Trends and Outcomes of Combined Heart-Kidney and Heart-Lung Transplantation Over the Past Two Decades.

INTRODUCTION: Combined heart-kidney transplantation (HKTx) and combined heart-lung transplantation (HLTx) remain the definitive therapy for patients with end-stage heart failure with concomitant end-stage renal or lung failure. We sought to study trends and outcomes of HKTx and HLTx over the last two decades. METHODS: The United Network for Organ Sharing registry was used to identify all adult patients (aged >18 y) who underwent HKTx and HLTx between 2001 and 2021. Patients were divided into 5-y groups by the year of transplantation (2001-2006, 2007-2011, 2012-2016, and 2017-2021). Primary outcome was 1-y posttransplantation mortality. Kaplan-Meier and multivariable Cox proportional hazards models were used for unadjusted and risk-adjusted survival analyses, respectively. RESULTS: A total of 2301 HKTx and 567 HLTx patients were included. Between 2001 and 2021, HKTx volume increased from 25 to 344 patients (P < 0.001) and centers performing HKTx increased from 19 to 76 (P < 0.001). On unadjusted analysis, 1-y survival after HKTx improved from 86.7% in 2001-2006 to 89.0% in 2017-2021 (log-rank, P = 0.005). On risk-adjusted analysis, the hazard ratio of 1-y mortality for 2017-2021 was 0.62 (0.39-1.00, P = 0.048) compared with that for 2001-2006. Between 2001 and 2021, HLTx volume increased from 21 to 43 patients (P < 0.001) and centers performing HLTx increased from 12 to 20 (P = 0.047). On unadjusted analysis, 1-y survival after HLTx improved from 68.9% in 2001-2006 to 83.9% in 2017-2021 (log-rank, P = 0.600). On risk-adjusted analysis, the hazard ratio of 1-y mortality for 2017-2021 was 0.37 (0.21-0.67, P = 0.001) compared with that for 2001-2006. CONCLUSIONS: Over the last two decades, HKTx volume substantially increased and HLTx experienced resurgent growth. One-year survival persistently improved for both procedures, especially over the past 5 y.

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.

Influence of cardiac diagnosis on outcomes of pediatric heart-lung transplantation.

OBJECTIVE: Pediatric Heart-lung transplant (HLTX) is performed for endstage congenital heart disease (CHD) with irreversible pulmonary hypertension or non-congenital heart disease (NCHD) with end-stage heart and lung disease. CHD could influence the outcomes of HTLX due to increased complexity of the operation as compared to NCHD. In this study we evaluated the influence of cardiac diagnosis on outcomes of pediatric HTLX. METHODS: The UNOS database (1987-2022) was queried for primary HTLX in patients <18 years. The data were extracted for demographics, pretransplant characteristics, post-transplant outcomes, and analyzed for the impact of cardiac diagnosis on post-transplant outcomes. Standard statistical tests were used. Survival was compared using the Kaplan-Meier method. RESULTS: Ninety of the 213 patients who underwent HLTX had CHD. There were no demographic differences. Heart listing status was similar but with a higher LAS score for NCHD. NCHD had higher pre-operative life support use (mechanical ventilation, inotropes or dialysis) but the use of ECMO as a bridge to transplantation was similar. Wait-list times were longer for CHD. The ischemic times were similar. Post-transplant dialysis, stroke, prolonged mechanical ventilation, and rejection were similar. Survival at 30-days, 1-year, and long-term survival at 17 years was similar. Non-survivors at 30-days post-transplant were on life support, used ECMO as a bridge, had lower wait-list times, longer ischemic times and had strokes. Non-survivors at 1-year had similar factors in addition to a higher dialysis use. CONCLUSION: Cardiac diagnosis had no impact on outcomes after Pediatric HLTX. Patients on life support or ECMO before transplantation were transplanted faster but with lower survival.

Procurement Trends, Indications, and Outcomes of Heart-Lung Transplantation in the Contemporary Era.

BACKGROUND: Evolving trends in organ procurement and technological innovation prompted an investigation into recent trends, indications, and outcomes following combined heart-lung transplantation (HLTx). METHODS: The United Network for Organ Sharing database was queried for all adult (≥18 years) HLTx performed between July 1, 2013 and June 30, 2023. Patients with previous transplants were excluded. The primary endpoint was the effect of donor, recipient, and transplantation characteristics on 1- and 5-year survival. Secondary analyses included a comparison of HLTx at high- and low-volume centers, an assessment of HLTx following donation after circulatory death (DCD), and an evaluation of HLTx volume over time. Cox proportional-hazards models were used to assess factors associated with mortality. Temporal trends were evaluated with linear regression. RESULTS: After exclusions, 319 patients were analyzed, of whom 5 (1.6%) were DCD. HLTx volume increased from 2013 to 2023 (p < 0.001). One- and 5-year survival following HLTx was 84.0% and 59.5%, respectively. One-year survival was higher for patients undergoing HLTx at a high-volume center (88.3% vs. 77.9%; p = 0.012). After risk adjustment, extracorporeal membrane oxygenation support 72 h posttransplant and predischarge dialysis were associated with increased 1-year mortality (HR = 3.19, 95% CI = 1.86-5.49 and HR = 3.47, 95% CI = 2.17-5.54, respectively) and 5-year mortality (HR = 2.901, 95% CI = 1.679-5.011 and HR = 3.327, 95% CI = 2.085-5.311, respectively), but HLTx at a high-volume center was not associated with either. CONCLUSIONS: HLTx volume has resurged, with DCD HLTx emerging as a viable procurement strategy. Factors associated with 1- and 5-year survival may be used to guide postoperative management following HLTx.

Contemporary Immunosuppression Management and 1-Year Outcomes in Dual Organ Heart Transplantation.

BACKGROUND: There have been limited reports on immunosuppression strategies and outcomes in dual organ heart transplant populations, primarily from before the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change. Recent data suggested that outcomes with heart-lung and heart-liver transplants remained comparable in the new allocation era, yet heart-kidney recipients have worse 1-year survival. METHODS: This single-center retrospective study evaluated adult heart-kidney, heart-liver, and heart-lung transplant recipients from September 2019 to May 2023. Immunosuppression regimen, infectious complications, and graft outcomes were collected for 12 months. RESULTS: A total of 36 patients (kidney n = 20, liver n = 9, and lung n = 7) were included in this study. Basiliximab was the most commonly employed induction strategy across the organ groups (12/20 in kidney, 4/9 in liver, and 7/7 in lung). All patients were on triple immunosuppression at 12 months posttransplant with prednisone wean achieved in one heart-liver recipient. Infection complications were frequently reported (95% kidney, 75% liver, 100% lung group). One patient went back to dialysis due to focal segmental glomerulosclerosis. One chronic lung allograft dysfunction was reported, but no other severe biopsy-proven rejection or retransplant was reported. The 1-year survival was 85% (17/20) in heart-kidney, 78% (7/9) in heart-liver, and 86% (6/7) in heart-lung recipients. CONCLUSION: This study summarized real-world immunosuppression strategies and outcomes in dual organ heart transplant recipients.

Pediatric heart transplantation: Looking forward after five decades of learning.

Heart transplantation has become the standard of care for pediatric patients with end-stage heart disease throughout the world. Since the first transplant was performed in 1967, the number of transplants has grown dramatically with 13 449 pediatric heart transplants being reported to The International Society of Heart and Lung Transplant (ISHLT) between January 1992 and June 30, 2018. Outcomes have consistently improved over the last few decades, specifically short-term outcomes. Most recent survival data demonstrate that recipients who survive to 1-year post-transplant have excellent long-term survival with more than 60% of those who were transplanted as infants being alive 25 years later. Nonetheless, the rates of graft loss beyond the first year have remained relatively constant over time; driven primarily by our poor understanding and lack of treatments for chronic allograft vasculopathy (CAV). Acute rejection, CAV, graft failure, and infection continue to be the major causes of death within the first 5 years post-transplant. In addition, renal dysfunction, malignancy, and the need for re-transplantation remain as significant issues that require close follow-up. Looking forward, key challenges include improving donor utilization rates (including donation after cardiac death (DCD) and the use of ex vivo perfusion devices), the development of non-invasive biomarkers for rejection, efforts to mitigate the long-term effects of immunosuppression, and prevention of CAV. It is not possible to cover the entire evolution of pediatric heart transplantation over the last five decades, but in this review, we hope to touch on key observations, lessons learned, and practice changes that have advanced the field, as well as glance ahead to the next decade.

Right lower lung midline herniation as a rare complication in an infant with heart-lung transplantation: A case report.

BACKGROUND: Lung herniation is a rare complication of heart-lung transplantation that can be fatal owing to vascular compromise and airway obstruction. To date, only five cases of lung herniation related to heart-lung transplantation have been reported in the literature; however, to the best of our knowledge, this is the first worldwide report of heart-lung transplantation-related lung herniation in an infant. METHODS: We describe the case of lung herniation as a rare heart-lung transplantation-related complication in an infant. A 12-month-old female baby developed severe bronchopulmonary dysplasia with severe pulmonary hypertension, and she underwent extracorporeal membrane oxygenation for cardiac collapse and lung support. Then, we performed heart-lung transplantation to manage the irreversible deterioration of her lung function. After the heart-lung transplantation, we found the radiological abnormalities persisted on follow-up chest radiographs until the 13th postoperative day diagnosed as lung herniation of the right lower lobe on chest computed tomography. RESULTS: After the relocation of the herniated lung, the clinical condition of the patient improved, and the patient is currently growing without any respiratory symptoms. CONCLUSIONS: In this case report, we emphasize that clinical awareness and high suspicion of this rare complication are needed for early diagnosis and proper treatment to prevent post-transplantation morbidity and mortality related to potential ischemic injury.

Circovirus Hepatitis Infection in Heart-Lung Transplant Patient, France.

In March 2022, a 61-year-old woman in France who had received a heart-lung transplant sought treatment with chronic hepatitis mainly characterized by increased liver enzymes. After ruling out common etiologies, we used metagenomic next-generation sequencing to analyze a liver biopsy sample and identified an unknown species of circovirus, tentatively named human circovirus 1 (HCirV-1). We found no other viral or bacterial sequences. HCirV-1 shared 70% amino acid identity with the closest known viral sequences. The viral genome was undetectable in blood samples from 2017-2019, then became detectable at low levels in September 2020 and peaked at very high titers (1010 genome copies/mL) in January 2022. In March 2022, we found >108 genome copies/g or mL in the liver and blood, concomitant with hepatic cytolysis. We detected HCirV-1 transcripts in 2% of hepatocytes, demonstrating viral replication and supporting the role of HCirV-1 in liver damage.

State of the art - Extracorporeal membrane oxygenation as a bridge to thoracic transplantation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has revolutionized the treatment of refractory cardiac and respiratory failure, and its use continues to increase, particularly in adults. However, ECMO-related morbidity and mortality remain high. MAIN TEXT: In this review, we investigate and expand upon the current state of the art in thoracic transplant and extracorporeal life support (ELS). In particular, we examine recent increase in incidence of heart transplant in patients supported by ECMO; the potential changes in patient care and selection for transplant in the years prior to updated United Network for Organ Sharing (UNOS) organ allocation guidelines versus those in the years following, particularly where these guidelines pertain to ECMO; and the newly revived practice of heart-lung block transplants (HLT) and the prevalence and utility of ECMO support in patients listed for HLT. CONCLUSIONS: Our findings highlight encouraging outcomes in patients bridged to transplant with ECMO, considerable changes in treatment surrounding the updated UNOS guidelines, and complex, diverse outcomes among different centers in their care for increasingly ill patients listed for thoracic transplant.

Revised Heart Allocation Policy Improved Waitlist Mortality and Waiting Time With Maintained Outcomes in En-Bloc Heart-Lung Transplant Candidates and Recipients.

The revised United Network for Organ Sharing heart allocation policy was implemented in October 2018. Using a national transplant database, this study evaluated the transplant rate, waitlist mortality, waiting time, and other outcomes of en-bloc heart-lung transplantation recipients. Adult patients registered on the national database for heart-lung transplants before and after the policy update were selected as cohorts. Baseline characteristics, transplant rates, waitlist mortality, waiting times, and other outcomes were compared between the two periods. In total, 370 patients were registered for heart-lung transplants during the pre- and post-periods. There were significantly higher transplant rates, shorter waitlist times, and substantially reduced waitlist mortality in the post-period. Registered patients waitlisted in the post-period had significantly higher utilization of intra-aortic balloon pumps, extracorporeal membrane oxygenation, and overall life support, including ventricular assist devices. Transplant recipients had significantly longer ischemic times, increased transport distances, and shorter waiting times before transplantation in the post-policy period. Transplant recipients held similar short-term survival before and after the policy change (log-rank test, p = 0.4357). Therefore, the revised policy significantly improved access to en-bloc heart-lung allografts compared with the prior policy, with better waitlist outcomes and similar post-transplant outcomes.

Double-lung versus heart-lung transplantation for end-stage cardiopulmonary disease: a systematic review and meta-analysis.

We compared posttransplant outcomes following double-lung transplantation (DLTx) and heart-lung transplantation (HLTx), based on a search of PubMed, Cochrane Library, and Embase, from inception to March 8, 2022, for studies that report outcomes of these procedures. We then performed a meta-analysis of baseline characteristics and posttransplant outcomes. Subgroup analyses were implemented according to indication, publication year, and center. This study was registered on PROSPERO (number CRD42020223493). Ten studies were included in this meta-analysis, involving 1230 DLTx patients and 1022 HLTx patients. The DLTx group was characterized by older donors (P = 0.04) and a longer allograft ischemia time (P < 0.001) than the HLTx group. The two groups had comparable 1-year, 3-year, 5-year, 10-year survival rates (all P > 0.05), with similar results identified in subgroup analyses. We found no significant differences in 1-year, 5-year, and 10-year chronic lung allograft dysfunction (CLAD)-free survival, length of intensive care unit stay and hospital stay, length of postoperative ventilation, in-hospital mortality, or surgical complications between the groups (all P > 0.05). Thus, DLTx provides similar posttransplant survival to HLTx for end-stage cardiopulmonary disease. These two procedures have a comparable risk of CLAD and other posttransplant outcomes.

The changing landscape of pediatric lung transplantation.

There has been a shift over decades in the diagnostic indications for lung transplantation in children; in particular, there has been a reduction in the proportion of pediatric cystic fibrosis (CF) patients undergoing lung transplantation early in life, and more transplants occurring in other diagnostic groups. Here, we examine trends in pediatric lung transplantation with regards to indications by analyzing data from the United Network of Organ Sharing, the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, and other sources. Over the past two years, there has been a precipitous decline in both the number of transplants due to CF and the proportion of CF cases relative to the total number of transplants, likely not solely due to the COVID-19 pandemic. In 2020, primary pulmonary arterial hypertension for the first-time surpassed CF as main indication for pediatric lung transplantation in the United States, a finding that is also reflected in international data. We discuss the effect of novel CFTR modulator therapies as a major factor leading to this shifting landscape. Based on our trending, pulmonary hypertension-related diagnoses and pediatric interstitial lung diseases are rising indications, for which we suggest adjustments of consensus guidelines around candidate selection criteria.

Should there be an age limit for advanced therapies?

Combined heart lung transplant has become a rare procedure. However, there is a significant number of patients potentially benefitting from replacement of both heart and lungs. This represents a quite diverse patient population. Decisions in patient selection have to be adjusted to individual needs and distinct constellation of the patient. Age may be a risk factor, but should be carefully integrated into the evaluation of perioperative and long term risks.

Risk of recipient age on 1-year mortality after simultaneous heart-lung transplantation.

BACKGROUND: Heart-lung transplantation (HLTx) is relatively uncommon, and there is a paucity of literature to suggest an age at which older recipients may be exposed to excess risk for mortality. This analysis aimed to identify a threshold of age that predicts adverse outcomes after HLTx. METHODS: The United Network of Organ Sharing registry was used to identify adult patients undergoing HLTx from 2005 to 2021. The primary outcome was 1-year mortality. Threshold regression was used to identify the threshold at which age impacts 1-year mortality. Kaplan-Meier analysis was used to model survival, and Cox proportional hazards modeling was used for risk-adjustment. RESULTS: We identified 453 patients undergoing HLTx. Threshold analysis identified that the risk for 1-year mortality was significantly elevated beyond an age of 58 years, and 47 (10.38%) patients were older than this threshold. On Kaplan-Meier analysis, 1-year survival was significantly lower in patients > 58 years compared to younger recipients (64.7% vs. 82.0%, p = .007). After risk adjustment, the hazard ratio for 1-year mortality in recipients older than 58 years was 2.27 (95% confidence interval [1.21-4.28], p = .011). CONCLUSION: A threshold for recipient age of 58 years of age may avoid excess 1-year mortality after HLTx. However, patients older than this threshold demonstrate acceptable early and midterm survival, and the majority survive to 1 year. Advanced age should be considered in patient selection for HLTx, but may not be a contraindication for candidacy particularly in the absence of other risk factors.

Surgical management of giant pulmonary artery aneurysms in patients with severe pulmonary arterial hypertension.

BACKGROUND AND AIM: Giant aneurysm of the pulmonary artery (PAA) is an extremely rare condition that may develop in patients with pulmonary arterial hypertension (PAH) which may be complicated by rupture, dissection or intravascular thrombus formation. The aim of this study was to examine available literature with regard to surgical strategies in patients undergoing transplantation for PAH with PAA. RESULTS: These patients were traditionally considered for heart-lung transplantation but more recently, there have been reports of successful lung transplantation with reconstruction of the pulmonary artery. CONCLUSIONS: Unless there is a mandatory indication for heart-lung transplantation, patients with PAH and PAA can undergo lung transplantation and reconstruction of the pulmonary artery without compromising the outcome.

ProtekDuo as a bridge to lung transplant and heart-lung transplant.

Recent advances in technology have led to significantly greater use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation with better outcomes. The novel ProtekDuo veno-venous ECMO (CardiacAssist, Inc.) has gained significance as it facilitates effective decompression of the right heart in patients with acute decompensation, while also providing consistent and effective gas exchange by eliminating recirculation. Here, we report two cases of effectively using ProtekDuo veno-venous ECMO: one case as a bridge to lung transplantation and another case as a bridge to heart-lung transplantation.

Impact of SARS-CoV-2 outbreak on heart and lung transplant: A patient-perspective survey.

BACKGROUND: The risk of COVID-19 is expected to be higher among solid organ transplant. The aim of the present study was to evaluate the incidence of COVID-19 and the impact of the SARS-CoV-2 outbreak on the personal hygiene and expectations in heart and lung transplant recipients. METHODS: A telephone survey of heart (n = 69) and lung (n = 41) transplant patients and a group of controls (n = 41) was conducted concerning personal hygiene before and after the outbreak; the impact on subjective expectations regarding graft outcome; symptoms possibly associated with SARS-CoV-2 infection; and diagnosis of COVID-19. RESULTS: Seventy nine percent of the patients declared they increased the use of face masks and handwash. Behavior at home regarding self-isolation did not change. About half the patients said they were afraid of the virus. A higher percentage of Lung transplant (LTX) were convinced that SARS-CoV-2 could have a negative impact on the outcome of their graft. 28% declared that they were afraid to come to the hospital for routine examinations and asked to postpone. Nine LTX and five Heart transplant (HTX) patients experienced symptoms that could have been associated with SARS-CoV-2 infection, but none of them underwent a nasopharyngeal swab. Only one LTX was diagnosed with the infection. CONCLUSIONS: In our study, we observed a low incidence of COVID-19 in heart and lung transplant patients (0.9%), similar to that of the general population of our Region. Isolation measures were already observed before the pandemic and were further strengthened in most cases. Particular attention should also be paid to new psychological and physical complications indirectly linked to the COVID-19 pandemic.

Long-term veno-arterial extracorporeal membrane oxygenation as a bridge to heart-lung transplant.

En bloc heart-lung transplantation still represents definitive therapy for end-stage cardiopulmonary failure. However, patients may critically decompensate while awaiting suitable donor organs and necessitate veno-arterial extracorporeal membrane oxygenation. In this article, we describe the combined use of central cannulation with the Berlin Heart EXCOR ventricular assist device cannulae and the CentriMag centrifugal pump as an extended bridge to heart-lung transplantation in three pediatric patients.

Changes in multiorgan heart transplants following the 2018 allocation policy change.

BACKGROUND: This study evaluated the impact of the heart allocation policy change in 2018 on the characteristics and outcomes of multiorgan transplants involving heart allografts. METHODS: Adults undergoing multiorgan heart transplantation from 2010 to 2020 were identified from the United Network for Organ Sharing (UNOS) registry. Transplants were stratified into occurring before versus after the October 2018 heart allocation change. The primary outcome was 1-year survival following transplantation. A Cox proportional hazards model was used to evaluate the risk-adjusted effect of the allocation policy change on outcomes between cohorts. RESULTS: A total of 1832 patients underwent multiorgan heart transplantation during the study period with 245 (13.37%) undergoing heart-lung transplantation, 244 (13.32%) undergoing heart-liver transplantation, and 1343 (73.31%) undergoing heart-kidney transplantation. There was a higher utilization of temporary MCSDs as well as longer ischemic times for all three types of transplantation following the policy change. Heart-lung and heart-liver recipients had a similar 1-year survival before and after the policy change (each p > .05). Renal failure requiring dialysis (29.5% vs. 39.4%, p = .001) as well as 1-year survival (88% vs. 82%; log-rank p = .01) were worse in the heart-kidney cohort after the organ allocation system modification. CONCLUSIONS: This study demonstrates similar trends in multiorgan transplants as has been observed in isolated heart transplants following the allocation change, including more frequent utilization of temporary mechanical support and longer ischemic times. Although outcomes have remained comparable in the new allocation era with heart-lung and heart-liver transplants, heart-kidney recipients have a worse 1-year survival following the change.

Is it time for a paradigm shift: Should double-lung transplant be considered the treatment of choice for idiopathic pulmonary arterial hypertension and giant pulmonary aneurysm?

Idiopathic pulmonary arterial hypertension is a rare condition, frequently complicated by pulmonary arteries' aneurysm. Aggressive medical therapy is often unsatisfactory and lung transplantation remains the only option. We report a unique case of severe idiopathic pulmonary arterial hypertension complicated by a giant pulmonary aneurism, massive pulmonary valve regurgitation, and right ventricle dysfunction. The patient was, as our first choice, listed for heart-lung transplantation and remained in emergency list for more than 7 months. Unfortunately, due to further clinical deterioration and the unavailability of a heart-lung bloc, plan B was mandatory. The patient underwent a combined procedure including: double lung transplant, pulmonary artery plasty, and sutureless pulmonary valve prosthesis with open deployment (first-in-man use in such scenario). Postoperative outcome was uneventful. Our thought is that double lung transplantation and conventional combined pulmonary artery/valve surgery should be considered as the first option avoiding excessive waiting times and potential further clinical deterioration.