Heart transplantation

The current scale of worldwide heart transplantation is well illustrated by the recent analysis of the International Society of Heart and Lung Transplantation (ISHLT) reporting on close to 5000 heart transplants from more than 250 centers worldwide . There is a broad spectrum of indications such as congenital heart disease and ischemic, hypertrophic, and restrictive cardiomyopathy . There is a continuous increase in transplant volume in North America but also in the world beyond Europe. Heart transplantation offers a 10-fold survival improvement with a near-normal quality of life. Thus, it remains the standard option for patients on the transplant waiting list and the gold standard for ultimate heart failure therapies.

Mechanical circulatory support has been a major breakthrough for operative management of patients suffering from end-stage heart failure. Specifically, the concepts of bridge to decision, transplantation, and destination therapy by ventricular assist devices offer new opportunities, challenges, and complimentary frameworks for these patients. As a result of technical progress and intense clinical evaluation, the algorithm of bridge to transplant therapy currently covers more than 50% of patients with end-stage heart disease.

The creation of the International Registry for mechanically assisted circulatory support (IMACS) was approved by the ISHLT in April 2011 . Major goals of this registry include the worldwide collection of data related to implantation and outcome of patients receiving cardiac assist devices. It serves to identify risk factors for complications and improve patient selection with the overall major objective to identify best practice toward improved outcomes. IMACS includes the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from the United States, the EUROMACS from Europe, the UK Registry, and the Japanese Mechanically Assisted Circulatory Support (JMACS) Registry. The IMACS registry included 5942 patients for the period 2013–2014 . One-year survival for patients with continuous flow technology is currently approximately 80%. Progress of the Ventricular Assist Device (VAD) technology led to improved survival and apparently low morbidity .

Lung transplantation

According to the latest adult lung and heart-lung transplantation report from the ISHLT, both the volume of lung transplants and the outcomes are improving. For instance, 134 transplant centers performed a total of 3973 lung transplantation procedures in 2014 . The most common indications are chronic obstructive pulmonary disease (COPD), a broad category of interstitial lung disease (ILD), and pulmonary fibrosis followed by bronchiectasis and idiopathic pulmonary hypertension . Lung transplantations performed between 1990 and 2014 had a median survival rate of 5.8 years. The unadjusted survival rates were 80% at 1 year, 65% at 3 years, and 54% at 5 years, but survival increased in the recent era of lung transplantation. Major causes of death consisted of graft failure and non-CMV infections . There are several center- and procedure-specific and recipient- or donor-related risk factors for mortality. These include lower transplant center volume, lower donor to recipient body mass index (BMI) ratio, older recipient, higher pre-transplant bilirubin, and donor age at the time of transplant .

Similar to heart transplantation, the concept of pre-transplantation mechanical support in the form of ECMO therapy as bridge to lung transplantation increased over the last 10 years . Because of novel technological developments such as the single-stage, bi-caval dual-lumen ECMO cannulas, patients on awake-ECMO can avoid mechanical ventilation and breathe spontaneously, remain mobile, and participate in physical therapy and prehabilitation, preserving and even improving their muscle tone, functional state, and conditioning. This major advance is associated with a favorable outcome compared to invasive mechanical ventilation. However, compared with patients without pre-transplant support, bridged patients still suffer from a higher incidence of primary graft dysfunction and lower survival rates .

Influence of institutional volume on postoperative complications and mortality

The relationship between institutional volume and outcome in general cardiothoracic surgery is well-established , and the increased mortality in low-volume institutions has been attributed to higher rates of postoperative complications . This has also been observed in the setting of heart transplantation. Grimm et al. demonstrated that low-volume institutions (<14 heart transplants per year) experienced greater incidence of complications, which were associated with a significantly reduced 90-day, 1-year, and 5-year survival . Potential reasons include superior surgical technique and greater resource availability in high-volume institutions.

A similar relationship has been demonstrated in lung transplantation as outcomes from high-volume centers are generally better, length of stay is shorter, and hospital costs are decreased compared to low-volume centers . The latest ISHLT report covering center activities between 2009 and 2015 indicates that nearly 30% of centers conducted less than 10 transplant procedures per year, while only 30% of centers had an average activity higher than 30 transplants per year. Only a minority of centers (10%) had an average volume of higher than 50 transplants per year . While such recognized center volume effect could prompt implementation of regionalization programs with the potential of saving lives, these need to be balanced by increased referral distances and their consequences in limiting access to care for rural populations .

Donor shortages

The greatest obstacle to cardiothoracic transplantation (similar to other solid organ transplantation) remains the discrepancy between the increasing number of eligible patients listed for transplantation and the availability of functionally suitable donor organs . Consequently, there are major initiatives to increase the number of potential organ donors, to adjust waiting lists, and to optimize organ allocation. Our regular thinking is that the available donor organ supply is far less than the demand, but we may simply not be utilizing enough of the available organs . Indeed, a closer analysis indicates that one of the crucial problems remains rejection of a large fraction of potential organ offers due to manifest or perceived organ dysfunction before and after donor death.

Interestingly, the rate of acceptance is widely different among transplant centers, countries, and continents, indicating uncertainties regarding this crucial part of the transplant process. For instance, the gap between demand and availability of cardiac allografts is larger in Europe than in the US. Surprisingly, the overall rate of heart transplants is about 30% less in the UK than the European average, mainly because of a remarkably low acceptance rate. Indeed, the rate of hearts procured and transplanted over the total of donors available is the lowest among the major transplant countries. For instance, 784 hearts were considered eligible for cardiothoracic donation in 2016, but only 189 hearts were transplanted . Similarly, only 20% of lungs are accepted from actual cadaveric donors. As these organs were mostly rejected because of poor function, it appears more could be done to preserve or at least attenuate the development of cardiac and pulmonary dysfunction in the donors after brain death.

There are additional issues related to the fact that the assessment by the retrieval team and the classifying of a potential donor organ as unacceptable is less than absolute. For instance, Ware and colleagues evaluated clinically rejected donor lungs and assessed them by physiological, microbiological, and histological methods . More than 80% of these lungs had no or only mild pulmonary edema, more than 70% demonstrated intact alveolar fluid clearance, and more than 60% were normal or only mildly abnormal on histological examination. They concluded that more than 40% of the rejected lungs would have been potentially suitable for transplantation. These are major revelations with huge implications to the volume and quality of rejected donor lungs, emphasizing an urgent need for significant improvement for the clinical and scientific assessment of donor lungs . We also believe that the specialties of anesthesia and critical care could do more in helping the exact evaluation of the cardiopulmonary status of the potential donor, especially in light of the relatively junior composition of the retrieval teams.

The Lung Allocation Score

Hospitals located within each OPO DSA are required to notify their federally designated OPO of all deaths and all imminent brain deaths as stipulated by the Hospital Conditions of Participation, issued in 1998. Transplant centers must notify patients in writing when they have been placed on the national transplant waiting list within 10 days of their registration. The national computer network, known as UNet, links all donors and listed candidates waiting for organs. In the US, patients are allowed to register at more than one transplant center; however, they must undergo separate evaluations for each center they decide to register with. Registering with multiple transplant centers does not guarantee a shorter time on the wait list.

Prior to the Lung Allocation Score (LAS), time on the waiting list prioritized lung allocation regardless of severity of disease. The LAS system came into use in 2005 and de-emphasized wait list time and focused more on transplant urgency to reduce wait list mortality and avoid futile transplants. It is the only recipient scoring system in the US for all solid organs, which incorporates post-lung transplant survival, as a variable in allocating lungs. The LAS score is derived from multiple clinical variables predictive of survival during the following year on the waiting list without a transplant versus survival during the first year following lung transplant . Following the implementation of the LAS score, the number of active wait list registrations was reduced by 50% and inactive registrations almost entirely eliminated. Five years prior to the implementation of the LAS score, 500 patients died waiting for lung transplants each year in the US. Following implementation of the LAS score, there was a significant decrease in wait list mortality by 40%, to an average of 300 deaths annually . A threefold increase in transplants was noted in intensive care unit patients, who prior to the LAS score may not have been transplanted for not having accrued sufficient time on the wait list . The LAS score does have its limitations. Data required for calculating recipient LAS scores is only derived from objective data collected by the OPTN and does not take into account subjective data. Lung transplant centers can apply to the UNOS Lung Review Board in situations where the calculated LAS score does not correlate with the patients’ condition in the hopes of amending the score to a higher one.

The US experience with LAS encouraged other countries to replace their older allocation systems. A LAS was introduced in Germany in 2011. In contrast to the USA, where distances are longer and allocation remained mainly local, the allocation is nationwide in Germany because of shorter distances. In both countries, the volume of transplantation increased after implementation of LAS, and fewer patients died on the waiting list . In addition, more patients with restrictive lung disease and significantly more critically ill patients received lung transplantation after implementation of the LAS in both countries .

Most recently, the UK lung transplant system has also introduced an urgency prioritization. Previously, patients were prioritized by individual transplant centers when a suitable donor became available primarily within regional zones. Patients who are rapidly deteriorating and requiring ECMO or NOVALUNG can now be registered for a super urgent or urgent lung transplant as part of a national list with access to suitable donors across the UK.