This study evaluated the impact of MCS on heart transplant waiting list outcomes in an era of technological improvement and greater experience in the management of patients with VADs. The main finding of our study is the demonstration of markedly improved waiting list mortality and morbidity of heart transplant candidates bridged with durable LVADs in the current era. The mortality and morbidity risk in patients bridged with durable CF-LVADs is now similar to that in the status 2 listed patients (lowest priority). However, we also show that LVAD-supported transplant candidates whose status on the waiting list is upgraded as a result of an LVAD-related complication have a risk of mortality and mortality or delisting that is markedly higher compared with LVAD-supported candidates listed without complications and with status 2 listed patients. Interestingly, the proportion of patients who are listed in status 1A because of an LVAD-related complication is high and has remained without sig-nificant change between the 2 eras; 28% of LVAD-supported patients in the current era are listed in status 1A because of a device-related complication.
In the current era, the hazard of LVAD-related complications is highest early after listing for transplantation and nadirs at 80 days, after which it appears to again gradually increase (). Patients requiring biventricular support and temporary VADs continue to have a very high risk of adverse outcomes on the waiting list.
Since its inception, OPTN/UNOS has strived to maintain a fair and balanced organ allocation system by prioritizing organ allocation to patients with the highest risk of death while waiting for a donor organ. Our analyses from the first era confirm the pertinence of the indefinite 1B status listing afforded to the LVAD-bridged candidates by the UNOS policies at the time. The use of the first-generation PF-LVADs was associated with reduced mortality in heart transplant candidates with a very high risk of death and allowed these patients to reach heart transplantation. The risk of death or delisting of these LVAD-supported candidates remained significant, however, and our study shows that this risk was similar to that of status 1B candidates without MCS. Assessment of more recent outcomes shows that waiting list mortality of patients bridged with CF-LVADs after 2008 has decreased significantly and is below the waiting list mortality of status 1B candidates not supported with LVADs. In fact, the waiting list mortality of CF-LVAD–supported patients without serious LVAD-related complications now is similar to the mortality of low-urgency status 2 transplant candidates. The impact of improving outcomes in LVAD-supported transplant candidates on reducing the wait-list mortality has been important. For illustration, the overall waiting list mortality has decreased in recent years, and much of this effect was attributed to the broader organ regional sharing implemented by UNOS in 2006.26
It is likely, however, that LVAD use has also contributed significantly to this trend; our findings show that the reduction of waiting list mortality in LVAD-bridged patients in this time frame (4.1%/mo to 1.2%/mo, a 71% reduction) has been far larger than in patients without MCS (2.6%/mo to 2.3%/mo, a 12% reduction).
The improved waiting list survival of LVAD-supported candidates is a remarkable achievement that affords positive outcome to patients who would have been at a high risk of mortality in the past. Technological advances, expanding clinical experience with mechanical assist, and refined patient selection approaches have all contributed to the better outcomes and to the fact that more patients are now being considered for LVAD support.1,27
However, with these uniformly positive developments, we are also faced with a question of whether the current UNOS heart allocation algorithm remains equitable.15,28
Our data suggest that this question is multifaceted. For patients who require biventricular support and support with pulsatile or nondurable mechanical assist devices, the adverse outcomes on the waiting list remain high. Therefore, affording high-urgency status to these patients appears appropriate. The markedly improved wait-list mortality for patients bridged with CF-LVADs raises new considerations. Should the risk of mortality on the waiting list be the sole determinant of the allocation priority? If the answer is yes, then the current UNOS allocation system would appear to be outdated because patients with LVADs might have an advantage over patients at a higher risk of wait-list mortality, including those who may not be LVAD candidates. Along these lines, there have been suggestions to revise the UNOS allocation algorithm and possibly align it more closely with the Eurotransplant allocation system, which does not grant high-urgency status to LVAD-supported heart transplant candidates unless a device-related complication occurs.15,29
In contrast, our data indicate that this approach might not necessarily improve outcomes on the UNOS waiting list. LVAD implantation often transforms a sick patient at very high risk of wait-list and posttransplant mortality into a good transplant candidate with improved organ function and nutritional and physical condition, so transplant in this favorable situation may be of the most benefit. Our data show that almost 30% of LVAD-supported transplant candidates develop a complication that justifies a higher-urgency status listing and that, once this occurs, the risk of death or delist-ing is markedly increased. Some of these complications (eg, stroke) may also have long-lasting effects on patient quality of life after transplantation. If, as a result of a change in the organ allocation algorithm, LVAD-supported patients were to remain on the waiting list for a longer period of time, the cumulative incidence of device-related complications would likely increase (). Thus, the intent and the considerable expense that were dispensed to get an ill patient to transplant eligibility through the implantation of an LVAD could be negated, and the recent improvements in waiting list outcomes could be jeopardized.
Another consideration is that any organ allocation change is expected to result in changes in clinical decisions. It is conceivable that, if LVAD-supported patients were not given allocation priority, physicians and patients might opt to delay LVAD implantation for as long as possible in hopes of increasing the probability of receiving a heart transplant in high-urgency status on medical management. This, however, may expose the patients to higher risk of dying or becoming ineligible for transplantation (as our data for 1A and 1B status patients would suggest). In addition, those who decompensate on medical therapy may more likely require emergent LVAD implantation, increasing the risk profile of this group as well. These arguments would support continuation of the current allocation algorithm without change.
We recognize that there are limitations to our study. This was a retrospective analysis of a nationwide clinical registry. Although UNOS data collection is rigorous and undergoes periodic audits, some errors in data entry may be present. LVAD-specific morbidity outcomes and hospitalization data were not available and thus could not be contrasted with the morbidity outcomes and hospitalization rates of medically supported patients on the waiting list. Data on duration of LVAD support before registration on the waiting list were not available. Therefore, we were not able to accurately assess the effect of LVAD support duration on the risk of death. The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile for the patients in our study was not available; therefore, we were unable to explore the effects of this characteristic on evaluated outcomes. Some patients who were already active on the waiting list later received mechanical assist devices. We assigned these patients to the medical therapy group because that was the original intent at the time of listing. Patients who underwent VAD implantation but died or had significant complications precluding their relisting contributed to the primary and secondary outcomes of the medical treatment groups. Patients who were relisted for transplantation with an LVAD in the current era had an exceptionally good outcome: waiting list mortality rate of 0.74%/mo and mortality or delisting rate of 1.0%/mo. For completeness, we performed ancillary analyses with the group of patients requiring LVAD placement while already on the waiting list. We determined that this study group assignment did not change the results of the study (data not shown). Finally, the prevalence of conditions that would preclude LVAD implantation such as significant right ventricular dysfunction or certain forms of congenital heart disease could not be determined from this registry. We are aware that not all the questions raised can be answered by our study. Nevertheless, as an allocation change is being considered, we believe our analysis provides important insights that can help inform policy.