Effects of the duration of bridge to lung transplantation with extracorporeal membrane oxygenation.

BACKGROUND: Although bridge to lung transplantation (BTT) with extracorporeal membrane oxygenation (ECMO) is increasingly performed, the impact of BTT and its duration on post-transplant outcomes are unclear. METHODS: We retrospectively reviewed medical records of adult patients who underwent lung or heart-lung transplantation in our institution between January 2008 and December 2018. Data were compared in patients who did (n = 41; BTT) and did not (n = 36; non-BTT) require pre-transplant ECMO support. Data were also compared in patients who underwent short-term (<14 days; n = 21; ST-BTT) and long-term (≥14 days; n = 20; LT-BTT) BTTs. RESULTS: Among 77 patients included, 51 (66.2%) were male and median age was 53 years. The median bridging time in the BTT group was 13 days (interquartile range [IQR], 7-19 days). Although simplified acute physiologic score II was significantly higher in the BTT group (median, 35; IQR, 31-49 in BTT group vs. median, 12; IQR, 7-19 in non-BTT group; p<0.001), 1-year (73.2% vs. 80.6%; p = 0.361) and 5-year (61.5% vs. 61.5%; p = 0.765) post-transplant survival rates were comparable in both groups. Comparison of ST- and LT-BTT subgroups showed that 1-year (90.5% vs. 55.0%; p = 0.009) and 5-year (73.0% vs. 48.1%; p = 0.030) post-transplant survival rates were significantly higher in ST-BTT group. In age and sex adjusted model, the LT-BTT was an independent risk factor for 1-year post-transplant mortality (hazard ratio, 3.019; 95% confidence interval, 1.119-8.146; p = 0.029), whereas the ST-BTT was not. CONCLUSIONS: Despite the severe illness, the BTT group showed favorable post-transplantation outcomes, particularly those bridged for less than 14 days.

Operating room extubation: A predictive factor for 1-year survival after double-lung transplantation.

BACKGROUND: Operating room (OR) extubation has been reported after lung transplantation (LT) in small cohorts. This study aimed to evaluate the prognosis of OR-extubated patients. The secondary objectives were to evaluate the safety of this approach and to identify its predictive factors. METHODS: This retrospective single-center cohort study included patients undergoing double lung transplantation (DLT) from January 2012 to June 2019. Patients undergoing multiorgan transplantation, repeat transplantation, or cardiopulmonary bypass during the study period were excluded. OR-extubated patients were compared with intensive care unit (ICU)-extubated patients. RESULTS: Among the 450 patients included in the analysis, 161 (35.8%) were extubated in the OR, and 4 were reintubated within 24 hours. Predictive factors for OR extubation were chronic obstructive pulmonary disease (COPD)/emphysema (p = .002) and cystic fibrosis (p = .005), recipient body mass index (p = .048), and the PaO2/FiO2 ratio 10 minutes after second graft implantation (p < .001). OR-extubated patients had a lower prevalence of grade 3 primary graft dysfunction at day 3 (p < .001). Eight (5.0%) patients died within the first year after OR extubation, and 49 (13.5%) patients died after ICU extubation (log-rank test; p = .005). After adjustment for OR extubation predictive factors, the multivariate Cox regression model showed that OR extubation was associated with greater one-year survival (adjusted hazard ratio = 0.40 [0.16-0.91], p = .028). CONCLUSIONS: OR extubation was associated with a favorable prognosis after DLT, but the association should not be interpreted as causality. This fast-track protocol was made possible by a team committed to developing a comprehensive strategy to enhance recovery.

Pediatric heart-lung transplantation: A contemporary analysis of outcomes.

BACKGROUND: Pediatric heart-lung transplantation (HLT) is rare, and no report has analyzed patient outcomes since time of listing. We analyzed pediatric HLTs to understand risk factors for waitlist and post-HLT mortality. METHODS: All pediatric (<18 year old) HLT candidates were identified within the UNOS database (n = 573) and grouped by age, era, and by diagnosis. Logistical regression and Cox proportional hazard modeling identified risk factors for 6-month WL and overall post-transplant mortality. RESULTS: 209/573 (37%) HLT candidates were transplanted, 7% recovered, 42% died waiting, and 15% were removed for another/unknown reason. Diagnoses were primary pulmonary hypertension(n = 130), congenital heart disease(CHD) without Eisenmenger's syndrome (ES) (n = 65), CHD with ES (n = 73), and other (n = 305). Patients with a diagnosis other than CHD with ES (OR: 7.55, P = .001), on IV inotropic support (OR: 2.79, P < .001), and infants (OR: 2.20, P = .004) were associated with waitlist mortality. There has been a 56% reduction in HLTs across eras (Era 1:10.8/yr vs Era 2:4.7/yr). Risk factors for post-transplant mortality were ECMO (HR: 4.1, P = .016), and being infant (HR: 2.2, P = .04) or 1-11 years old (HR: 1.78, P = .015). ECMO patients have an 87% 2-year mortality rate with a median post-transplant survival of 64 days. Overall, post-transplant survival was unchanged (log-rank P = .067) between eras. Excluding ECMO patients, in the recent era 29 non-infant patients with primary pulmonary hypertension had 93% 1-year survival and 67% 5-year survival. CONCLUSIONS: Nearly 600 pediatric patients have been listed for HLT in UNOS, although numbers are decreasing in the current era. HLT for a patient on ECMO appears to be an ineffective strategy; however, in well-selected cohorts, HLT can provide considerable post-transplant survival.

Outcome after heart-lung or lung transplantation in patients with Eisenmenger syndrome.

OBJECTIVE: The optimal timing for transplantation is unclear in patients with Eisenmenger syndrome (ES). We investigated post-transplantation survival and transplantation-specific morbidity after heart-lung transplantation (HLTx) or lung transplantation (LTx) in a cohort of Nordic patients with ES to aid decision-making for scheduling transplantation. METHODS: We performed a retrospective, descriptive, population-based study of patients with ES who underwent transplantation from 1985 to 2012. RESULTS: Among 714 patients with ES in the Nordic region, 63 (9%) underwent transplantation. The median age at transplantation was 31.9 (IQR 21.1-42.3) years. Within 30 days after transplantation, seven patients (11%) died. The median survival was 12.0 (95% CI 7.6 to 16.4) years and the overall 1-year, 5-year, 10-year and 15-year survival rates were 84.1%, 69.7%, 55.8% and 40.6%, respectively. For patients alive 1 year post-transplantation, the median conditional survival was 14.8 years (95% CI 8.0 to 21.8), with 5-year, 10-year and 15-year survival rates of 83.3%, 67.2% and 50.0%, respectively. There was no difference in median survival after HLTx (n=57) and LTx (n=6) (14.9 vs 10.6 years, p=0.718). Median cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis/kidney transplantation-free survival rates were 11.2 (95% CI 7.8 to 14.6), 6.9 (95% CI 2.6 to 11.1) and 11.2 (95% CI 8.8 to 13.7) years, respectively. The leading causes of death after the perioperative period were infection (36.7%), bronchiolitis obliterans syndrome (23.3%) and heart failure (13.3%). CONCLUSIONS: This study shows that satisfactory post-transplantation survival, comparable with contemporary HTx and LTx data, without severe comorbidities such as cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis, is achievable in patients with ES, with a conditional survival of nearly 15 years.

Evaluation of Risk Factors for Heart-Lung Transplant Recipient Outcome: An Analysis of the United Network for Organ Sharing Database.

BACKGROUND: Heart-lung transplantation (HLTx) is an effective treatment for patients with advanced cardiopulmonary failure. However, no large multicenter study has focused on the relationship between donor and recipient risk factors and post-HLTx outcomes. Thus, we investigated this issue using data from the United Network for Organ Sharing database. METHODS: All adult patients (age ≥18 years) registered in the United Network for Organ Sharing database who underwent HLTx between 1987 and 2017 were included (n=997). We stratified the cohort by patients who were alive without retransplant at 1 year (n=664) and patients who died or underwent retransplant within 1 year of HLTx (n=333). The primary outcome was the influence of donor and recipient characteristics on 1-year post-HLTx recipient death or retransplant. Kaplan-Meier curves were created to assess overall freedom from death or retransplant. To obtain a better effect estimation on hazard and survival time, the parametric Accelerated Failure Time model was chosen to perform time-to-event modeling analyses. RESULTS: Overall graft survival at 1-year post-HLTx was 66.6%. Of donors, 53% were male, and the mean age was 28.2 years. Univariable analysis showed advanced donor age, recipient male sex, recipient creatinine, recipient history of prior cardiac or lung surgery, recipient extracorporeal membrane oxygenation support, transplant year, and transplant center volume were associated with 1-year post-HLTx death or retransplant. On multivariable analysis, advanced donor age (hazard ratio [HR], 1.017; P=0.0007), recipient male sex (HR, 1.701; P=0.0002), recipient extracorporeal membrane oxygenation support (HR, 4.854; P<0.0001), transplant year (HR, 0.962; P<0.0001), and transplantation at low-volume (HR, 1.694) and medium-volume centers (HR, 1.455) in comparison with high-volume centers (P=0.0007) remained as significant predictors of death or retransplant. These predictors were incorporated into an equation capable of estimating the preliminary probability of graft survival at 1-year post-HLTx on the basis of preoperative factors alone. CONCLUSIONS: HLTx outcomes may be improved by considering the strong influence of donor age, recipient sex, recipient hemodynamic status, and transplant center volume. Marginal donors and recipients without significant factors contributing to poor post-HLTx outcomes may still be considered for transplantation, potentially with less impact on the risk of early postoperative death or retransplant.

Heart-lung transplantation over the past 10 years: an up-to-date concept.

OBJECTIVES: Heart-lung transplantation has been established as an effective treatment for patients with advanced cardiopulmonary failure. Over the years, the number of operations performed has declined. In 2015, only 38 adult heart-lung transplants were reported worldwide. Since then, we have performed 16 operations in high-acuity patients with excellent postoperative outcomes. Herein, we review our single-centre experience with heart-lung transplantation over the past 10 years. METHODS: We retrospectively reviewed 49 heart-lung transplant recipients between 2008 and 2018 to investigate the patient characteristics and outcomes while comparing those results across 2 cohorts (2008-2015, Era I, n = 30 and 2016-2018, Era II, n = 19). RESULTS: Our patient demographics and waitlist time did not significantly change over time. However, the lung allocation score was significantly higher in Era II compared to Era I (51.1 ± 19.8 in Era II and 41.6 ± 19.5 in Era I; P = 0.006). We also observed a higher rate-while not statistically significant-of preoperative and postoperative use of mechanical circulatory support in the present era. Although there is a trend of higher acuity in the present era, we continue to have excellent outcomes with 100% 30-day and 1-year survival. CONCLUSIONS: These results suggest that in a high-volume heart-lung transplant programme, excellent postoperative outcomes can be achieved even in patients with rapid and severe cardiopulmonary decline and that, to this day, heart-lung transplantation remains a viable option for patients with advanced cardiopulmonary disease.

Lung and heart-lung transplantation in pulmonary arterial hypertension.

BACKGROUND: Real use of lung (LT) and heart-lung (HLT) transplantation in pulmonary arterial hypertension (PAH) is unknown. The objectives were to describe the indication of these procedures on PAH treatment in a national cohort of PAH patients, and to analyze the potential improvement of its indication in severe patients. METHODS: Eligibility for LT/HLT was assessed for each deceased patient. Incident patients from REHAP diagnosed between January 2007 and March 2015 and considered eligible for LT/HLT were grouped as follows: those who finally underwent transplantation (LTP) and those who died (D-Non-LT). FINDINGS: Of 1391 patients included in REHAP, 36 (3%) were LTP and 375 (27%) died. Among those who died, 36 (3%) were D-Non-LT. LTP and D-Non-LT were equal in terms of age, gender, and clinical status. Ten percent of those who died were functional class I-II. Patients functional class IV were less likely to undergo LT (8.3% LTP vs. 30.6% D-Non-LT, p = 0.017). Patients with idiopathic and drug/toxin-associated PAH were more likely to undergo LT (44.4% LTP vs. 16.7% D-Non-LT, p = 0.011). CONCLUSIONS: The present results show that the use of LT/HLT could double for this indication. Relevant mortality in early functional class reflects the difficulties in establishing the risk of death in PAH.

Overview of Lung Transplantation, Heart-Lung Transplantation, Liver-Lung Transplantation, and Combined Hematopoietic Stem Cell Transplantation and Lung Transplantation.

Lung transplantation (LTx) has evolved to represent the therapy of choice for many patients with end-stage lung diseases. Appropriate candidate selection for LTx is an important determinant of a positive outcome from transplantation. Posttransplantation survival has steadily improved, but long-term survival continues to be a challenge with a median survival of 5.8 years. Similarly, combined heart-lung transplantation and simultaneous liver-lung transplantation has been performed successfully in select patients who are not expected to survive either organ transplant alone. Moreover, LTx has been performed in patients who develop end-stage pulmonary complications following hematopoietic stem cell transplantation.

Lung or Heart-Lung Transplant in Pulmonary Arterial Hypertension: What Is the Impact of Systemic Sclerosis?

OBJECTIVES: Little is known about recipient characteristics and outcomes of patients with pulmonary arterial hypertension undergoing lung transplant, particularly those with systemic sclerosis-associated disease. Here, we describe the characteristics and outcomes of patients with pulmonary arterial hypertension undergoing lung transplant, focusing on systemic sclerosis-associated disease. MATERIALS AND METHODS: This retrospective study included pulmonary arterial hypertension patients undergoing lung or heart-lung transplant between July 1992 and August 2013 at a single center. RESULTS: We evaluated 51 patients with pulmonary arterial hypertension (37.3% males; mean age of 45.3 ± 11.9 y). Of 51 patients, 9 (17.6%) had systemic sclerosis-associated pulmonary arterial hypertension. Pulmonary arterial hypertension patients without systemic sclerosis-associated disease had higher mean pulmonary arterial pressure (P = .002), higher pulmonary vascular resistance (P = .008), and were more likely to have severe right ventricular systolic dysfunction (P = .006) than individuals with the disease. Mean hospital stay posttransplant was similar in the 2 groups (42.2 ± 43.3 vs 43.1 ± 19.4 d; P = .20). Higher pretransplant creatinine clearance (P = .0005), forced vital capacity (P = .01), and absence of vasopressor/inotrope use (P = .03) were associated with shorter hospital stay. Mortality for pulmonary arterial hypertension patients with versus without systemic sclerosis-associated disease was 0% versus 13% at 1 year, 29% versus 24% at 2 years, and 86% versus 53% at 5 years. Female sex (hazard ratio, 0.23; 95% confidence interval, 0.08-0.68) and less severe tricuspid regurgitation (hazard ratio, 0.31; 95% confidence interval, 0.11-0.89) were independently associated with long-term survival. CONCLUSIONS: Pulmonary arterial hypertension patients with versus without systemic sclerosis-associated disease have comparable short-term and 2-year outcomes after lung or heart-lung transplant. Female sex and less severe tricuspid regurgitation were independently associated with better long-term survival. These outcomes did not vary when adjusted for the year of transplant.

Impact of Obesity on Heart and Lung Transplantation: Does Pre-Transplant Obesity Affect Outcomes?

Increasing prevalence of obesity has led to a rise in the number of prospective obese heart and lung transplant recipients. The optimal management strategy of obese patients with end-stage heart and lung failure remains controversial. This review article discusses and provides a summary of the literature surrounding the impact of obesity on outcomes in heart and lung transplantation. Studies on transplant obesity demonstrate controversy in terms of morbidity and mortality outcomes and obesity pre-transplantation. However, the impact of obesity on outcomes seems to be more consistently demonstrated in lung rather than heart transplantation. The ultimate goal in heart and lung transplantation in the obese patient is to identify those at highest risk of complication that may warrant therapies to mitigate risk by addressing comorbid conditions.

Renal transplantation outcomes following heart and heart-lung transplantation.

BACKGROUND: Chronic kidney disease is a frequent complication following heart and combined heart-lung transplantation. The aim of this study was to analyse the outcome of a subsequent renal transplant in heart, lung and heart-lung transplantation recipients. METHODS: All heart, lung and heart-lung transplant recipients who received a subsequent renal transplant over a 27-year period in a national heart and lung transplant centre were included in this study. RESULTS: A total of 18 patients who had previously undergone heart (n = 6), lung (n = 7) and heart-lung (n = 5) transplantation received a renal transplant. The mean duration to development of end-stage kidney disease (ESKD) was 115 ± 45.9 months. The most common contributor to ESKD was calcineurin inhibitor nephrotoxicity. The 5-year patient survival and graft survival rates were 91.7 and 85.6%, respectively. The median creatinine level at the most recent follow-up was 123 µmol/L, IQR 90.8-147.5. CONCLUSIONS: The overall outcome of renal transplantation following previous non-renal solid organ transplantation is excellent considering the medical complexity and co-morbidities of this patient population. Renal transplantation represents an important treatment option for ESKD in non-renal solid organ transplant recipients.

History of Lung and Heart-Lung Transplantation, With Special Emphasis on German-Speaking Countries.

The first experimental lung transplants were performed in 1947 by the Russian surgeon V.P. Demikhov. Thereafter, various aspects associated with lung transplantation were studied by groups from Italy, France, and mainly the United States. The first clinical lung transplant took place in Jackson, Mississippi, in 1963 and was performed by D. Hardy. Until 1983, a total of 45 lung transplants were carried out at various centers, but only one patient transplanted in Ghent by F. Derom in 1968 survived for 10 months, whereas all other patients survived only hours to a few days. In 1983 at Toronto General Hospital, a single-lung transplant was performed that survived almost 7 years. From the same institution, the first long-term survivor after double-lung transplantation was reported in 1986. The first lobar transplant from a live donor was performed by V.A. Starnes at Stanford in 1990. The first heart-lung transplantation was performed in Houston by D.A. Cooley in 1968. Even though the girl who received this transplant survived only for 14 hours, this case showed that this kind of procedure can work. The first long-term survival was achieved by B. Reitz in 1981 in Stanford. In the German-speaking countries, successful lung and lung-heart transplants were reported between 1984 and 1993 and are described in detail.

Induction immunosuppression for combined heart-lung transplantation.

BACKGROUND: Research on induction immunosuppression in patients undergoing combined heart-lung transplantation (HLTx) is limited. METHODS: The United Network for Organ Sharing database was queried from 2000 to 2013 to examine the influence of induction immunosuppression for combined HLTx in adult (≥18 years) and adolescent (≥12 and <18 years) recipients. RESULTS: Of 394 eligible combined HLTx cases (361 adults, 33 adolescents), 384 were included in univariate Cox analysis and 116 in the multivariate Cox model. Univariate analysis demonstrated no differences in survival by induction medication and no difference among the most common maintenance immunosuppression regimens. Adjusting for use of corticosteroids, multivariate analysis demonstrated no benefit of basiliximab (HR=3.582; 95% CI: 0.966, 13.279; P=.056), thymoglobulin/antilymphocyte globulin (ALG)/antithymocyte globulin (ATG) (HR=0.808; 95% CI: 0.134, 4.888; P=.817), alemtuzumab (HR=0.369; 95% CI: 0.087, 1.563; P=.176), or other induction medications (HR=1.511; 95% CI: 0.146, 15.610; P=.729), compared to no induction medication, with respect to mortality hazard post-HLTx. There were also no differences in treated acute rejection episodes by type of induction immunosuppression. CONCLUSIONS: Induction immunosuppression with contemporary agents does not improve survival after combined HLTx.

State of the Art of Combined Heart-Lung Transplantation for Advanced Cardiac and Pulmonary Dysfunction.

Over the last several decades, significant advances and improvements in care of transplant patients have resulted in markedly improved outcomes. A number of options are available for patients with advanced cardiopulmonary dysfunction requiring transplantation. There is a debate about when isolated heart or isolated lung transplantation is no longer possible or advisable and combined heart-lung transplantation is justified. Organ availability and allocation severely limit the latter option to very few well-selected patients. We review practice patterns, trends, and outcomes after triple-organ heart-lung transplant (HLTx) worldwide, as well as our own experience with heart-lung transplant in the modern era.

Retransplant and Medical Therapy for Cardiac Allograft Vasculopathy: International Society for Heart and Lung Transplantation Registry Analysis.

Cardiac retransplantation for heart transplant recipients with advanced cardiac allograft vasculopathy (CAV) remains controversial. The International Society for Heart and Lung Transplantation Registry was used to examine survival in adult heart recipients with CAV who were retransplanted (ReTx) or managed medically (MM). Recipients transplanted between 1995 and 2010 who developed CAV and were either retransplanted within 2 years of CAV diagnosis (ReTx) or alive at ≥2 years after CAV diagnosis, managed medically (MM), without retransplant, constituted the study groups. Donor, recipient, transplant characteristics and long-term survival were compared. The population included 65 patients in ReTx and 4530 in MM. During a median follow-up of 4 years, there were 24 deaths in ReTx, and 1466 in MM. Survival was comparable at 9 years (55% in ReTx and 51% in MM; p = 0.88). Subgroup comparison suggested survival benefit for retransplant versus MM in patients who developed systolic graft dysfunction. Adjusted predictors for 2-year mortality were diagnosis of CAV in the early era and longer time since CAV diagnosis following primary transplant. Retransplant was not an independent predictor in the model. Challenges associated with retransplantation as well as improved CAV treatment options support the current consensus recommendation limiting retransplant to highly selected patients with CAV.

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.