Patients with advanced heart failure — or at least a lucky few of them — have been receiving new hearts for more than 50 years, but many challenges and questions remain, which is why JAMA Cardiology is publishing three papers (two studies and a research letter) as well as an editorial addressing those issues.
In the editorial, JAMA Cardiology Deputy Editor Clyde W. Yancy, MD, MSc, Division of Cardiology at Northwestern University Feinberg School of Medicine, in Chicago, and JAMA Cardiology section editor Gregg C. Fonarow of the Ahmanson-UCLA Cardiomyopathy Center, at the David Geffen School of Medicine, UCLA, noted, “Today, 1-year survival after heart transplant is nearly 90%, and the conditional half-life after heart transplant is now 13 years.”
Yet, questions remain:
- Is use of a device for destination therapy a viable therapeutic option, or is it preferable to add patients to the transplant wait-list whether or not they receive a mechanical assist?
- A new schema for organ allocation was adopted in Oct. 2018, but does the new list really reallocate available donor organs to the patients in the greatest need?
- Is there a great variability among transplant centers?
The changes in allocation adopted by the Organ Procurement and Transplantation Network divided the category 1A into 3 categories and made status 1B category 4. It works like this: patients with LVADs and no device-related complications are now status 4 patients; patients with advanced heart failure and manageable LVAD complications are status 3 patients; status 2 patients have LVAD malfunctions or may be facing imminent death; and status 1 is reserved for patients “with life-threatening arrhythmias or patients being supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO).” Status 1 patients are at the top of the list.
In a research letter, Thomas C. Hanff, MD, MPH, of the Perelman School of Medicine at the University of Pennsylvania, and colleagues, looked at those new classifications to determine if donor organs were being matched to the neediest patients.
What they found were some curious changes in the percent of patients on LVADs, which had been pretty stable since 2014, and patients on VA-ECMO.
Prior to the new rules, 35.1% of waiting list patients were on LVADs, but by June 2019, that percent had dropped to 24.5%.
“Before rule publication, LVAD listings were increasing only 0.11% per month (95% CI, −0.007% to 0.2%; P = 0.07), and this slope decreased by only 0.10% after rule publication (95% CI, −0.32% to 0.12%; P = 0.37). After rule implementation, the slope decreased significantly by 1.44% per month compared with after publication (95% CI, −2.2% to −0.64%; P < 0.001),” Hanff and colleagues wrote. “Conversely, the percentage of patients supported by VA-ECMO at listing had been decreasing slightly during both preimplementation periods but began increasing significantly after rule implementation, from 1.2% in Nov. 2018 to 3.2% in June 2019. Before rule publication, VA-ECMO listings were decreasing 0.03% per month (95% CI, −0.06% to −0.009%; P = 0.008), and this slope was unchanged after rule publication (slope change, 0.04% per month; 95% CI, −0.01% to 0.09%; P = 0.17). After rule implementation, the slope increased significantly by 0.33% per month compared with after publication (95% CI, 0.10% to 0.56%; P = 0.005).”
Yancy and Fonarow noted that an earlier report by Cogswell et al suggested waiting list mortality improved after implementation of the new allocation system, “but a 4-fold increase in the use of VA-ECMO was observed after — compared with prior to — implementation… More data are required and urgently so. The greater use of VA-ECMO introduces a higher risk platform for circulatory support and identifies a more ill, if not desperately ill, population. Less good posttransplant outcomes should be expected.”
They pointed out that “Hanff and colleagues noted an abrupt increase in the use of VA-ECMO support that was temporally associated with implementation of the new system. Concomitantly, LVAD support for advanced heart failure in patients awaiting heart transplant abruptly decreased from 35.1% before implementation of the new rules to 24.5% after their implementation. Although the absolute use of VA-ECMO in June 2019 was 3.2% of patients awaiting transplant, it was 1.2% before rule implementation and is increasing at 0.33% per month. More research is needed to understand if there was a corresponding change in the level of acuity among patients awaiting transplant, but it is challenging to surmise such an abrupt change in acuity of individuals on the waiting list.”
In their JAMA Cardiology study, Anuradha Lala, MD, of the Icahn School of Medicine at Mount Sinai, New York City, New York, and colleagues compared survival rates for patients who were put on transplant waiting lists and implanted with LVADs — “bridge to transplant” patients — versus those who received LVADs as destination therapy.
They evaluated 3,411 patients listed for a transplant (prior to the new allocation system) supported with LVAD (bridge to transplant; n = 1,607) or without LVAD (n = 1,804) and compared outcomes to 3,411 propensity score-matched patients supported with LVAD destination therapy.
“The strategy of wait-listing for heart transplant was associated with better 5-year survival than LVAD destination therapy (risk ratio, 0.42; 95% CI, 0.38-0.46) after matching and adjusting for key clinical factors. This survival advantage was associated with heart transplant (adjusted risk ratio for time-dependent transplant status, 0.27; 95% CI, 0.24-0.32),” they wrote.
In an analysis of registry data funded by the National Institutes of Health, Ashley Y. Choi, BA, a student at the School of Medicine, Duke University, Durham, North Carolina, and colleagues looked at the variability in the acceptance of donor organs among transplant centers.
They evaluated data from 93 transplant centers that encompassed 19,703 donors and 9,628 candidates, of whom 32% were first-rank donors.
“After adjustment for donor, candidate, and geographic covariates, transplant centers varied in acceptance rates (12.3%-61.5%) of offers made to first-rank candidates. Higher acceptance rates were associated with lower cumulative incidence of 1-year mortality among patients on the wait-list,” they wrote. “For every 10% increase in adjusted center acceptance rate, the risk of mortality decreased by 27% (subdistribution hazard ratio, 0.73; 95% CI, 0.67-0.80). No statistically significant difference was observed in 5-year adjusted posttransplant patient survival (adjusted hazard ratio, 1.02; 95% CI, 0.94-1.11) and graft failure (subdistribution hazard ratio; 0.95; 95% CI, 0.83-1.09) between hearts accepted at the first-rank compared with lower-rank positions.”
In their editorial, Yancy and Fonarow acknowledged “the scarcity of donor hearts and the imperfectness of waiting-list strategies. The new allocation system was intended to provide greater access to those at highest risk, but the potential unforeseen consequence of less good posttransplant outcomes, if further substantiated, is sobering… Addressing center variability in donor acceptance rates and the consequent association with waiting-list mortality is an imminent opportunity worthy of further study. There is a need that we believe is urgent to understand the root causes of the wide variability in donor acceptance rates. Public reporting of acceptance rates may be a start.”
Finally, Yancy and Fonarow concluded that the “challenges outlined in this issue of JAMA Cardiology along with the early report by Cogswell et al warrant a revisit of that same ethos of discovery science and process improvement that solidified heart transplantation as a lifesaving treatment option. These are for certain significant challenges but no more difficult to address than the daunting challenges of the earlier eras that yielded the success we know today. The pressing need for more access to heart transplantation for stage D heart failure, the tenuousness of life for those awaiting a heart transplant, and the altruism of the donors and donor families require our redoubled commitment to make the next era of heart transplantation an even greater success.”
A study of 10-year data from transplant centers found an inverse relationship between the rate of acceptance of allografts and survival, so that for every 10% increase in adjusted center acceptance rate there was a 27% reduction in the rate of mortality among patients on the waitlist.
Patients with advanced heart failure have improved survival if they are placed on a heart transplant waiting list, regardless of the use of left-ventricular assist devices.
Peggy Peck, Editor-in-Chief, BreakingMED™
This study by Choi et al was funded by the Bollinger Scholarship Committee within the Department of Surgery at the Duke University Medical Center, the National Institutes of Clinical and Translational Science, and the National Center for Advancing Translational Sciences of the National Institutes of Health.
The study by Lala et al was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH), and the Canadian Institutes for Health Research.
The report from Hanff et al was supported by the National Institute of Health and the National Heart, Lung, and Blood Institute.
Choi reported receiving a grant from the National Institutes of Clinical and Translational Science of the National Institutes of Health during the study.
Lala had no disclosures.
Hanff reported grants from National Institute of Health/National Heart, Lung, and Blood Institute outside the submitted work.
Yancy reported spousal employment at Abbott Laboratories.
Fonarow reported receiving personal fees from Abbott Laboratories, Amgen, AstraZeneca, Bayer, CHF Solutions, Janssen, Medtronic, Merck & Co, and Novartis outside the submitted work.
Cat ID: 635
Topic ID: 97,635,570,730,634,192,925,635
Choi A Y, et al “Transplant center variability in organ offer acceptance and mortality among US patients on the heart transplant waitlist” JAMA Cardiol 2020; Published online April 15 DOI: 10.1001/jamacardio.2020.0659.
LaLa A, et al “Strategies of wait-listing for heart transplant vs durable mechanical circulatory support alone for patients with advanced heart failure” JAMA Cardiol 2020; Published online April 15 DOI: 10.1001/jamacardio.2020.0631.
Hanff TC, et al “Trends in mechanical support use as a bridge to adult heart transplant under new allocation rules” JAMA Cardiol 2020; Published online April 15 DOI: 10.1001/jamacardio.2020.0611.
Yancy CW, Fonarow GC “Anticipating a new era in heart transplantation” JAMA Cardiol 2020; Published online April 15 DOI: 10.1001/jamacardio.2020.0611.