Michiel E. Erasmus

Influence of age on survival, late hypertension, and recoarctation in elective aortic coarctation repair. Including long-term results after elective aortic coarctation repair with a follow-up from 25 to 44 years.

The optimal age for elective repair of aortic coarctation is controversial. The optimal age should be associated with a minimal risk of recoarctation, late hypertension, and other cardiovascular disorders. The purpose of this retrospective study is to determine the actuarial survival after aortic coarctation repair 25 years or more after operation and to calculate the optimal age for elective aortic coarctation repair. From 1948 to 1966, 120 consecutive patients underwent aortic coarctation repair. Eighty-seven were male (72.5%). The mean age at operation was 15.5 years (SD +/- 9.1 years). Resection and end-to-end anastomosis was performed in 103 patients (85.8%). Early mortality occurred in 6 patients as a result of surgical problems, whereas late mortality in 15 patients was predominantly caused by cardiac causes. The mean follow-up period was 32 years (range 25 to 44.2 years). Ninety-two patients 96.8%) were in New York Heart Association class I. The probability of survival 44 years after operation was 73%. Patients younger than 10 years at operation had the highest probability of survival at 97%. Multivariate analysis produced age at operation as the only incremental risk factor for the occurrence of recoarctation, of late hypertension, and of premature death. So that these sequelae can be avoided, elective aortic coarctation repair should be performed around 1.5 years of age. At that age, the probability of recoarctation will have decreased to less than 3%, and the probability of upper body normotension and long-term survival will be optimal.

Epstein-Barr virus-DNA load monitoring late after lung transplantation: A surrogate marker of the degree of immunosuppression and a safe guide to reduce immunosuppression

Background. Posttransplant lymphoproliferative disease (PTLD) is a serious complication after lung transplantation and its relation with Epstein-Barr virus (EBV) is well recognized. It has been postulated that preemptive reduction of immunosuppression guided by EBV-DNA load may lead to a significantly lower incidence of PTLD, because of the reconstitution of T-cell control. In this report, we describe the feasibility of this approach in terms of safety with regard to the risk of acute as well as chronic allograft rejection in 75 lung transplant recipients transplanted between 1990 and 2001 and followed for this study from June 1, 2001 until January 1, 2006. Methods. From all patients visiting our outpatient clinic, EBV-DNA load was measured at least twice a year during the study period. In patients with positive results, measurements were repeated every two to four weeks. EBV reactivation was defined as two consecutive EBV-DNA load measurements with a rising trend; with the last measurement exceeding 10.000 copies/mL under stable immunosuppression. In such case, immunosuppression was reduced. Results. EBV reactivation was observed in 26/75 patients (35%). One (1.5%) of these patients developed PTLD during the study period. Acute rejection, acceleration of chronic allograft rejection, or worse survival were not observed after reduction of immunosuppression. Conclusions. Preemptive reduction of immunosuppression after lung transplantation guided by EBV-DNA load appears to be a safe approach for the prevention of PTLD in lung transplant recipients late after transplantation.

Chronic ischaemic mitral regurgitation. Current treatment results and new mechanism-based surgical approaches

Chronic ischaemic mitral regurgitation (CIMR) remains one of the most complex and unresolved aspects in the management of ischaemic heart disease. This review provides an overview of the present knowledge about the different aspects of CIMR with an emphasis on mechanisms, current surgical treatment results and new mechanism-based surgical approaches. CIMR occurs in approximately 20-25% of patients followed up after myocardial infarction (MI) and in 50% of those with post-infarct congestive heart failure (CHF). The presence of CIMR adversely affects prognosis, increasing mortality and the risk of CHF in a graded fashion according to CIMR severity. The primary mechanism of CIMR is ischaemia-induced left ventricular (LV) remodelling with papillary muscle displacement and apical tenting of the mitral valve leaflets. CIMR is often clinically silent, and colour-Doppler echocardiography remains the most reliable diagnostic tool. The most commonly performed surgical procedure for CIMR (restrictive annuloplasty combined with coronary artery bypass grafting (CABG)) can provide good results in selected patients with minimal LV dilatation and minimal tenting. However, in general the persistence and recurrence rate (at least MR grade 3+) for restrictive annuloplasty remains high (up to 30% at 6 months postoperatively), and after a 10-year follow-up there does not appear to be a survival benefit of a combined procedure compared to CABG alone (10-year survival rate for both is approximately 50%). Patients at risk of annuloplasty failure based on preoperative echocardiographic and clinical parameters may benefit from mitral valve replacement with preservation of the subvalvular apparatus or from new alternative procedures targeting the subvalvular apparatus including the LV. These new procedures include second-order chordal cutting, papillary muscle repositioning by a variety of techniques and ventricular approaches using external ventricular restraint devices or the Coapsys device. In addition, percutaneous transvenous repair techniques are being developed. Although promising, at this point these new procedures still lack investigation in large patient cohorts with long-term follow-up. They will, however, be the subject of much anticipated and necessary ongoing and future research.

Normothermic ex vivo lung perfusion of non-heart-beating donor lungs in pigs: from pretransplant function analysis towards a 6-h machine preservation

Donor shortage urges optimal use of all lungs available. Ex vivo lung perfusion (EVLP) is a method to evaluate lung function before implantation. EVLP was performed in pigs to evaluate lung function, using two different clinical non‐heart‐beating (NHS) donor protocols: flush perfusion and topical cooling after 1‐h warm ischaemia (n = 5 each). Secondly, we investigated whether EVLP can be used for 6 h ex vivo machine preservation (n = 4). In comparison with topical cooling, flush perfusion preserved lung function better during EVLP. During 6 h normothermic EVLP, gas exchange remained stable; however, the pulmonary artery pressure and ventilation pressure showed a significant increase. EVLP is a reliable method for evaluation of lung graft function. Flush perfusion with Perfadex is preferred above topical cooling in NHB lung donation. Six‐hour normothermic EVLP is feasible but should be further improved to make ex vivo machine preservation or treatment of lung grafts successful.

Lung Transplantation from Nonheparinized Category III Non-Heart-Beating Donors. A Single-Centre Report

Background. Despite the increasing use of extended lung donors, the shortage of lung donors remains. Usage of non-heart-beating (NHB) lung donors contributes to fight this shortage. We describe our experience in 21 consecutive adult lung transplantations using nonheparinized category III NHB donors and standard flush preservation. Methods. From January 2005 to December 2008, we collected donor and recipient data of all NHB category III lung transplantations performed in our center. For comparison, we also collected the data of all heart-beating (HB) lung transplantations in the same period. We focused on data describing the donor, the donor procedure, the recipients primary graft dysfunction, survival, rejection episodes, and the lung graft function. Results. Twenty-one NHB and 77 HB lung transplantations were performed. Circulation arrest occurred after 14 (4–62) min and warm ischemia time was 30 (19–44) min. Occurrence of primary graft dysfunction, acute rejection episodes, development of bronchiolitis obliterans syndrome was equal to the HB cohort as was the 2 years survival of 95% in the NHB group compared with 86% in the HB group. Lung graft function during the first 2 years tended to be better preserved in the NHB group. Conclusion. Category III NHB lung donation is a good alternative in addition to HB lung donation. Using nonheparinized category III NHB donors and standard ante- and retrograde, flush perfusion resulted in good lung graft function and survival. NHB donation offers a great opportunity to reduce the burden of donor lung shortage.

International Society for Heart and Lung Transplantation Donation After Circulatory Death Registry Report

BACKGROUND The objective of this study was to review the international experience in lung transplantation using lung donation after circulatory death (DCD). METHODS In this retrospective study, data from the International Society for Heart and Lung Transplantation (ISHLT) DCD Registry were analyzed. The study cohort included DCD lung transplants performed between January 2003 and June 2013, and reported to the ISHLT DCD Registry as of April 2014. The participating institutions included 10 centers in North America, Europe and Australia. The control group was a cohort of lung recipients transplanted using brain-dead donors (DBDs) during the same study period. The primary end-point was survival after lung transplantation. RESULTS There were 306 transplants performed using DCD donors and 3,992 transplants using DBD donors during the study period. Of the DCD transplants, 94.8% were Maastricht Category III, whereas 4% were Category IV and 1.2% Category V (euthanasia). Heparin was given in 54% of the cases, donor extubation occurred in 90% of the cases, and normothermic ex vivo lung perfusion (EVLP) was used in 12%. The median time from withdrawal of life support therapy (WLST) to cardiac arrest was 15 minutes (5th to 95th percentiles of 5 to 55 minutes), and from WLST to cold flush was 33 minutes (5th to 95th percentiles of 19.5 to 79.5 minutes). Recipient age and medical diagnosis were similar in DCD and DBD groups (p = not significant [NS]). Median hospital length of stay was 18 days in DCD lung transplants and 16 days in DBD transplants (p = 0.016). Thirty-day survival was 96% in the DCD group and 97% in the DBD group. One-year survival was 89% in the DCD group and 88% in the DBD group (p = NS). Five-year survival was 61% in both groups (p = NS). The mechanism of donor death within the DCD group seemed to influence recipient early survival. The survival rates through 30 days were significantly different by donor mechanism of death (p = 0.0152). There was no significant correlation between the interval of WLST to pulmonary flush with survival (p = 0.11). CONCLUSION This large study of international, multi-center experience demonstrates excellent survival after lung transplantation using DCD donors. It should be further evaluated whether the mechanism of donor death influences survival after DCD transplant.

The use of non-heart-beating lung donors category III can increase the donor pool

OBJECTIVE The use of non-heart-beating (NHB) lung donors has been propagated as an alternative besides heart-beating (HB) lung donors to overcome organ shortage. We evaluated the effectiveness of NHB lung transplantation. METHODS The donor and recipient data of all 35 NHB category III lung transplantations (LTx) between January 2005 and December 2009 were reviewed. For comparison, we collected recipient and donor data of a cohort of 77 HB lung transplantations. In both groups, we assessed survival, primary graft dysfunction (PGD), forced expiratory volume in 1s (FEV(1)), acute rejection, and bronchiolitis obliterans syndrome (BOS). RESULTS Thirty-five NHB lung transplantations were performed, five single LTx and 30 bilateral LTx in 12 male and 23 female patients. The donor oxygenation capacity was 61 kPa (interquartile range (IQR), 56-64). Warm ischemia time in the donor was 29 min (IQR, 24-30). Cold ischemic time of the last implanted lung was 458 min (IQR, 392-522). Cardiopulmonary bypass was used 13 times. PGD (1-3) was observed in 45% of the patients at T0, in 42% at T24, in 53% at T48, and in 50% at T72. PGD 3 decreased from 24% at T0 to 6% at T72. The use of nitric oxide (NO) within 24h after transplantation was necessary in three patients with successful weaning in all. There was no significant difference for donor and recipient characteristics between NHB and HB lung transplantations. Survival, occurrence of PGD, and acute rejection was equal to the HB cohort. The incidence of BOS was lower in the NHB group. The measured FEV(1) tended to be better in the NHB group. CONCLUSION Lungs from nonheparinized category III NHB donors are well suited for transplantation and can safely increase the donor pool.

The effect of bronchiolitis obliterans syndrome on health related quality of life

Abstract:  Bronchiolitis obliterans syndrome (BOS) is the most important factor limiting long‐term survival after lung transplantation, and has a substantial impact on patients‘ daily life in terms of disability and morbidity. Aim of our study was to examine the effects of BOS on health related quality of life (HRQL) in lung transplantation patients. Data on HRQL from 29 patients who developed BOS at least 18 months earlier were studied longitudinally. HRQL measures were: the Nottingham Health Profile (NHP), the State Trait Anxiety Inventory (STAI), the Self‐rating Depression Scale (ZUNG), and the Index of Well Being (IWB). Furthermore questions concerning activities of daily life and dyspnea were asked. The majority of the patients were male, and the most common diagnosis was emphysema. After the onset of BOS, significantly more restrictions were reported on the dimensions energy and mobility of the NHP. These restrictions appeared to increase over time. After the onset of BOS, STAI scores remained more or less stable and close to the value of the general population. ZUNG scores were significantly higher after the onset of BOS, and patients experienced a lower level of well being than the general population. The percentage of patients that reported to be able to perform activities of daily life without effort declined dramatically after the onset of BOS. Furthermore, the percentage of patients complaining of dyspnea increased after the onset of BOS. In conclusion, our study showed that HRQL was negatively affected by the onset of BOS. However, in spite of these less favorable long‐term results, even patients who develop BOS may at least temporarily benefit from a lung transplantation.

Mitral valve surgery for mitral regurgitation caused by Libman-Sacks endocarditis: a report of four cases and a systematic review of the literature

Libman-Sacks endocarditis of the mitral valve was first described by Libman and Sacks in 1924. Currently, the sterile verrucous vegetative lesions seen in Libman-Sacks endocarditis are regarded as a cardiac manifestation of both systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). Although typically mild and asymptomatic, complications of Libman-Sacks endocarditis may include superimposed bacterial endocarditis, thromboembolic events, and severe valvular regurgitation and/or stenosis requiring surgery. In this study we report two cases of mitral valve repair and two cases of mitral valve replacement for mitral regurgitation (MR) caused by Libman-Sacks endocarditis. In addition, we provide a systematic review of the English literature on mitral valve surgery for MR caused by Libman-Sacks endocarditis. This report shows that mitral valve repair is feasible and effective in young patients with relatively stable SLE and/or APS and only localized mitral valve abnormalities caused by Libman-Sacks endocarditis. Both clinical and echocardiographic follow-up after repair show excellent mid- and long-term results.

Lung Transplantation for Ventilator-Dependent Respiratory Failure

INTRODUCTION Lung transplantation of patients on mechanical ventilation is controversial, but successful transplantation of these patients has been reported. This report describes our institutional experience with lung transplantation of mechanically ventilated patients since 2003. METHODS A retrospective cohort study was performed of all adult patients who underwent transplantation between October 2003 and October 2007. The patients on mechanical ventilation before transplantation were compared with patients without mechanical ventilation before transplantation. Survival, intensive care unit and hospital length of stay, post-transplant mechanical ventilation days, and primary graft function were analyzed. RESULTS Before transplantation, 15 patients received mechanical ventilation for a median of 20 days (range, 5-90 days); of these, 13 underwent transplantation, and 2 died waiting for transplantation. The control group comprised 70 patients. Time on the transplantation waiting list was significantly shorter for the study group vs the control group. The 2 groups did not differ in survival, post-transplantation hospital time, and primary graft dysfunction scores at 0, 24, 48 and 72 hours after transplantation. Median time of mechanical ventilation after transplantation and median length of stay in the intensive care unit stay were longer in the study group. CONCLUSION The survival rate and post-operative clinical course of patients undergoing transplantation while receiving mechanical ventilation for respiratory failure suggest that these patients can be considered for lung transplantation. Despite a longer time on post-operative mechanical ventilation and length of ICU stay, outcome is similar to that of other lung transplant candidates.