT) via bilateral anterior thoracotomies has emerged as a novel surgical strategy with potential patient benefits when compared with transverse thoracosternotomy (clamshell incision, CS). The aim of this study is to compare MILT with CS by focusing on operative characteristics, postoperative organ function and support and mid-term clinical outcomes at Harefield Hospital. METHODS: It was a retrospective observational study evaluating all bilateral sequential lung transplants between April 2010 and November 2013. RESULTS: CS was performed in 124 patients and MILT in 70 patients. Skin-to-skin surgical time was less in the MILT group [285 (265, 339) min] compared with CS [380 (306, 565) min] and MILT-cardiopulmonary bypass [426 (360, 478) min]. Ischaemic time was significantly longer (502 ± 116 vs 395 ± 145 min) in the MILT group compared with CS (P < 0.01). Early postoperative physiological variables were similar between groups. Patients in the MILT group required less blood [2 (0, 4) vs 3 (1, 5) units, P = 0.16] and platelet transfusion [0 (0, 1) vs 1 (0, 2) units, P < 0.01]. The median duration of mechanical ventilation was shorter (26 vs 44 h, P < 0.01) and intensive therapy unit stay was 2 days shorter (5 vs 7) in the MILT group. While overall survival was similar, fraction of expired volume in 1 s (FEV1) and forced vital capacity (FVC) were consistently higher in the MILT group compared with CS during mid-term follow-up after transplantation. Specifically, FEV1 and FVC were, respectively, 86 ± 21 and 88 ± 18% predicted in the MILT group compared with 74 ± 21 and 74 ± 19% predicted in the CS group (P < 0.01) at the 6-month follow-up. CONCLUSIONS: MILT was successfully introduced at our centre as a novel operative strategy. Despite longer ischaemic times and a more complex operation and management, MILT appears to offer early postoperative and mid-term clinical benefits compared with our traditional approach of clamshell operations. These observations warrant larger definite studies to further evaluate the impact of MILT on physiological, clinical and patient-reported outcomes.

Does postoperative blood pressure influence development of aortic regurgitation following continuous-flow left ventricular assist device implantation?†.

OBJECTIVES: The true impact of postoperative blood pressure (BP) control on development of aortic regurgitation (AR) following continuous-flow left ventricular assist device (CF-LVAD) implantation remains uncertain. This study examines the influence of BP in patients with de novo AR following CF-LVAD implantation. METHODS: All patients with no or

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.

Extracorporeal life support in patients with refractory cardiogenic shock: keep them awake.

OBJECTIVES: Traditionally, patients on extracorporeal life support (ECLS) are sedated and mechanically ventilated and therefore prone to complications related to immobility and ventilation. We adopted this 'Awake ECLS' strategy for the patients with refractory cardiogenic shock (RCS) as a bridge to decision. METHODS: Sixty-eight patients with RCS were supported by ECLS (All veno-arterial) in years 2010-2014. Patients that could not survive 24 h after ECLS implantation (9 patients) were excluded from the study. Study population constituted 59 patients-'Awake' group (n = 18; maintained awake without intubation) and 'Control' group (n = 41; intubated and required mechanical ventilation). RESULTS: Nine (50%) patients were awake at implantation, with 5 of them remaining free of sedation and ventilator support through to explantation. Nine patients were ventilated at the time of implantation but subsequently extubated and remained non-intubated and ventilator free. Post-ECLS survival at 1 month was 78 and 42% while the survival to discharge was 78 and 37% in awake and control group, respectively. CONCLUSIONS: ECLS as a bridge to decision in RCS is effective in restoring adequate systemic perfusion and recovering end-organ function. ECLS can be initiated in awake patients with RCS and patients can be awakened on ECLS. The 'awake ECLS' strategy may avoid complications related to mechanical ventilation, sedation and immobilization. RCS patients supported on ECLS without severe metabolic acidosis, multiorgan failure, intra-aortic balloon pump or uncertain neurological status are more likely to be weaned from the ventilator. Patients that are awake at the time of ECLS implantation are more likely to remain awake during ECLS.