A. Ardehali

Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial

BACKGROUNDnThe Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation.nnnMETHODSnWe did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712.nnnFINDINGSnBetween June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events.nnnINTERPRETATIONnHeart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study.nnnFUNDINGnTransMedics.

Mycobacterium abscessus empyema in a lung transplant recipient

Non-tuberculous mycobacteria (NTM) have emerged as important pathogens in organ transplant recipients. Because NTM pulmonary infections vary in their clinical and radiographic presentations, heightened clinical suspicion is necessary for accurate diagnosis. We report a case of Mycobacterium abscessus empyema in a lung transplant recipient. Repeated attempts at identifying the organism from a variety of clinical specimens led to the correct diagnosis and treatment.

Modification of the Fontan Procedure Superior Vena Cava to Left Pulmonary Artery Connection and Inferior Vena Cava to Right Pulmonary Artery Connection With Adjustable Atrial Septal Defect

BACKGROUNDnA modification of the Fontan procedure with unidirectional cavopulmonary connection is described in which the superior vena cava (SVC) is connected to the left pulmonary artery (PA) and the inferior vena cava (IVC) is connected to the right PA via a lateral tunnel with a snare-controlled, adjustable atrial septal defect (ASD). This allows matching of the SVC and IVC flows with the lung of appropriate size. The obligatory left Glenn shunt provides an adequate arterial oxygen saturation, and the elevation in SVC pressure is well tolerated. The adjustable ASD allows selective decompression of the IVC that maintains cardiac output and reduces fluid accumulation in the serous cavities.nnnMETHODS AND RESULTSnSince March 1992, we have performed this procedure in 18 patients. There were 17 children and 1 adult. Median age was 3 years and 9 months (range, 13 months to 36 years). Six patients had been staged with a previous bidirectional Glenn shunt. Preoperative cardiac catheterization revealed a PA pressure of 13 +/- 2 mm Hg and a transpulmonary gradient of 5 +/- 3 mm Hg. Ventricular function was satisfactory in all patients. At the completion of bypass, the pressures in the SVC and IVC were 16 +/- 4 mm Hg and 10 +/- 3 mm Hg, respectively (P < .01). The left atrial pressure was 6.0 +/- 3.0 mm Hg and the arterial O2 saturation on 100% oxygen was 93 +/- 3%. There was one death as a result of intractable atrial arrhythmias. The remaining 17 patients had a mean hospital stay of 9.7 days (6 to 18 days). The length of pleural drainage was 7 +/- 3 days. The ASD was adjusted in 11 patients before discharge. Oxygen saturation at discharge was 85.4 +/- 4%. Nine patients had repeat catheterization. The ASD was completely closed in 6 patients, an average of 2.5 months after surgery (range, 3 weeks to 5 months). After ASD closure, the arterial oxygen saturation was 96 +/- 3%, and the SVC and IVC pressures were both 13 +/- 3 mm Hg.nnnCONCLUSIONSnThe Fontan procedure with unidirectional cavopulmonary connection and adjustable ASD has several advantages that may reduce mortality and morbidity for the high-risk Fontan candidate.

Gene therapy and heart transplantation

The application of gene transfer technologies to the field of solid organ transplantation is uniquely appealing due to open access to the donor organ at the time of removal and the need for a local biological effect limited to the allograft. The objectives of gene transfer technology in the field of experimental heart transplantation include: firstly, modification of allograft phenotype and secondly, modulation of the host alloimmune response. Both objectives can theoretically decrease or eliminate the need for lifelong immunosuppression with its attendant risks. This article will review the principles and current methodology of gene transfer technology, applications of gene transfer technology to allo- and xeno- transplantation and the current status of clinical trials on gene therapy.

Bronchiolitis obliterans with organizing pneumonia: possible association with human herpes virus-7 infection after lung transplantation

transplant database of the centre was carried out. All single lung (SL), double lung (DL) and heart-lung block (HL) transplant patients who survived over 2 years post transplant were included in the study group. They were grouped as follows: A 5 D-/R(n5102), B 5 D-/R1 (n570), C 5 D1/R(n533) and E 5 D1/R1 (n592). The respective incidence of BOS in the different groups was 43.1%, 45.7%, 51.5% and 47.8% (p50.32). The 3-year BOS free survival was 65%, 56%, 58% and 67% respectively (p.0.05). In group A, the significant risk factors for developing BOS were three or more episodes of acute rejection (p50.02) and non-CMV pulmonary infection (p50.03). The mean number of acute rejection episodes per 100 patients days within the first six months were 1.28 (group A), 1.06 (group B), 0.50 (group C) and 1.11 (group E) [p,0.05]. Conclusion: Although CMV has been shown to be a risk factor for BOS, its absence did not preclude lung transplant patients from developing BOS. Moreover, absence of CMV was associated with an increase in the number of acute rejection episodes within the first transplant year. However, this could be accounted for by changes in frequency of acute rejection over time. Moreover, this may also reflect the non-uniformity of the pathological processes that are grouped as BOS.

A Comparison of Distribution Between Simultaneously or Sequentially Delivered Antegrade/Retrograde Blood Cardioplegia

Abstract Commercially available cardioplegia delivery systems now allow for antegrade (aortic root, coronary ostia, saphenous vein graft) perfusion to occur either sequentially or simultaneous with retrograde (coronary sinus) perfusion. This study was designed to compare the total flow and local distribution of sequential versus simultaneous antegrade/retrograde cardioplegia delivery. Methods: Explanted human hearts diagnosed with idiopathic cardiomyopathy underwent a cold cardioplegic arrest and bicaval cardiectomy. Thirty‐seven degree centigrade blood cardioplegia containing colored microspheres was then delivered antegrade (red color) at a pressure of 80 mmHg or retrograde (blue color) at a pressure of 40 mmHg. In the sequential group (n = 6), cardioplegia was delivered antegrade and then retrograde for 2 minutes, respectively. For the simultaneous group (n = 6), cardioplegia was delivered both antegrade and retrograde for 2 minutes. The ventricular myocardium was then sampled at 12 representative sites to determine regional cardioplegic flow. Results: Mean total cardioplegia delivery/minute was 0.69 ± 0.62 mL/g per minute for sequential cardioplegia, and 0.46 ± 0.19 mL/g per minute for simultaneous cardioplegia (p > 0.05, NS). At the 12 ventricular sites sampled, mean regional cardioplegic flow (mL/g per min) was in general slightly greater for sequential delivery. However, this was not statistically significant (p > 0.05, NS). Conclusion: The data suggest that there may be a slight advantage in total cardioplegia delivery and regional cardioplegia delivery when using sequential rather than simultaneous cardioplegia delivery. However, this difference was not statistically significant and is likely not of clinical significance. Therefore, we would recommend using either sequential or simultaneous antegrade/retrograde cardioplegia based upon whichever technique facilitates the conduct of the individual operation.

Lung transplantation in the Lung Allocation Score era: Medium-term analysis from a single center

In 2005, the Lung Allocation Score (LAS) was implemented as the allocation system for lungs in the US. We sought to compare 5‐year lung transplant outcomes before and after the institution of the LAS. Between 2000 and 2011, 501 adult patients were identified, with 132 from January 2000 to April 2005 (Pre‐LAS era) and 369 from May 2005 to December 2011 (Post‐LAS era). Kruskal‐Wallis or chi‐squared test was used to determine significance between groups. Survival was censored at 5 years. Overall, the post‐LAS era was associated with more restrictive lung disease, higher LAS scores, shorter wait‐list times, more preoperative immunosuppression, and more single lung transplantation. In addition, post‐LAS patients had higher O2 requirements with greater preoperative pulmonary impairment. Postoperatively, 30‐day mortality improved in post‐LAS era (1.6% vs 5.3%, P = .048). During the pre‐ and post‐LAS eras, 5‐year survival was 52.3% and 55.3%, respectively (P = .414). The adjusted risk of mortality was not different in the post‐LAS era (P = .139). Freedom from chronic lung allograft dysfunction was significantly higher in the post‐LAS era (P = .002). In this single‐center report, implementation of the LAS score has led to allocation to sicker patients without decrement in short‐ or medium‐term outcomes. Freedom from CLAD at 5 years is improving after LAS implementation.