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Impact of Temporary Percutaneous Mechanical Circulatory Support Before Transplantation in the 2018 Heart Allocation SystemFree Access

Clinical Research

J Am Coll Cardiol HF, 10 (1) 12–23
Sections

Central Illustration

Abstract

Objectives

This analysis sought to investigate the waitlist and post-transplant outcomes of individuals bridged to transplantation by using temporary percutaneous endovascular mechanical circulatory support (tMCS) through a status 2 designation (cardiogenic shock and exception).

Background

The 2018 donor heart allocation policy change granted a status 2 designation to patients supported with tMCS.

Methods

Adult patients in the United Network for Organ Sharing registry after October 18, 2018 who received a status 2 designation for tMCS were included and grouped by their status 2 criteria: cardiogenic shock with hemodynamic criteria (CS-HD), cardiogenic shock without hemodynamic criteria before tMCS (CS-woHD), and exception. Baseline characteristics, waitlist events (death and delisting), and post-transplant outcomes were compared.

Results

A total of 2,279 patients met inclusion criteria: 68.6% (n = 1,564) with CS-HD, 3.2% (n = 73) with CS-woHD, and 28.2% (n = 642) with exceptions. A total of 64.2% of patients underwent heart transplantation within 14 days of status 2 listing or upgrade, and 1.9% died or were delisted for worsening clinical condition. Among the 35.8% who did not undergo transplantation following 14 days, only 2.8% went on to receive a left ventricular assist device (LVAD). The 30-day transplantation likelihood was similar among groups: 80.1% for the CS-HD group vs 79.7% for the exception group vs 73.3% for the CS-woHD group; P = 0.31. However, patients who met criteria for CS-woHD had 2.3-fold greater risk of death or delisting (95% CI: 1.10-4.75; P = 0.03) compared with CS-HD patients after multivariable adjustment. Pre-tMCS hemodynamics were not associated with adverse waitlist events.

Conclusions

The use of tMCS is an efficient, safe, and effective strategy as a bridge to transplantation; however, patients with CS-woHD may represent a high-risk cohort. Transition to a durable LVAD was a rare event in this group.

Introduction

Allocation of organs to individuals in need of transplantation is governed by the United Network for Organ Sharing (UNOS), an organization that administers the Organ Procurement and Transplantation Network (OPTN) in the United States. On October 18, 2018, the OPTN heart allocation policy was modified with a stated goal of improving access to individuals with the greatest medical need through improved stratification of risk (1). Early reports demonstrated increased overall transplant volume, a broader distribution of donor hearts, improved stratification by medical urgency, and no significant change in waiting list or post-transplant survival (1). Following implementation of this policy, there has been a shift in the type of mechanical circulatory support (MCS) used. Before implementation of the policy, nearly 1 of 2 heart transplant recipients was supported with a durable left ventricular assist device (LVAD); however, after the policy change, that proportion decreased to 1 in 4 (2). There has been a commensurate increase in the use of temporary percutaneous endovascular MCS (tMCS) following the policy change, with more than 1 of 3 transplant recipients supported by tMCS (from ∼10%) (2).

Individuals with either a percutaneous endovascular MCS device (pMCS) or an intra-aortic balloon pump (IABP) receive status 2 designation if they meet defined cardiogenic shock criteria or are granted an exception. A study using the National Inpatient Sample before the 2018 allocation policy change suggested that individuals bridged to transplantation with tMCS (including extracorporeal membrane oxygenation [ECMO], an IABP, and percutaneous ventricular assist devices [Impella, Abiomed; and TandemHeart, LivaNova]) experienced increased complications (surgical reoperations, sepsis, bleeding complications, and acute organ injury) compared with non-tMCS recipients (3). This analysis sought to investigate the waitlist and post-transplant outcomes of individuals bridged to transplantation with tMCS (either pMCS or an IABP) through a status 2 designation (cardiogenic shock and exception).

Methods

The UNOS registry was used to ascertain all adult (aged ≥18 years), single-organ heart transplant candidates who received a status 2 designation between October 18, 2018 and September 4, 2020. Individuals were identified who received the status 2 designation for either pMCS (including Impella 2.5/CP/5.0/5.5 and TandemHeart devices) or an IABP. Included in the analysis were candidates who met the cardiogenic shock hemodynamic criteria (CS-HD group; systolic blood pressure <90 mm Hg, cardiac index <1.8 L/min/m2 if the candidate was not supported by inotropic agents or <2.0 L/min/m2 if the candidate was supported by inotropic agents, and pulmonary capillary wedge pressure [PCWP] >15 mm Hg within a 24-hour period), who were in cardiogenic shock without hemodynamic finding before tMCS criteria (CS-woHD group; cardiopulmonary resuscitation, systolic blood pressure <70 mm Hg, lactate >4.0 mmol/L, or aspartate aminotransferase or alanine aminotransferase >1,000 U/L), or who had exception criteria (candidate is admitted to the transplantation hospital and a transplant physician believes, using acceptable medical criteria, that a heart transplant candidate has an urgency and potential for benefit comparable to that of other candidates at the requested status, and the assigned UNOS regional review board approves).

Patients were classified into 3 groups according to the criteria used for tMCS status 2 designation: CS-HD, CS-woHD, and exception status. The primary outcome was the probability of heart transplantation. Secondary end points included death or delisting as a result of being too sick and the need for transition to a different form of MCS, post-transplant survival, and post-transplant length of stay. Six-month post-transplant survival was assessed, restricted to patients who underwent heart transplantation before March 3, 2020, to allow at least 6 months of follow-up and to mitigate influential censoring. Studies using this deidentified data set have been determined to be exempt from review by the Institutional Review Board of Columbia University Medical Center.

Statistical analysis

Demographic and clinical variables were expressed as mean ± SD for continuous normally distributed variables, median and IQR for variables with a non-normal distribution, and count (with percentage) for categorical variables. Group comparisons were performed using the Kruskal-Wallis test for continuous data and the chi-square test or Fisher exact test for categorical data where appropriate.

Given the competing events of transplant, death, and delisting while on the waitlist, cumulative incidence functions were calculated using the Gray test to compare the 2 study groups (4). Univariate and multivariable Fine and Gray subdistribution hazard models were generated to both account for competing risks and potential confounding covariates (5). The multivariable model included all covariates with a P < 0.20 during univariable analysis. Kaplan-Meier survival analysis was used for post-transplant survival, thus restricting the analysis to patients who had the opportunity to have 6 months of follow-up to avoid influential censoring. Receiver-operating characteristic curves were generated using logistic regression.

A 2-tailed P value of <0.05 was considered significant. Analyses were performed using SAS software version 9.4 (SAS Institute, Inc). Figures were created using SAS software version 9.4 and R software version 4.0.2 (R Foundation for Statistical Computing).

Results

During the study period, 2,279 patients received status 2 designation for an IABP (87.1%; n = 1,984) or pMCS (12.9%; n = 295) (Figure 1A). Among these, 68.6% (n = 1,564) met CS-HD criteria, 28.2% (n = 643) received exceptions, and 3.2% (n = 72) met CS-woHD criteria. Listing criteria varied among groups because a greater proportion of patients with an IABP met CS-HD criteria (69.8% vs 60.7%; P < 0.0001), nearly one-third of pMCS candidates required an exception compared with 27.7% of patients with an IABP (P < 0.0001), and more patients with pMCS were listed for CS-woHD (7.5% vs 2.5%; P < 0.0001). Among the groups, patients classified as Black represented a greater proportion of patients listed through exception criteria, and patients classified as Hispanic represented a greater proportion of patients listed for CS-woHD criteria (when compared with overall representation). Patients listed for CS-HD were more likely to have nonischemic cardiomyopathy and those listed for CS-woHD were more likely to have ischemic cardiomyopathy. Additionally, an estimated glomerular filtration rate <30 mL/min/1.73 m2 was more prevalent among those listed for CS-woHD (Table 1).

Figure 1
Figure 1

Distribution of tMCS

(A) Distribution of temporary percutaneous endovascular mechanical circulatory support (tMCS) device use in the new heart allocation system. Distribution of temporary percutaneous endovascular mechanical circulatory support devices used by (B) United Network for Organ Sharing UNOS region and (C) time period. IABP = Intra-aortic balloon pump.

Table 1 Baseline Characteristics

Cardiogenic Shock With Hemodynamics (n = 1,564)Cardiogenic Shock Without Hemodynamics (n = 72)Exception Status Criteria (n = 643)P Value
Male1,176 (75.2)56 (77.8)498 (77.5)0.49
Age, y56 (45-63)57 (48-64)57 (47-63)0.33
Ethnicity
 White916 (58.6)40 (55.6)352 (54.7)<0.001
 Black410 (26.2)12 (16.7)204 (31.7)
 Hispanic155 (9.9)16 (22.2)66 (10.3)
 Other83 (5.3)4 (5.5)21 (3.3)
Body mass index, kg/m226.7 (23.2-30.7)27.2 (23.2-30.3)27.5 (24.2-31.4)0.003
HF cause<0.0001
 Ischemic342 (21.8)25 (34.7)173 (26.9)
 Nonischemic1,109 (70.9)41 (56.9)387 (60.2)
 Restrictive or infiltrative67 (4.3)4 (4.2)40 (6.2)
 Retransplantation23 (1.5)2 (2.8)32 (5.0)
 Congenital23 (1.5)1 (1.4)11 (1.7)
Blood type0.77
 A549 (35.1)7 (37.5)235 (36.6)
 B261 (16.7)12 (16.7)89 (13.8)
 AB56 (3.6)2 (2.8)26 (4.0)
 O698 (44.6)31 (43.0)293 (45.6)
Temporary MCS<0.0001
 IABP1,385 (88.6)50 (69.4)549 (85.4)
 pMCS179 (11.4)22 (30.6)94 (14.6)
Cigarette use627 (40.1)24 (33.3)267 (41.5)0.39
ICD1,083 (71.5)44 (62.9)422 (67.9)0.10
Diabetes mellitus402 (26.6)23 (32.9)205 (33.0)0.009
Symptomatic cerebrovascular disease89 (5.7)7 (9.7)38 (5.9)0.36
Chronic kidney disease0.06
 GFR >60 mL/min/1.73 m2942 (60.4)40 (56.3)359 (56.1)
 GFR 30-60 mL/min/1.73 m2531 (34.0)23 (32.4)229 (35.8)
 GFR <30 mL/min/1.73 m287 (5.6)8 (11.3)52 (8.1)
Hemodynamics at listing
 PA systolic, mm Hg47 (38-56)45 (36-53)46 (35-56)0.04
 PA diastolic, mm Hg24 (19-30)22 (17-27)22 (17-28)<0.0001
 PA mean, mm Hg33 (26-39)31 (25-37)32 (24-38)0.001
 PCWP, mm Hg23 (18-28)22 (14-27)21 (15-26)<0.0001
 Cardiac index, L/min/m21.88 (1.58-2.33)2.19 (1.80-2.77)1.99 (1.63-2.41)<0.0001
Hemodynamics at status 2 upgrade
 Systolic blood pressure, mm Hg86 (82-88)
 PCWP, mm Hg25 (21-30)
 Cardiac index, L/min/m21.62 (1.41-1.80)

Values are n (%) or median (IQR).

GFR = glomerular filtration rate; HF = heart failure; IABP = intra-aortic balloon pump; ICD = implantable cardioverter-defibrillator; PA = pulmonary artery; PCWP = pulmonary capillary wedge pressure; pMCS = percutaneous endovascular mechanical circulatory support device; MCS = endovascular mechanical circulatory support.

The total number of patients designated as status 2 for IABP increased 21.6% from the first period (October 18, 2018 to April 7, 2019) to the second period (April 8, 2019 to September 27, 2019), and it remained relatively stable thereafter. Use of pMCS did not change between the first and second periods, but it increased 35.5% from the second period (April 8, 2019 to September 27, 2019) to the third period (September 28, 2019 to March 17, 2020). When analyzed by UNOS region, there was a general trend toward increased tMCS use after the first time period, although no changes were statistically significant overall (Figures 1B and 1C).

Overall, tMCS was an efficient and effective strategy to bridge patients to heart transplantation; among the patients who were listed as or upgraded to status 2 by using tMCS, 64.2% underwent transplantation within 14 days, and 80.1% underwent transplantation within 30 days. This strategy also resulted in a relatively low prevalence of adverse events when considering the patient’s clinical status; at 14 days, 1.9% had died or were delisted because they were too sick, and this percentage increased to 3.1% at 30 days. Comparing the study group with a contemporary group of patients with an LVAD before transplantation, the cumulative risk of an adverse event on the waitlist (death or delisting) was equivalent for the LVAD and tMCS groups (HR: 1.0; 95% CI: 0.78-1.28; P = 0.99) and the probability of transplantation was less for LVAD recipients (HR: 0.25; 95% CI: 0.23-0.27; P < 0.0001) (Supplemental Figure 1).

Comparing the outcomes of patients with tMCS by their criteria for status 2 designation, all groups had a similar probability of transplantation (exception vs CS-HD, HR: 0.95; 95% CI: 0.87-1.05; P = 0.31; CS-woHD vs CS-HD, HR: 0.83; 95% CI: 0.64-1.07; P = 0.15). Patients who met criteria for CS-woHD had 2.3-fold greater risk of death or delisting (95% CI: 1.12-4.81; P = 0.02) compared with CS-HD patients. The associated increased risk for CS-woHD was more attributable to the 3.9-fold increased risk of delisting (HR: 1.35-11.40; P = 0.01) than to the risk of death (HR: 1.58; 95% CI: 0.57-4.40; P = 0.38) (Supplemental Figure 2). There was no significant difference between individuals listed as having an exception or CS-HD (HR: 0.95; 95% CI: 0.64-1.41; P = 0.78) with respect to death or delisting (Figure 2). To account for baseline differences, multivariable adjustment was performed, and covariates associated with an increased chance of transplantation and death or delisting are listed in Table 2. The probability of transplantation was 12% lower (95% CI: 0.83-0.93; P < 0.0001) for an increase in body mass index by 5 kg/m2, was 30% lower for those with blood type O (95% CI: 0.64-0.77; P < 0.0001), and 11% lower for individuals identified as non-White (95% CI: 0.81-0.97; P = 0.008). The only risk factor that remained associated with an increased risk of death or delisting following multivariable adjustment was CS-woHD (HR: 2.28; 95% CI: 1.10-4.75; P = 0.03).

Figure 2
Figure 2

Transplant Waitlist Outcomes by Competing Risk Cumulative Incidence Function Curve Comparing Individuals Who Received UNOS Status 2 Designation Through tMCS Implantation

CS-HD = cardiogenic shock with hemodynamic criteria; CS-woHD = cardiogenic shock without hemodynamic criteria; other abbreviations as in Figure 1.

Table 2 Univariate and Multivariable Associations With the Risk of Transplantation and Death or Delisting

HR (95% CI)P ValueHR (95% CI)P Value
Transplantation
 Female0.94 (0.93-1.04)0.27
 Age (per 10 y)1.03 (1.00-1.07)0.061.00 (0.99-1.06)0.32
 Non-White0.84 (0.77-0.92)<0.00010.89 (0.81-0.97)0.008
 Body mass index (per 5 kg/m2)0.87 (0.83-0.92)<0.00010.88 (0.83-0.93)<0.0001
 Congenital0.90 (0.70-1.14)0.37
 Ischemic cardiomyopathy1.03 (0.93-1.14)0.59
 Restrictive or hypertrophic cardiomyopathy0.98 (0.84-1.15)0.84
 Retransplantation0.92 (0.71-1.19)0.52
 Cigarette use1.02 (0.93-1.11)0.71
 ICD0.98 (0.88-1.08)0.66
 Diabetes mellitus0.93 (0.85-1.03)0.190.99 (0.89-1.09)0.80
 Symptomatic cerebrovascular disease1.16 (0.97-1.39)0.101.17 (0.97-1.40)0.09
 Blood type O0.70 (0.64-0.77)<0.00010.70 (0.64-0.77)<0.0001
 CKD (GFR <60 mL/min/1.73 m2)1.06 (0.97-1.15)0.201.06 (0.971.16)0.23
 Hemodynamic criteria1.07 (0.97-1.17)0.181.03 (0.93-1.13)0.59
 Exception0.95 (0.87-1.05)0.31
 Nonhemodynamic criteria0.84 (0.64-1.07)0.150.84 (0.63-1.12)0.24
Death or delisting
 Female0.66 (0.41-1.05)0.080.69 (0.43-1.11)0.12
 Age (per 10 y)1.20 (1.00-1.30)0.051.20 (0.99-1.30)0.07
 Non-White1.08 (0.76-1.55)0.67
 Body mass index (per 5 kg/m2)1.10 (0.95-1.30)0.151.15 (0.99-1.30)0.16
 Congenital1.02 (0.25-4.13)0.98
 Ischemic cardiomyopathy1.02 (0.67-1.55)0.93
 Restrictive or hypertrophic cardiomyopathy0.98 (0.84-1.15)0.84
 Retransplantation0.92 (0.71-1.19)0.51
 Cigarette use0.97 (0.67-1.39)0.86
 ICD0.87 (0.59-1.27)0.46
 Diabetes mellitus1.13 (0.77-1.66)0.55
 Symptomatic cerebrovascular disease0.96 (0.45-2.10)0.92
 Blood type O1.24 (0.87-1.78)0.23
 CKD (GFR <60 mL/min/1.73 m2)1.19 (0.83-1.71)0.35
 Hemodynamic criteria0.89 (0.612-1.296)0.54
 Exception0.95 (0.64-1.41)0.78
 Nonhemodynamic criteria2.31 (1.12-4.81)0.022.28 (1.10-4.75)0.03

CKD = chronic kidney disease; other abbreviations as in Table 1.

To explore these differences further, we assessed the proportion of status 2 patients with tMCS who were upgraded to status 1 or transitioned to a higher level of MCS. Overall, 5.0% of the study cohort was upgraded to status 1, with no statistically significant differences among the 3 groups (Table 3). Similarly, the prevalence of transition to a different MCS device was 9.4% overall and not different among the groups (8.8% CS-HD vs 13.9% CS-woHD vs 10.3% exception; P = 0.24). Interestingly, only 2.8% of patients (2.8% CS-HD vs 1.4% CS-woHD vs 1.7% exception) ultimately received a durable LVAD. In a sensitivity analysis, we compared patients who met CS-woHD criteria with ECMO (status 1) vs tMCS (status 2; the criteria are the same for both groups) to assess whether patients who had tMCS may have had inadequate support. Both groups had a similar likelihood of transplantation (HR: 0.99; 95% CI: 0.74-1.33; P = 0.94), and although the comparison was underpowered, there was a suggestion of an increased risk of death or delisting for patients who underwent ECMO (HR: 1.57; 95% CI: 0.71-3.46; P = 0.27) and not for patients who had tMCS.

Table 3 Frequency of Individuals Requiring Status 1 Upgrade and Transition to Alternative Mechanical Circulatory Support Device

Cardiogenic Shock With Hemodynamics (n = 1,564)Cardiogenic Shock Without Hemodynamics (n = 72)Exception (n = 643)P Value
Status 1 upgrade87 (5.6)6 (8.3)22 (3.4)0.27
 ECMO54 (3.5)3 (4.2)11 (1.7)
 BiVAD15 (1.0)2 (2.8)3 (0.5)
 VT2 (0.1)1 (1.4)2 (0.3)
 Exception16 (1.0)0 (0.0)6 (0.9)
Device transition138 (8.8)6 (8.3)47 (7.3)0.51
 ECMO54 (3.5)3 (4.2)11 (1.7)
 BiVAD15 (1.0)2 (2.8)3 (0.5)
 Percutaneous RVAD4 (0.3)0 (0.0)2 (0.3)
 TandemHeart1 (0.1)0 (0.0)0 (0.0)
 Impella 5.018 (1.2)0 (0.0)11 (1.7)
 Impella CP2 (0.1)0 (0.0)2 (0.3)
 Durable LVAD44 (2.8)1 (1.4)18 (2.8)

Values are n (%).

BiVAD = biventricular assist device; ECMO = extracorporeal membrane oxygenation; LVAD = left ventricular assist device; RVAD = right ventricular assist device; VT = ventricular tachycardia.

Nearly two-thirds (1,564) of the cohort received status 2 designation by meeting hemodynamic criteria for cardiogenic shock. In this subgroup, preimplant hemodynamic findings were not predictive of transplantation or of death or delisting on the waitlist when treating systolic blood pressure, cardiac index, and PCWP as continuous variables (Figures 3A and 3B).

Figure 3
Figure 3

ROC Curves for Pre-tMCS Hemodynamics (Systolic BP, Cardiac Index, PCWP)

Prediction of (A) transplantation or (B) death or delisting. BP = blood pressure; PCWP = pulmonary capillary wedge pressure; Pre-tMCS = pre– temporary percutaneous endovascular mechanical circulatory support; ROC = receiver-operating characteristic.

There were no significant differences in early post-transplant survival at either 30 days (97.2% [95% CI: 96.1%-98.2%] CS-HD vs 95.5% [95% CI: 87.6%-99.6%] CS-woHD vs 97.4% [95% CI: 95.6%-98.8%] exception) or 6 months (94.4% [95% CI: 92.8%-95.8%] CS-HD vs 90.8% [95% CI: 80.6%-97.5%] CS-woHD vs 92.9% [95% CI: 90.0%-95.3%] exception; P = 0.34) (Figure 4). Post-transplant hospital length of stay was also similar among the groups (21.1 ± 19.0 days CS-HD vs 23.4 ± 21.7 days CS-woHD, 21.4 ± 16.3 days exception; P = 0.37).

Figure 4
Figure 4

Post-Transplant Survival Comparing Individuals Who Received UNOS Status 2 Designation Through tMCS Implantation

CS = cardiogenic shock; HD = hemodynamic criteria; other abbreviations as in Figure 1.

Discussion

The proportion of patients undergoing MCS as a bridge to transplantation has changed over the last 2 decades, increasing from <1 in 5 in 2000 to >1 in 2 in 2017 (6). The 2018 adult heart allocation policy change has shifted the type of MCS used, thereby decreasing the proportion of patients with durable MCS (eg, LVAD) and increasing the proportion supported with tMCS. The most common devices used include an IABP and pMCS. This study analyzed the outcomes of heart transplant candidates who received a status 2 designation for tMCS and yielded several notable findings (Central Illustration):

1.

A total of 64.2% of patients who were upgraded to status 2 and were using tMCS underwent transplantation within 14 days and 80.1% within 30 days.

2.

Preimplant hemodynamic findings were not associated with the probability of death or delisting on the waitlist.

3.

Patients in the exception group had outcomes indistinguishable from those of patients with CS-HD.

4.

Even though more than one-third of patients were still waiting for transplantation after 2 weeks, only 2.8% transitioned to a durable LVAD.

5.

Patients listed for CS-woHD had a 2.3-fold greater risk of death or delisting compared with patients with CS-HD.

Central IllustrationCentral Illustration
Central Illustration

Pre- and Post-Transplant Outcomes of Individuals Listed as UNOS Status 2 Designation With Temporary Mechanical Circulatory Support

Patients with a status 2 designation resulting from a temporary percutaneous mechanical circulatory support device had a high likelihood of transplantation (80.1% within 30 days), and patients with cardiogenic chock without hemodynamics before temporary percutaneous endovascular mechanical circulatory support had a greater risk of adverse events on the waitlist. Post-transplant survival was similar, and few patients transitioned to a durable left ventricular assist device. CS = cardiogenic shock; CS-HD = cardiogenic shock with hemodynamic criteria; CS-woHD = cardiogenic shock without hemodynamic criteria; LVAD = left ventricular assist device; PCWP = pulmonary capillary wedge pressure; tMCS = temporary percutaneous endovascular mechanical circulatory support; UNOS = United Network for Organ Sharing.

One of the stated goals of the 2018 revision to the U.S. adult heart allocation policy was to “modernize prioritization based on the predicted waiting list mortality or candidates’ medical urgency” (1). Early analyses demonstrated that the new 6-tiered system provided improved waitlist risk stratification between each status. The current analysis focused on patients who received a status 2 designation through tMCS implantation, grouped by the criteria that they fulfilled. The risk of adverse events while on the waitlist differed depending on the indication for status 2. First, for the one-fourth of the cohort who received a status 2 designation through an exception, the risk of death or delisting on the waitlist was indistinguishable from the risk for individuals who met hemodynamic criteria for cardiogenic shock. These findings suggest that listing physicians and regional review boards are identifying patients at risk who would not have otherwise met criteria for status 2, and these patients have a waitlist mortality risk similar to that of patients meeting CS-HD criteria, but lower than those with CS-woHD. These data, when considered along with the hemodynamic findings, hint that at least some individuals who meet CS-HD criteria are not as acutely at risk as initially thought. The small proportion of individuals who received a status 2 designation for meeting CS-woHD criteria had more than twice the risk of death or delisting as the other 2 groups. This finding suggests that those criteria (cardiopulmonary resuscitation, systolic blood pressure <70 mm Hg, lactate >4.0 mmol/L, or aspartate aminotransferase or alanine aminotransferase >1,000 U/L) can help identify patients meriting prioritization. Subjectively, few would disagree that patients who fulfill status 2 CS-woHD criteria are likely to be more acutely ill than the other 2 groups; nevertheless, they receive the same priority status. Although some of this risk may be the result of individual patient management, it does put forward that the CS-woHD group warrants greater priority on the waitlist, and incorporation of biomarkers of organ hypoperfusion (elevated lactate, acute kidney injury, ischemic hepatitis) may help provide greater differentiation of patients with the greatest risk of waitlist mortality.

In the previous allocation system, a strategy of LVAD as a bridge to transplantation was common (∼45%) (7) and necessary in that status 1A wait time could range from about a week to more than 2 months, depending on blood type and UNOS region (8). This situation has changed with implementation of the 2018 allocation policy because broader sharing of donor hearts and higher priority statuses for individuals meeting specific criteria allow those individuals frequently to bypass durable MCS on their way to heart transplantation. The policy specified, however, that if an individual did not receive a heart transplant within 2 weeks, and did not have a contraindication to LVAD, that individual should proceed to LVAD surgery or be downgraded to status 3. During the study period, 35.8% of individuals remained on tMCS support following 2 weeks of status 2 designation; however, only 2.8% of these patients ended up receiving an LVAD. Initially, what constituted a contraindication to LVAD was not defined, although since March 4, 2021, there has been an official guidance document from the OPTN Network specifying what constitutes a contraindication to LVAD, noting that, “It is recommended that requesting programs not rely solely on patient preference when submitting an extension exception request to maintain a candidate at Status 2.” Patient and physician preference to go directly to transplantation, thereby avoiding additional surgery (LVAD implantation), the risk of complications following LVAD implantation before future transplant surgery, and the prolonged waitlist time that LVAD recipients face in the current system likely explain the small number of patients who transitioned to LVAD in this cohort. Moreover, although the current allocation policy allows patients to avoid an LVAD (80.1% underwent transplantation within 30 days), patients are exposed to longer intensive care unit courses with tMCS and potential infectious, bleeding, and vascular complications that may affect post-transplant outcomes, including length of hospitalization and survival.

One of the important components of the 2018 allocation policy change was defining cardiogenic shock with hemodynamic criteria. Previously there was no codified UNOS definition of cardiogenic shock, and the current criteria are easily measured and generalizable. However, in this study cohort, none of the pre-tMCS hemodynamic criteria were predictive of waitlist adverse events. This was thought provoking given the wide hemodynamic ranges that existed among this patient cohort, and it suggests that systolic blood pressure, cardiac index, and PCWP are not sufficient discriminators of disease severity. Subsequent to implementation of the new allocation policy, the Society for Cardiovascular Angiography and Interventions Classification of Cardiogenic Shock was proposed, creating a schema with 5 stages of shock incorporating biomarkers, physical examination, and hemodynamic values (9). The challenge in determining the best definition of cardiogenic shock for heart transplantation listing criteria lies in that our patients differ greatly. For instance, a subset of patients are ambulatory, yet they meet cardiogenic shock hemodynamic criteria. These patients display long-term adaptions to heart failure that allow them to maintain adequate end-organ perfusion despite chronically elevated filling pressures and low outputs, whereas the same hemodynamic features are often poorly tolerated in patients with acute heart failure who lack such adaptations resulting in significant end-organ dysfunction. Although functional testing (eg, peak exercise oxygen consumption), which was more prognostic than cardiac index or PCWP (10), may provide greater discrimination, it is often impractical for these patients. Data from this study infer that incorporation of biomarkers of organ hypoperfusion (elevated lactate, acute kidney injury, ischemic hepatitis) could provide greater discrimination of patients with the greatest risk of waitlist mortality. However, although implementation of a more restrictive criteria may identify higher-risk individuals, it increases the possibility of excluding patients who may not fulfill all criteria, yet the treating physicians believe merit an elevated priority status, and thus may further expand the exception group (11).

One finding of this study that, albeit not the focus, warrants mention was that non-White individuals were less likely to undergo heart transplantation. This finding persisted following multivariable adjustment, yet it was not attributable to the risk of death or delisting. Further examination of this finding is needed.

Study limitations

The first of this study’s limitations is that although the UNOS data set used for this analysis is of high quality in that for all U.S. transplant centers data submission is mandatory by law, the data are subject to reporting inaccuracies and are limited to the data available for analysis. Second, the causes of adverse waitlist events (death or delisting) were not available. Third, post-transplant survival was limited to patients who were at least 6 months post-transplant to avoid influential censoring; however, this also limited analysis of the full cohort. Finally, the 2018 allocation policy remains in its infancy, and we recognize that practice patterns may have evolved during the study period.

Conclusions

The use of tMCS is a safe, effective, and efficient method to bridge patients to transplantation in the new heart allocation system. Patients listed using CS-woHD criteria have an increased risk of adverse waitlist events and may benefit from greater prioritization. Finally, pre-tMCS hemodynamic findings are not predictive of transplantation or death or delisting among patients who undergo tMCS.

Perspectives

COMPETENCY IN MEDICAL KNOWLEDGE: Patients supported listed for heart transplantation as “status with temporary MCS” have a high likelihood of transplantation (80.1% after 30 days) and a low risk of death or delisting (3.1% after 30 days).

TRANSLATIONAL OUTLOOK: Hemodynamic findings (systolic BP, cardiac index, PCWP) before temporary percutaneous endovascular mechanical circulatory support were not predictive of transplantation or adverse events. Further study is needed to identify criteria to best risk stratify patients awaiting heart transplantation.

Funding Support and Author Disclosures

Dr Clerkin is supported by National Heart, Lung and Blood Institute grant K23 HL148528. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Abbreviations and Acronyms

ECMO

extracorporeal membrane oxygenation

IABP

intra-aortic balloon pump

LVAD

left ventricular assist device

OPTN

Organ Procurement and Transplantation Network

PCWP

pulmonary capillary wedge pressure

pMCS

percutaneous endovascular mechanical circulatory support device

tMCS

temporary percutaneous endovascular mechanical circulatory support

UNOS

United Network for Organ Sharing

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Footnotes

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.