Incidence, risk factors, and outcomes of postoperative stroke in combined heart-lung transplantation: A retrospective cohort study of the UNOS registry.

Stroke is a well-characterized complication of isolated heart and lung transplantation, but has not been described in combined heart-lung transplantation (HLTx). We retrospectively reviewed national U.S. data to describe the incidence, risk factors, and impact of postoperative stroke in HLTx recipients. Of 871 heart-lung recipients between 1994-2022, 35 (4.0%) experienced stroke, and the incidence increased over time, trending toward significance (p-trend = .07). After adjustment, extracorporeal membrane oxygenation (ECMO) (Adjusted odds ratio [aOR] = 2.63, 95%CI = [1.13-6.11]) and pre-transplant implantable defibrillator (aOR = 2.86, 95%CI = [1.20-6.81]) were independent risk factors for stroke. Postoperative stroke is common and is increasing in an era where organ allocation is driven by mechanical circulatory support (MCS) bridging.

Case Report: Parvovirus B19 infection complicated by hemophagocytic lymphohistiocytosis in a heart-lung transplant patient.

Immunosuppressed patients can contract parvovirus B19, and some may experience hemophagocytic lymphohistiocytosis (HLH). Herein, we describe the first report of hemophagocytic lymphohistiocytosis in a heart-lung transplant patient with concomitant parvovirus B19 infection. The patient was treated with intravenous immune globulin (IVIG) and the features of HLH were remission. This instance emphasizes the significance of parvovirus B19 monitoring in transplant patients with anemia; if HLH complicates the situation, IVIG may be an adequate remedy. Finally, a summary of the development in diagnosing and managing parvovirus B19 infection complicated by HLH is provided.

Outcomes of heart-lung transplantation in Eisenmenger syndrome compared to primary pulmonary hypertension.

OBJECTIVE: Heart-Lung Transplantation (HLTX) is required both in primary pulmonary hypertension (PPH) and Eisenmenger syndrome (ES) when there is associated end-stage heart disease. Although PPH is associated with an otherwise structurally normal heart, ES is associated with congenital heart defects, which may increase the complexity of the operation. This study analyzes if the diagnosis (PPH vs. ES) is related to short-term outcomes after HLTX. METHODS: Patients ≥18 years of age with PPH and ES who underwent HLTX were identified in the United Network for Organ Sharing database from 2005 to 2021. Patients were propensity score matched on heart and lung listing status at the time of transplant. Univariable, multivariable, and Kaplan-Meir survival analyses were performed. RESULTS: The unmatched cohort had 128 PPH and 44 ES patients, and the matched cohort had 44 patients in each group. PPH patients had lower waitlist times and PA pressures but higher FEV1, heart, and lung listing status and ECMO bridge. There were no differences in immediate postoperative outcomes such as dialysis, stroke, and airway dehiscence. PPH patients had a higher treatment rejection in the first year. The 30-day, 1-year, and 3-year survival were better in the PPH group. However, a landmark analysis excluding deaths within 30 days eliminated differences in survival between the groups. Post-transplant dialysis and postoperative mechanical ventilation >5 days were risk factors for 1-year mortality in ES. CONCLUSION: The short-term outcomes of HLTX are inferior in ES compared to PPH and much of the attrition in ES occurs in the immediate postoperative period.

Evolutionary Description of Heart Transplantation and Heart-Lung Transplantation in Congenital Heart Disease.

BACKGROUND: Currently, a high percentage of patients with congenital heart disease (CHD) reach adulthood. The consequence is that more and more patients will require a heart transplant (HTx) or heart-lung transplant (HLTx). The objective of the study was to analyze the evolution and temporary trend of the number of HTxs and HLTxs in patients with and without CHD. METHODS: We performed a retrospective analysis of all HTxs and HTLxs from a Spanish transplant hospital. Retransplant and other combined transplants were excluded. HTx and HLTx were divided into 2 groups (CHD or non-CHD). The number of procedures of each modality was grouped in 5 years. RESULTS: A total of 930 HTxs were analyzed between 1987 and 2020; 36 were CHD (18 HTxs and 18 HLTxs). HTx and HLTx in CHD showed a growing progressive trend, probably because of the greater number of these patients who reach adulthood and finally develop advanced heart failure. HTx in patients without CHD showed a very high rise in the first decade, reaching the maximum peak around the year 2000, with a poststabilization trend or even progressive reduction in the number of procedures. HLTx in patients without CHD showed a marked ascent during the first decade with a peak around 2005 and subsequent significant decline in recent years practically in disuse, probably because of the possibility of circulatory assistance in the case of right ventricular failure. CONCLUSIONS: The number of HTxs and HLTxs in CHD has a progressive rise. The number of HTx in patients without CHD remains relatively stable. HLTx in patients without CHD shows a marked decrease.

Size matching in combined heart-lung transplant: An undersized predicted heart mass is associated with increased mortality.

BACKGROUND: Numerous studies have analyzed the consequences of donor-recipient organ size mismatch within both heart and lung transplantation. However, there is very little data on size matching in combined heart-lung transplantation (HLTx). We reviewed how donor/recipient predicted total lung capacity (pTLC), predicted heart mass (pHM), weight, and height ratios affect HLTx survival and graft rejection outcome. METHODS: We performed a retrospective analysis on adult HLTx patients using the UNOS database. Overall survival at 1- and 5-years, as well as 5-years bronchiolitis obliterans syndrome (BOS) and coronary artery vasculopathy (CAV) development, were the outcomes of interest. Each sizing modality was split into 5 groups for survival analysis and 3 groups for graft rejection analysis based on an approximately equal size-matched reference group. RESULTS: In total, 747 patients were analyzed in our study. Of the 4 sizing modalities, only pHM ratio had a significant difference in acute and long-term survival. In particular, a severely undersized pHMr of < 83% was associated with an increased risk of mortality compared to an approximately equally sized match (1-year: HR=1.95, 95% CI=1.30-2.91, p = 0.001; 5-year: HR = 1.47, 95% CI = 1.05-2.06, p = 0.027). No sizing metric was predictive of BOS or CAV development. CONCLUSION: Our analysis supports the use of pHM ratio for size matching in HLTx. Based on our results, a donor/recipient pHM ratio of >83% should be achieved to minimize mortality risk associated with sizing mismatch.

Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients.

AIMS: Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients. METHODS AND RESULTS: A total of 50 transplant patients [1-3 years post heart (42), lung (7), or heart-lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness. CONCLUSIONS: The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.

Risk assessment of chronic lung allograft dysfunction phenotypes: Validation and proposed refinement of the 2019 International Society for Heart and Lung Transplantation classification system.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a heterogeneous condition. Characterization of CLAD phenotypes is essential to enhance the understanding of pathogenesis and guide new therapies. The study objective was to validate the new International Society for Heart and Lung Transplantation (ISHLT) CLAD classification system and further explore patients who do not fall into the defined CLAD sub-categories. METHODS: We performed a single-center, retrospective cohort study of adult, first, bilateral lung transplants performed from 2010 to 2015. Patients with CLAD were classified on the basis of the 2019 ISHLT consensus document. CLAD phenotypes and other potential predictors of survival after CLAD onset were assessed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Among the 174 subjects with CLAD, 104 (59.8%) had bronchiolitis obliterans syndrome (BOS), 16 (9.2%) restrictive allograft syndrome (RAS), 9 (5.2%) mixed, and 19 (10.9%) undefined phenotype. A total of 26 patients (14.9%) did not match any of these 4 categories and remained unclassified. Allograft survival post-CLAD onset was longer for patients with BOS (median, 500 days) than patients with RAS (median, 372 days) or mixed (median, 328 days). The 45 patients (26.8%) with undefined/unclassified phenotype were combined and recategorized on the basis of the presence or absence of characteristic RAS-like opacities on chest imaging; those with RAS-like opacities had significantly worse allograft survival than patients with BOS (hazard ratio, 2.14; 95% confidence interval, 1.17-3.93; p = 0.014) and similar survival to RAS or mixed phenotype. CONCLUSIONS: The new ISHLT CLAD phenotype classification is informative with regards to post-CLAD outcomes. Chest imaging demonstrating persistent parenchymal or pleural fibrosis may be used for risk-stratification of patients who do not match the major CLAD phenotypes.

The effect of veno-arterial extracorporeal oxygenation and nasogastric tube administration on the pharmacokinetic profile of abacavir, lamivudine and dolutegravir: a case report.

BACKGROUND: Pharmacokinetic (PK) changes can affect antiretroviral (ARV) systemic exposure for critically ill patients living with HIV (CI-PLWH). Studies to guide ARV adjustments in this population are limited. METHODS: A PK analysis was conducted in a 44-year-old CI-PLWH who presented for a heart and lung transplant on veno-arterial extracorporeal membrane oxygenation (VA ECMO). Home ARV therapy (ART) of co-formulated abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) was continued. ARV serum concentrations were obtained during and after VA ECMO. Two blood levels were drawn at 1 h, for maximum serum concentration (Cmax) and a serum trough (Ct). ARVs were given as a single tablet crushed via nasogastric tube. RESULTS: Area under the concentration-time curve (AUC0-t) was calculated using non-compartmental analysis. Cmax and AUC0-t were higher during VA ECMO compared with post-decannulation. The Cmax of ABC was >2.5-fold higher than the mean in the reference. Cmax and Ct post VA ECMO were within range of referenced literature for all ARVs. Cmax and AUC0-t of DTG post VA ECMO was approximately four- to fivefold lower than referenced literature. HIV virological suppression was maintained throughout the hospitalization. CONCLUSIONS: ART adjustments would not be required for this patient. Additional studies are needed to assess effects of VA ECMO and crushed tube administration of ARVs in CI-PLWH.

Granuloma in the explanted lungs: Infectious causes and impact on post-lung transplant mycobacterial infection.

INTRODUCTION: The significance of granuloma in explanted lungs of lung transplant recipients (LTR) on the development of post-transplant mycobacterial infection is unclear. METHODS: A retrospective review comparing LTRs and heart-lung transplant (H-LTR) recipients with granuloma in the explanted lungs between 2000 and 2012 (excluding those LTRs with granuloma due to sarcoidosis) and LTRs or H-LTRs without granuloma. Patients were followed for 2 years post-transplant. RESULTS: A total of 144 LTRs and 4 H-LTRs with granulomas (75 necrotizing and 73 non-necrotizing) and a comparator cohort of 144 LTRs and 4 H-LTRs without granuloma were analyzed. In LTRs with granulomas, identification of infectious organisms was more common by histopathology (35 AFB and 22 fungal) compared to cultures (six NTM and seven fungal) taken around time of the transplant. LTRs with granulomas were more likely to have pre-transplant non-tuberculous mycobacteria (NTM) infection compared to LTRs without granuloma; P < .01. In the multivariate analysis, having granuloma or positive mycobacterial cultures at time of transplant were associated with increased risk of post-transplant mycobacterial infection (HR = 1.8 95% CI [1.024-3.154]; P = .041 and HR = 2.083 95% CI [1.011-4.292]; P = .047). Although there was a trend toward increase mycobacterial disease in those with granulomas P = .056, there was no difference in survival post-transplantation between those with or without granuloma in the explanted lung; P = .886. CONCLUSION: The presence of granuloma in the explanted lungs of LTRs or positive mycobacterial cultures at time of transplant is associated with an increased risk of mycobacterial infection post-transplant.

Romiplostim as a transfusion saving strategy in 20 patients after heart or lung transplantation: a single centre before-after pilot study.

BACKGROUND: Thrombocytopenia is a common disorder after heart or lung transplantation. Platelet transfusion is often required to maintain haemostasis but represents a specific cause of morbidity and mortality in this setting including alloimmunisation and graft rejection. STUDY DESIGN AND METHODS: As part of a health-care quality improvement project, in a single-centre before-after pilot study, the relevance of a platelet transfusion saving strategy based on romiplostim administration after transplantation was assessed in patients with platelet count <100 × 109/L. Transfusions on days 28 and 90 were compared using propensity matched score for adjustment of demographic characteristics at baseline. The primary outcome was platelet transfusion until day 28 after transplantation. RESULTS: Ninety-three patients were analysed (73 before vs. 20 after). The median [interquartile range] number of platelet concentrate was 1 [0;4.0] before versus 0.5 [0;2.0] in the after period, mean difference 0.5 confidence interval 95% [-0.7 to 1.7], p = 0.39. On day 28, median [interquartile range] red blood cell transfusion was significantly higher in the before versus the after period, 7 [2.0;13.5] versus 6 [1.5;8.5], mean difference 3.2 CI 95% [0.4-6.0], p = 0.02. At 6 months, the rate of patients with de novo anti-human leukocyte antigen alloimmunisation was 45% before versus 53% in the after period (p = 0.56). Deep venous thrombosis was detected in nine patients (12%) before versus seven patients (35%) in the after period (p = 0.04). CONCLUSION: Romiplostim did not significantly reduce platelet transfusion after heart or lung transplantation. Its relevance and safety in a global transfusion strategy remains to be studied in this setting in a large randomised study.

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.

Post-transplant diabetes mellitus associated with heart and lung transplant.

BACKGROUND: The incidence of post-transplant diabetes (PTDM) is variable primarily due to a lack of standardised diagnostic criteria. AIM: This study aimed to assess the incidence of PTDM in heart and lung transplant (HLT) patients and to review if the management of these patients is in accordance with the 2014 American Society of Transplantation guidelines. METHODS: This was a retrospective study in the Mater Misericordiae University Hospital, Dublin, Ireland. Data was collected from the patients who had undergone HLT. RESULTS: All patients who had a heart and/or lung transplant between 2005 and 2017 were identified. The majority of our patients had lung 111 (53.9%), heart 94 (45.6%) and combined heart/lung 1(0.5%) transplants. A total of 174 (84.5%) patients were screened for diabetes pre-transplantation. Two hundred five (99.9%) patients were screened for PTDM post-surgery. The cumulative incidence for PTDM was 19.4% (40/206). All patients with PTDM were on prednisolone, 32 (80%) on tacrolimus and 4 (10%) on cyclosporine. CONCLUSIONS: The cumulative incidence of post-transplant diabetes in our cohort was 19.4%. The majority of the patients were screened before and after transplant for glucose abnormality. The authors recommend that all patients should be managed in a multidisciplinary setting including transplant physicians, endocrinlogist, diabetes nurse specialists, transplant nurses and dietitians.

Impact of combined heart and lung transplantation on bronchiolitis obliterans syndrome, cardiac allograft vasculopathy, and long-term survival.

BACKGROUND: Evidence from animal studies and small case series suggests that primary graft dysfunction occurs less often following combined organ transplantation than following isolated organ transplantation. In this large-scale national registry study, we aimed to investigate whether survival and the rates of bronchiolitis obliterans syndrome (BOS) and coronary allograft vasculopathy (CAV) are affected by simultaneous heart and/or lung transplantation (HLTx). METHODS: Clinical data from the United Network of Organ Sharing database were retrospectively reviewed to identify transplant-naive patients who had undergone heart and/or lung transplantation between 1987 and 2016. The comparisons were conducted for isolated vs combined organ transplant. The outcomes included all-cause mortality, as well as the incidence of BOS and CAV RESULTS: Of the 98,310 patients reviewed, 63,976, 1,189, and 33,145 had received isolated heart transplantation (iHTx) (65%), HLTx (1%), and isolated lung transplantation (iLTx) (34%), respectively. In the early post-operative period, the mortality rates were higher after HLTx than after iHTx or iLTx (on crude and propensity score-matched analyses). However, the adjusted hazard risk for mortality associated with HLTx was significantly lower relative to the iLTx-associated risk beyond 3 years postoperatively, and similar relative to the iHTx-associated risk beyond 7 years postoperatively. On both crude and adjusted analyses, the incidence of BOS and CAV was significantly lower after HLTx than after iHTx or iLTx (p < 0.001 for all comparisons). CONCLUSIONS: Combined (rather than single) organ transplantation may provide immunoprotective benefits enhancing long-term survival and attenuating the risk of BOS and CAV.

[Selection of lung transplant candidates in France in 2019]. / Sélection des candidats à la transplantation pulmonaire en France en 2019.

INTRODUCTION: In 2015, the International Society for Heart and Lung Transplantation (ISHLT) published a consensus document for the selection of lung transplant candidates. In the absence of recent French recommendations, this guideline is useful in order to send lung transplant candidates to the transplantation centers and to list them for lung transplantation at the right time. BACKGROUND: The main indications for lung transplantation in adults are COPD and emphysema, idiopathic pulmonary fibrosis and interstitial diseases, cystic fibrosis and pulmonary arterial hypertension (PAH). The specific indications for each underlying disease as well as the general contraindications have been reviewed in 2015 by the ISHLT. For cystic fibrosis, the main factors are forced expiratory volume in one second, 6-MWD, PAH and clinical deterioration characterized by increased frequency of exacerbations; for emphysema progressive disease, the BODE score, hypercapnia and FEV1; for PAH progressive disease or the need of specific intravenous therapy and NYHA classification. Finally, the diagnosis of fibrosing interstitial lung disease is usually a sufficient indication for lung transplantation assessment. OUTLOOK AND CONCLUSION: These new recommendations, close to French practices, help clinicians to find the right time for referral of patients to transplantation centers. This is crucial for the prognosis of lung transplantation.

Heart or heart-lung transplantation for patients with congenital heart disease in England.

BACKGROUND: Increased longevity in patients with congenital heart disease (CHD) is associated with late complications, mainly heart failure, which may not be amenable to redo surgery and become refractory to medical therapy and so, trigger referral for transplantation. We assessed the current role and future prospects of heart and heart-lung transplantation for patients with CHD in England. METHODS: We performed a retrospective analysis of hospital episodes for England for 1997-2015, identifying patients with a CHD code (ICD-10 'Q2xx.x'), who underwent heart or heart-lung transplantation. RESULTS: In total, 469 transplants (82.2% heart and 17.8% heart-lung) were performed in 444 patients. Half of patients transplanted had mild or moderate CHD complexity, this percentage increased with time (p=0.001). While overall, more transplantations were performed over the years, the proportion of heart-lung transplants declined (p<0.0001), whereas the proportion of transplants performed in adults remained static. Mortality was high during the first year, especially after heart-lung transplantation, but remained relatively low thereafter. Older age and heart-lung transplantation were strong predictors of death. While an increase in CHD transplants is anticipated, actual numbers in England seem to lag behind the increase in CHD patients with advanced heart failure. CONCLUSIONS: The current and future predicted increase in the numbers of CHD transplants does not appear to parallel the expansion of the CHD population, especially in adults. Further investment and changes in policy should be made to enhance the number of donors and increase CHD transplant capacity to address the increasing numbers of potential CHD recipients and optimise transplantation outcomes in this growing population.

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.