Purpose Primary graft dysfunction (PGD) is the most common cause of early death in patients of heart transplantation (HTx) and the requirement of ECMO is one of the definitive criteria of PGD. The Organ Care System (OCS) offers ex-vivo donor heart perfusion and currently, the decision to use the OCS preserved donor heart for HTx depends upon the lactate trend and the ventricular contractility. We performed a metabolic analysis of the OCS perfusate samples to predict donor hearts that may develop PGD following HTx. Methods Between February 2013 and September 2019, 204 donor hearts procured from the donation after brain death was assessed using OCS. 53 hearts were declined for HTx based on lactate trend and ventricular contractility (No Tx); whereas in the remaining 152 hearts that were transplanted, 42 recipients required ECMO following HTx (Tx with ECMO) while 109 recipients did not require ECMO (Tx without ECMO). Results The proportion of unfavourable lactate trend and high 'end lactate' was significantly higher in the hearts declined for the HTx (no Tx group); however, there was no difference between 'Tx with ECMO' and 'Tx without ECMO' groups. The rate of fall of lactate was higher in the 'Tx without ECMO' compared to the 'Tx with ECMO'; however, did not reach statistical significance. Coronary blood flow was significantly low in the 'No Tx' group compared to the other two groups. O2 content, O2 delivery and O2 return were significantly low in the No Tx group and these markers were higher in 'Tx without ECMO' compared to 'Tx with ECMO', although not statistically significant. The diastolic pressure and the coronary vascular resistance fell after 30 minutes of OCS perfusion in the donor hearts that did not suffer PGD whereas it remained high in the donor hearts that suffered PGD. Conclusion The rate of fall of arterial lactate offered more valuable information compared to the overall lactate trend and end lactate in the prediction of PGD after HTx. Hearts declined for the HTx based on the unfavourable lactate trend, high-end lactate and suboptimal ventricular contractility are justified by the metabolic analysis that showed significantly low CaO2, DO2 and Oxygen return in the declined hearts. Hearts procured from donors after brain death and preserved with OCS that show consistently high coronary vascular resistance may develop PGD requiring ECMO.
Purpose Donation after circulatory death (DCD) is gaining momentum for heart transplantation worldwide. Central to the process is a detailed assessment of the donor heart following the circulatory arrest and unpredictable warm ischemia time. Our team used the Organ Care System as the principal means of assessment and preservation of the DCD hearts. Here we describe our single centre experience with DCD heart transplantation. Methods Between 2015 and 2021, 36 donor hearts were procured via the DCD pathway. Donor management involved the withdrawal of treatment (WoT) in the donor, stand-down time of 5 minutes following circulatory arrest (asystole), transfer of the patient to the operating theatre, collection of 1.2L donor blood from right atrium for Organ Care System (OCS) prime, delivery of cardioplegia and its procurement. The organs were assessed utilizing OCS and 25 suitable hearts that met the criteria of suitability were transplanted. Results The mean age of donors was 30.6±10.7 years (12% females) with intracranial haemorrhage and hypoxic brain damage as main causes of WoT. 52% of the donors suffered cardiac arrest before hospital admission, 25% had a history of cocaine abuse and 48% were current smokers. Mean WoT to asystole time was 11.8±4.1 min, mean WoT to cardioplegia time was 23.1±4.6 min and a mean functional warm ischemia time was 16.3±3.5 min. The mean OCS perfusion time was 245 ±81min.The mean recipient age was 42.6±13.2 years (12% females) with dilated (64%) and ischemic (24%) cardiomyopathy as an aetiology of heart failure in the majority. 6 (24%) patients had long term LVAD while 2(8%) were supported on short-term mechanical support per-operatively.9 (36%) patients required mechanical circulatory support postoperatively with ECMO and IABP and 20 (80%) required continuous renal replacement therapy. The mean ICU stay was 17.8±16.5 days and the mean hospital stay was 45±40 days. Postoperative survival at 30-days was 88%. Conclusion Donor hearts procured following donation after circulatory death were transplanted with acceptable short-term survival especially given the high proportion of preoperative mechanical circulatory support and urgency of transplantation in our cohort. 'Direct procurement and perfusion' method of procurement in DCD offers an opportunity to assess the donor heart for the suitability of transplantation.
The median incidence of Aspergillus infections in lung transplant recipients has been reported in up to 20%. The commonest site for infection is the tracheobronchial area, most commonly at the anastomotic site which is particularly vulnerable due to blood supply disruption to the donor airway and the presence of the sutures, a point of adhesion for pathogens. Bronchial anastomotic infections are a major risk factor for dehiscence, bronchial stenosis, fistulas and granulation tissue, with the potential of limiting the lung capacity and facilitate secretion retention. The treatment of bronchial anastomotic infections with triazoles is challenging due to the drug-drug interaction with CNIs and risk of liver toxicity. The use of systemic amphotericin B is usually avoided in lung transplant recipients due to the increased nephrotoxicity while the nebulised administration is often hindered by tolerability issues. Furthermore, the bronchial anastomosis remains quite ischemic post-transplantation, therefore the penetration at the site of infection of systemically administered antifungal agents is limited. The aim of this report is to describe our experience in using a potent, novel inhaled azole agent PC945 (Pulmocide) to treat a proven fungal bronchial anastomotic infection, refractory to systemic antifungal treatment. PC945 is designed to deliver high pulmonary concentrations with retention in cells offering a long duration of action and minimal systemic exposure. A 29-year-old woman who underwent a bilateral lung transplant in September 2018 for end stage cystic fibrosis developed an infection of the right main bronchial anastomosis four weeks after the transplant. Grocott staining on a biopsy of the affected bronchial mucosa highlighted fungal hyphae. Aspergillus fumigatus complex grew from a bronchoalveolar lavage sample.A treatment with isavuconazole and inhaled amphotericine B was started, switched to posaconazole and terbinafine due poor tolerance of the first two agents. A follow up bronchoscopy after six weeks of treatment showed worsening of the fungal ball attached to the sutures and endobronchial erythema. A treatment with nebulized PC945 5mg daily aqueous suspension was initiated under a special needs program. The patient reported excellent toleration with no adverse local nor systemic effects. Further follow up bronchoscopies showed progressive improvement with complete resolution of fungal ball and mucosal erythema after eight weeks of treatment. This is the first report of using PC945 as part of a combination treatment for a refractory fungal bronchial anastomotic infection and tracheobronchitis. It showed excellent tolerability profile and had promisingly proven effective in controlling the active infection.
Utilization of organs from high-risk donors may increase the number of orthotopic heart transplants (HTX), however, with possible detrimental effect on outcomes. Ex vivo normothermic preservation (EVNP) considerably reduces the cold ischemic time with potential benefit for post-transplant results when transplanting extended criteria grafts into high-risk recipients. In this study we analyze the midterm follow up results of HTx using extended criteria donor hearts following EVNP.
The onset of aortic regurgitation (AR) after left ventricular assist device (LVAD) implantation can affect device performance and patient outcomes. This single-centre study analyses the predictor factors for development of AR at long-term follow-up after implantation of LVADs.
Primary graft dysfunction (PGD) is a life threatening complication of heart transplantation (HTx). The incidence of PGD has been difficult to estimate due to the number of definitions applied to this term. PGD is common, affecting at least 20 % of heart transplant recipients and causes are multifactorial including donor, procedural and recipient factors. Veno-arterial extracorporeal membrane oxygenation (vaECMO) provides hemodynamic support in refractory cardiogenic shock and may be used after HTx for PGD or rejection.1
It remains controversial whether preoperative renal dysfunction affects mortality after prolonged LVAD support as long term follow up studies are limited to 1 year. The purpose was to investigate changes in estimated glomerular filtration rate (eGFR) up to 8 years post LVAD implant and their impact on long term survival.
Vocal cord paralysis (VCP) is a known complication following cardiothoracic surgery and can lead to dysphonia, shortness of breath, ineffective cough and aspiration. Few studies have reported the incidence of VCP and associated dysphagia following VAD implantation. The purpose of this study is to evaluate the incidence of VCP and presence of aspiration in this cohort.
Purpose: Everolimus is a proliferation signal inhibitor used for triple immunosuppressive therapy following solid organ transplantation. Its positive benefits, such as reduction of acute rejection episodes and reduced nephrotoxicity have been shown in kidney-as well as heart transplantation. However the role of everolimus is less well defined in lung transplantation. We thus wished to study the effect of primary immunosuppression with everolimus in a preclinical large animal lung transplantation model. Methods: Left-sided single lung transplantation from MHC-mismatched donors was performed in 11 adult minipigs. Intravenous pharmacologic immunosuppression was maintained for 28 days with 1.5 mg/kg/d methylprednisolone, 1.0 mg/kg/d azathioprine and cyclosporine A (blood levels 300-500 ng/ml; CsA group; n = 5). A further group (CsA + Ev; n = 6) received methylprednisolone, CsA (200-300 ng/ml) and Everolimus (5-10 ng/ml). Immunosuppression was discontinued on postoperative day (POD) 28. Graft survival was monitored by sequential chest X-rays, bronchoscopies and transbronchial biopsy histology. Results: All animals survived the 28 day course of immunosuppressive therapy and showed healthy grafts on POD 28. Median allograft survival in the CsA group was 55 +/- 15 days. CsA + Ev grafts showed median survival of 49 +/- 86 days (p = 0.37). Conclusion: Whereas everolimus might be advantageous as maintenance immunosuppressive agent, this data does not support an important role for everolimus in the immunosuppressive induction phase following lung transplantation.
Patients presenting with biventricular heart failure are generally sicker than those with left ventricular heart failure, and they have fewer options outside of cardiac transplantation. The small size of the HeartWare HVADTM has led surgeons to implant two pumps in a biventricular assist device (BiVAD) configuration. The rationale of using two HVADs as BiVAD is its small size and light-weight external components, permitting ambulation and home discharge. However, the HVAD was designed to be used as a left ventricular assist system (LVAD). Various adaptations have been described to deploy the HVAD for right ventricular support.
Frailty is associated with worse survival post lung transplantation than non-frail patients (Wilson et al. 2016). Recognition of these patients at assessment may help decision making regarding listing and target interventions to ameliorate frailty. Currently, the six-minute walk test (6MWT) is the gold standard for physical performance in lung transplantation assessment. The Short Physical Performance Battery (SPPB) is a well validated frailty measure with an emphasis on physical function. The aim of the study was to determine whether the SPPB correlates to six-minute walk distance (6MWD).
Spirometry is gold standard for detecting chronic lung allograft (CLAD) dysfunction. Peak cough flow (PCF) assesses cough strength and identifies those at risk of developing respiratory tract infections, which contribute to the development of CLAD. Normal adult PCF 440-1200 L/min, ≥ 270 L/min PCF demonstrates adequate cough, ≤ 160 L/min demonstrates inefficient cough. Study Aims: 1. To evaluate the feasibility of recruitment and PCF testing alongside standard care 2. To examine the relationship between PCF and forced vital capacity (FVC) and PCF and forced expiratory volume in one second (FEV1), and the factors that influence this post bilateral sequential single lung transplant (BSSLTx).
Computed tomography coronary angiography (CTCA) has been established as an alternative to invasive angiography to detect cardiac allograft vasculopathy (CAV). However, the prognostic significance of CTCA in this patient cohort has not been established.
Cardiac transplantation (HTx) is the “gold-standard” treatment for eligible patients with advanced heart failure, but it has become limited by a critical shortage of suitable organs from brain-dead donors (DBD) (1). Donation after circulatory death (DCD) describes the procurement of organs from donors that have been declared dead based on circulatory criteria. As the main concern of DCD hearts is in the possible myocardial injury due to the ischemic time from withdrawal of life sustaining therapies until the heart is either perfused in situ or until cardioplegia is delivered. Ex vivo normothermic preservation (EVNP) considerably reduces the cold ischemic time with potential benefit for post-transplant results.
Lung transplantation has significant early mortality, mainly related to primary graft dysfunction and infectious complications [ [1] Lund L.H. Khush K.K. Cherikh W.S. Goldfarb S. Kucheryavaya A.Y. Levvey B.J. et al. International Society for Heart and Lung TransplantationThe Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Heart Transplantation Report-2017; Focus Theme: Allograft ischemic time.. J Heart Lung Transplant. 2017; 36: 1037-1046 Abstract Full Text Full Text PDF PubMed Scopus (491) Google Scholar ]. The most frequent infections are catheter-related bloodstream infections and pneumonia [ [2] Ji Hyun Y. Sang-Oh L. Kyung-Wook J. Se Hoon C. Jina L. Eun Jin C. Infections after lung transplantation: time of occurrence, sites, and microbiologic etiologies. Korean J Intern Med. 2015; 30: 506-514 Crossref PubMed Scopus (27) Google Scholar ]. We report what we believe to be the first ever described case of infection with Elisabethkingia miricola in a patient after lung transplantation.
DCD LTx became a significant part of transplant activity over the last decade. Initial reports showed excellent short and mid-term results but there is a limited data about long-term outcome available. In this paper we evaluate our results in a large single center cohort with long observation period.
Anticoagulation management in patients with Left Ventricular Assist devices (LVAD) continues to be a challenge. Patients and their clinicians are faced with the daily challenge of needing adequate anticoagulation versus the bleeding risks that are associated with anticoagulation.Warfarin is the recommended oral anticoagulant for all currently available LVAD devices.Warfarin is known to be a difficult medication to manage due to its narrow therapeutic window, and its many interactions .Dlott et al (2014) describe in Circulation the overall time in therapeutic range for patients on warfarin as 53.7%, Time in therapeutic range has been corelated with stroke, bleeding and mortality rates.The goal of our team was to maximise the time patients with VAD's spent in their therapeutic INR range.
Die Lungentransplantation hat einen souveränen Stellenwert in der Therapie schwerer therapierefraktärer Lungenerkrankungen. Obwohl chirurgische Technik und perioperative Versorgung hochstandardisiert erscheinen, wird der Einsatz extrakorporaler Verfahren (extrakorporale Zirkulation, EKZ) während der Transplantation hinsichtlich des Risiko-Nutzen-Verhältnisses kontrovers diskutiert.
Recently, following donation after circulatory death (DCD), it has been demonstrated that adult hearts can be transplanted into low-risk recipients using normothermic reperfusion. Here we show this is also feasible in spite of an adverse donor/recipient risk profile.