麻豆传媒

Choosing who with advanced heart failure (HF) gets a donor heart remains problematic in the U.S., according to a series of studies showing signals of gaming the rules and potentially poorer outcomes with left ventricular assist device (LVAD) destination therapy.

In 2018, the United Network for Organ Sharing (UNOS) reorganized its prioritization scheme for patients seeking donor hearts for transplantation, making those on temporary mechanical circulatory support (MCS) a high priority, for example, and keeping the high status of people on veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

But the imperfect prioritization system may have led to unintended consequences, according to two studies .

Since the new rules were implemented, patients with HF have been increasingly entering the waitlist on these temporary devices that make them status 1 candidates for donor hearts, one group found; another showed that durable LVADs have become less prevalent in patients waiting for a transplant.

While the waitlist rules are less unfavorable with an LVAD due to belief that these confer the same survival as heart transplant, survival actually was not equal between the two strategies in a separate report in the same journal.

More Temporary Mechanical Circulatory Support

Since people on temporary MCS started being prioritized for donor hearts in the U.S., transplant centers may have been incentivized to use devices like Impella and Tandemheart as a bridge to transplant in the cardiac ICU, according to a cohort study.

Records from medical cardiac ICU admissions showed that the proportion of patients with acute decompensated HF-related cardiogenic shock who were managed with temporary MCS was 25.4% from September 2017 to September 2018, the year before UNOS changed its donor heart allocation scheme.

That figure jumped to 42.6% in the period from October 2018 to September 2019 (P=0.004), the year immediately following the change, reported David Morrow, MD, MPH, of Brigham and Women's Hospital and Harvard Medical School, and colleagues.

After multivariable adjustment, people admitted to U.S. transplant hospitals in the post-revision period were found to be more likely to receive compared to before (adjusted OR 2.19, 95% CI 1.13-4.24).

No such temporal change in temporary MCS use was observed in non-transplant centers or Canadian centers (where donor heart allocation is dictated by a separate system).

"Of importance, our study complements prior data among orthotopic heart transplant recipients," Morrow's group said. "Because temporary MCS device use is resource intensive and associated with risks, the effect of increasing use on clinical outcomes will be important to delineate."

UNOS policy had been revised to give priority to people on nondischargeable MCS as they are the group with the highest waitlist mortality, study authors noted.

"Specifically, UNOS status 1 now includes patients supported with VA-ECMO or surgically implanted, nondischargeable MCS devices, and UNOS status 2 includes support with IABP or percutaneous MCS devices," according to the team.

The study was based on the Critical Care Cardiology Trials Network Registry and included 384 consecutive medical cardiac ICU admissions at seven U.S. transplant centers and seven non-transplant or Canadian centers.

Patients had to have cardiogenic shock due to ventricular failure; cases related to acute MI or after cardiotomy were excluded. Included patients averaged 61.2 years of age and 64.1% were men. Patient characteristics were stable between study periods, the authors reported.

The cohort study was limited by the relatively small sample and failed to capture transplant listing status among participants, they acknowledged.

Changes in Durable LVAD and VA-ECMO Listings, Too

Changing LVAD and VA-ECMO use raised concern about another type of gaming the change in organ allocation rules, according to a second group of researchers.

Since 2014, LVAD rates had been stable among adults newly listed for isolated heart transplant in the Organ Procurement and Transplantation Network (OPTN) registry operated by UNOS, Edo Birati, MD, of the Hospital of the University of Pennsylvania, Philadelphia, and colleagues found.

Yet after the October 2018 UNOS policy change pushing LVAD users to lower-priority tiers (because of improved waitlist survival with continuous-flow LVADs), the proportion of patients supported by these devices at listing abruptly started decreasing. The rate went from 35.1% in November 2018 to 24.5% in June 2019.

On the other hand, patients on VA-ECMO at listing -- who retained status 1 priority under the allocation system update -- increased from 1.2% to 3.2% during the same period immediately following rule implementation.

"These results suggest some exchangeability between initial support platforms, aligning with allocation incentives in spite of stringent listing criteria. These changes could be detrimental to if lower-acuity patients are prioritized for transplantation or if VA-ECMO support in the pretransplant period is itself directly harmful compared with LVAD," Birati's team warned in their research letter.

"A recalibration of the new allocation system may be required ... More data are required and urgently so," argued Clyde Yancy, MD, MSc, of Northwestern University Feinberg School of Medicine in Chicago, and Gregg Fonarow, MD, of the University of California Los Angeles, in an accompanying editor's note.

"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 wrote. "We must hold ourselves accountable to deploy VA-ECMO according to best clinical indications and to standardized data collection intended to identify better processes of care and reduce complications associated with VA-ECMO."

Birati and colleagues cautioned that their OPTN database analysis was retrospective in nature.

With more than 18,000 people included, however, "this database is the largest and most comprehensive database for heart transplants in the United States and as such represents all patients transplanted in the United States and the criteria used to justify their listing status," the authors maintained.

LVADs Not a Way Out of the Waitlist?

Finally, a study on the long-term survival of people with advanced HF showed that the strategy of destination-therapy LVAD was no substitute for getting on the heart transplant waitlist.

Patients who waited -- with or without bridge-to-transplant LVAD therapy -- had significantly better survival at 5 years compared with peers getting destination-therapy LVADs (RR 0.42, 95% CI 0.38-0.46), according to Donna Mancini, MD, of Mount Sinai Hospital in New York City, and collaborators.

This survival advantage was associated with actual receipt of a heart transplant (adjusted RR for time-dependent transplant status 0.27, 95% CI 0.24-0.32).

Waitlisted patients who did not undergo heart transplant had no better survival than patients receiving destination LVAD therapy in the retrospective propensity-matched cohort analysis linking the UNOS registry to the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS).

All age groups -- even 70- to 75-year-olds -- showed superior survival with the strategy of waiting for heart transplant.

"Continued improvement in LVAD technology, along with prospective comparative research, appears to be needed to amend this strategy," the investigators said.

"We recognize 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," according to Yancy and Fonarow.

Continuous-flow LVADs had been shown to offer at least 1- to 2-year survival, comparable to cardiac transplant, in literature cited by the authors.

Mancini's group identified 8,281 patients with advanced HF and formed 3,411 matched pairs between LVAD destination therapy and transplant waitlist groups.

Despite propensity score matching, destination-therapy LVAD recipients were still slightly older than those waitlisted for heart transplant (64.0 vs 60.0 years, P<0.001). However, there was no significant difference in sex (79.2% vs 77.6%, P=0.13).

Reliance on INTERMACS data meant the investigators were unable to completely capture reasons why some patients were deemed candidates for destination therapy versus bridge-to-transplant (BTT) LVADs. In addition, only LVADs on the U.S. market in 2010-2014 were included in the study, leaving out the newer HeartMate 3 pump.

"Furthermore, the linkage of the UNOS and INTERMACS data sets was only 67.7% complete, leaving patients with BTT for whom posttransplant outcomes were unknown," Mancini and colleagues acknowledged.

"Finally, in October 2018, the UNOS Allocation system with expansion to six statuses was implemented, and how this change may affect our findings is unclear," they added. "As patients with device malfunction, complications, or both increase in priority in the new system, it is unlikely that the results of the present analysis would be significantly changed."