Abstract
Background.
The 2018 heart allocation change has resulted in greater frequency of high-risk bridging to orthotopic heart transplantation (OHT). Although survival has been studied in these patients, functional status outcomes are less established. This study evaluated changes in functional status of OHT survivors based on bridging strategy.
Methods.
Adults (≥18 y) undergoing OHT between January 2015 and March 2020 were stratified by bridging modality: no bridging, inotropes only, intra-aortic balloon pump (IABP), temporary ventricular assist device (VAD), durable VAD, and extracorporeal membrane oxygenation (ECMO). Using paired analysis, the Karnofsky performance scale (0–100) was utilized to compare differences in function at listing, transplant, and follow-up.
Results.
In total, 13 142 patients underwent OHT. At the time of both listing and transplant, patients requiring IABP, temporary VAD, and ECMO displayed the lowest functional status (each median 20) compared with other groups (P < 0.001). Among survivors, the median performance status at follow-up was ≥80 for all groups, indicating total functional independence with no assistance required. Substantial improvement in Karnofsky score occurred from transplant to follow-up in survivors bridged with IABP (40), temporary VADs (60), and ECMO (50) (each P < 0.001). Among survivors with at least 90-day follow-up, the median Karnofsky score was 90 regardless of bridging modality.
Conclusions.
Despite a higher mortality risk, critically ill patients who survive OHT after bridging with high-risk modalities experience acceptable functional status outcomes. These findings are important to place in the context of the impact that the 2018 allocation change has had on the landscape of OHT in the United States.
INTRODUCTION
Orthotopic heart transplantation (OHT) is a leading treatment option for patients with end-stage heart failure yet is limited by organ availability. As such, significant effort has focused on outcomes following OHT to maximize survival and identify patients with the greatest potential for benefit posttransplant. Prior studies have explored survival following OHT, particularly in patients bridged with mechanical circulatory support (MCS) devices.1–3 The 2018 United Network for Organ Sharing (UNOS) allocation policy change shifted the profile of patients undergoing OHT with prioritization of patients requiring higher levels of support including extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP) support.4,5 Recent reports have suggested that although overall waitlist outcomes have improved with this policy change, posttransplant survival has declined primarily due to the higher risk nature of recipients being transplanted.4,6 Although some groups have expressed concern regarding these findings, what is less understood are the functional status outcomes of these higher risk patients, which can impact quality of life and be an important metric in evaluating transplantation outcomes.7,8 This study evaluated changes in functional status in patients bridged to OHT with different bridging modalities.
MATERIALS AND METHODS
Study Cohort
Utilizing the UNOS database, we explored adult patients (≥18 y) undergoing OHT between January 1, 2015, and March 20, 2020. Patients undergoing multiorgan transplants (eg, heart-lung, heart-kidney) were excluded. Patients were stratified into 6 groups based on bridging modality: no bridging, inotropes only, IABP, temporary ventricular assist device (VAD), durable VAD, and extracorporeal membrane oxygenation (EMCO). Patients requiring support with inotropes and MCS were grouped with their MCS device. For patients requiring support with >1 MCS device, patients were grouped with the highest level of support (ie, ECMO if ECMO with IABP, ECMO if ECMO with VAD, VAD if IABP with VAD). The temporary VAD group included patients bridged with a Centrimag, Rotaflow, or Impella device. Support device was considered at the time of transplant.
Functional status was obtained utilizing the Karnofsky score, which is a validated measure of performance status on a scale from 0 to 100 with 0 being dead and 100 being fully functional (Table S1, SDC, http://links.lww.com/TP/C94).9 Functional status data were available at the time of listing, at the time of transplant, and at the most recent follow-up. These data are not recorded at specified time intervals, and the status is evaluated and recorded by trained providers at each transplant center. As previously validated and described, Karnofsky scores of ≥80 indicate total functional independence with no special assistance required. A sub-analysis was conducted exploring only those patients who were alive at the most recent follow-up.
Statistical Analysis
Continuous data are reported as mean (SD) for Gaussian data and median (interquartile range, IQR) for non-Gaussian data. Categorical data are reported as number (percentage). Comparison of baseline characteristics among the groups was performed using 1-way ANOVA and Kruskal-Wallis testing for Gaussian and non-Gaussian data, respectively. Chi-square testing was utilized for categorical data. For paired analysis of changes in functional status at different time points, paired t-testing and Wilcoxon signed rank testing were utilized. Kaplan-Meier analysis was utilized to compare 1-year survival stratified by bridging modality with log-rank testing used to compare survival curves. Missingness for each of the functional status time points (ie, at list, at transplant, at follow-up) was 3.82%, 7.11%, and 22.86%. Missing data were not imputed. All hypothesis testing was 2-sided. Statistical analyses were performed using the Stata 16 software package (StataCorp, 2017, Stata Statistical Software: Release 16, College Station, TX). This study was approved by the Institutional Review Board at the University of Pittsburgh.
RESULTS
Description of the Study Population
A total of 13 412 patients underwent OHT with the following stratification by bridging modality: no bridging (N = 2,420, 18.04%), inotropes only (N = 3,032, 22.16%), IABP (N = 1,628, 12.14%), temporary VAD (N = 235, 1.75%), durable VAD (N = 5,823, 43.42%), and ECMO (N = 274, 2.04%) (Table 1). Recipient characteristics were significantly different between the groups, including age, sex distribution, laboratory values, and causes of heart failure. Additionally, donor characteristics, days on the waitlist, and organ ischemic time varied based on bridging modality.
TABLE 1.
Baseline characteristics of patients undergoing orthotopic heart transplantation, stratified by bridging modality
| No bridging N = 2420 18.04% | Inotropes N = 3032 22.61% | IABP N = 1628 12.14% | Temporary VAD N = 235 1.75% | Durable VAD N = 5823 43.42% | ECMO N = 274 2.04% | P | ||
|---|---|---|---|---|---|---|---|---|
| Recipient | ||||||||
| Age (y)—median (IQR) | 56 (45, 63) | 57 (46, 64) | 57 (48, 63) | 53 (38, 61) | 55 (46, 62) | 49 (33, 58) | <0.001 | |
| Male sex—no. (%) | 1537 (63.51) | 2046 (67.48) | 1199 (73.65) | 179 (76.17) | 4626 (79.44) | 198 (72.26) | <0.001 | |
| Race—no. (%) | <0.001 | |||||||
| -White | 1634 (67.80) | 1913 (63.47) | 1021 (62.95) | 146 (62.93) | 3667 (63.29) | 187 (68.75) | ||
| -Black | 417 (17.30) | 644 (21.37) | 389 (23.98) | 40 (17.24) | 1462 (25.23) | 49 (18.01) | ||
| -Hispanic | 253 (10.50) | 299 (9.92) | 149 (9.19) | 32 (13.79) | 460 (7.94) | 18 (6.62) | ||
| -Other | 106 (4.40) | 158 (5.24) | 63 (3.88) | 14 (6.03) | 205 (3.54) | 18 (6.62) | ||
| BMI (kg/m2)—mean (SD) | 27.29 (4.85) | 26.64 (4.77) | 26.55 (4.74) | 26.61 (5.02) | 28.88 (4.82) | 26.96 (5.14) | 0.445 | |
| Creatinine (mg/dL)—median (IQR) | 1.12 (0.90, 1.40) | 1.19 (0.93, 1.47) | 1.13 (0.90, 1.40) | 1.06 (0.81, 1.40) | 1.20 (0.97, 1.44) | 1.00 (0.70, 1.50) | <0.001 | |
| Bilirubin (mg/dL)—median (IQR) | 0.60 (0.40, 1.00) | 0.70 (0.50, 1.10) | 0.77 (0.50, 1.20) | 0.90 (0.60, 1.70) | 0.60 (0.40, 0.90) | 1.10 (0.70, 2.00) | <0.001 | |
| Diabetes—no. (%) | 544 (22.48) | 835 (27.54) | 444 (27.27) | 58 (24.68) | 1786 (30.67) | 53 (19.34) | <0.001 | |
| Cause of heart failure—no. (%) | <0.001 | |||||||
| -Nonischemic cardiomyopathy | 1004 (41.49) | 1532 (50.53) | 905 (55.59) | 128 (54.47) | 3477 (59.71) | 130 (47.45) | ||
| -Ischemic cardiomyopathy | 650 (26.86) | 821 (27.08) | 457 (28.07) | 75 (31.91) | 2024 (34.76) | 64 (23.36) | ||
| -Congenital | 128 (5.29) | 181 (5.97) | 36 (2.21) | 3 (1.28) | 39 (0.67) | 6 (2.19) | ||
| -Valvular | 23 (0.95) | 56 (1.85) | 21 (1.29) | 1 (0.43) | 44 (0.76) | 9 (3.28) | ||
| -Hypertrophic cardiomyopathy | 161 (6.65) | 121 (3.99) | 54 (3.32) | 3 (1.28) | 55 (0.94) | 8 (2.92) | ||
| -Restrictive cardiomyopathy | 154 (6.36) | 185 (6.10) | 83 (5.10) | 8 (3.40) | 58 (1.00) | 14 (5.11) | ||
| -Failed primary heart transplant | 125 (5.17) | 69 (2.28) | 40 (2.46) | 8 (3.40) | 12 (0.21) | 29 (10.58) | ||
| -Other/Unknown | 175 (7.23) | 67 (2.21) | 32 (1.97) | 9 (3.83) | 114 (1.96) | 14 (5.11) | ||
| Mechanical ventilation—no. (%) | 155 (7.33) | 241 (7.97) | 240 (14.81) | 89 (38.36) | 1534 (26.59) | 168 (61.54) | <0.001 | |
| ICU before transplant—no. (%) | 590 (27.74) | 1367 (45.09) | 1539 (94.71) | 217 (92.74) | 542 (9.31) | 259 (94.53) | <0.001 | |
| Donor | ||||||||
| Age (years)—median (IQR) | 32 (24, 41) | 32 (23, 42) | 30 (23, 39) | 31 (23, 39) | 30 (23, 39) | 33 (24, 40) | <0.001 | |
| Male sex—no. (%) | 1508 (62.31) | 1905 (62.83) | 1183 (72.67) | 169 (71.91) | 4430 (76.08) | 203 (74.09) | <0.001 | |
| Race—no. (%) | <0.001 | |||||||
| -White | 1547 (64.70) | 1918 (64.02) | 1004 (62.01) | 131 (56.47) | 3867 (66.79) | 185 (67.77) | ||
| -Black | 356 (14.89) | 470 (15.69) | 294 (18.16) | 39 (16.81) | 952 (16.44) | 43 (15.75) | ||
| -Hispanic | 428 (17.90) | 531 (17.72) | 284 (17.54) | 51 (21.98) | 842 (14.54) | 38 (13.92) | ||
| -Other | 60 (2.51) | 77 (2.57) | 37 (2.29) | 11 (4.74) | 129 (2.23) | 7 (2.56) | ||
| Mechanism of death—no. (%) | <0.001 | |||||||
| -Trauma | 962 (39.75) | 1300 (42.88) | 724 (44.47) | 97 (41.28) | 2682 (46.06) | 136 (49.64) | ||
| -CVA | 388 (16.03) | 591 (19.49) | 243 (14.93) | 47 (20.00) | 878 (15.08) | 28 (10.22) | ||
| -Natural causes | 483 (19.96) | 533 (17.58) | 294 (18.06) | 38 (16.17) | 994 (17.07) | 51 (18.61) | ||
| -Other | 587 (24.26) | 608 (20.05) | 367 (22.54) | 53 (22.55) | 1269 (21.79) | 59 (21.53) | ||
| BMI (kg/m2)—mean (SD) | 27.31 (6.26) | 27.52 (6.42) | 27.44 (5.96) | 28.22 (5.77) | 28.00 (6.07) | 27.39 (6.10) | 0.001 | |
| Diabetes—no. (%) | 100 (4.16) | 12 (4.08) | 50 (3.09) | 9 (3.86) | 211 (3.64) | 3 (1.10) | 0.090 | |
| Recipient-donor matching | ||||||||
| Sex-matched—no. (%) | 1815 (75.00) | 2231 (73.58) | 1244 (76.41) | 179 (76.17) | 4707 (80.83) | 207 (75.55) | <0.001 | |
| Race-matched—no. (%) | 1271 (52.52) | 1495 (49.31) | 784 (48.16) | 106 (45.11) | 3037 (52.16) | 147 (53.65) | 0.003 | |
| HLA-matched—no. (%) | 2152 (97.24) | 2725 (96.53) | 1457 (96.88) | 183 (95.81) | 4966 (96.65) | 235 (96.31) | 0.692 | |
| ABO-matched—no. (%) | 2071 (85.58) | 2527 (83.34) | 1325 (81.39) | 178 (75.74) | 5235 (89.90) | 202 (73.72) | <0.001 | |
| CMV matched—no. (%) | 923 (38.38) | 1099 (36.51) | 611 (37.69) | 87 (37.34) | 2363 (40.76) | 111 (40.66) | 0.004 | |
| Transplant | ||||||||
| Days on waitlist—median (IQR) | 61 (19, 190) | 50 (18, 146) | 22 (8, 70) | 22 (7, 64) | 209 (70, 480) | 7 (3, 21) | <0.001 | |
| Ischemic time (hours)—median (IQR) | 3.10 (2.33, 3.77) | 3.10 (2.35, 3.73) | 3.38 (2.75, 3.93) | 3.30 (2.60, 3.88) | 3.13 (2.37, 3.77) | 3.35 (2.68, 3.87) | <0.001 | |
BMI, body mass index; CMV, cytomegalovirus; CVA, cerebrovascular accident; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; ICU, intensive care unit; VAD, ventricular assist device.
Analysis of Functional Status
At the time of listing, mean functional status was lowest in patients requiring ECMO (25.86) with patients requiring IABP (mean 34.53) and temporary VADs (mean 32.11) also displaying functional status scores in the lower range (Table 2). Similar patterns were observed at the time of transplant. At follow-up, mean scores remained lowest among patients requiring ECMO, IABP, and temporary VAD at the time of transplant.
TABLE 2.
Functional status at the time of listing, transplant, and last follow-up in patients undergoing orthotopic heart transplantation, stratified by bridging modality
| No bridging | Inotropes | IABP | Temporary VAD | Durable VAD | ECMO | p | ||
|---|---|---|---|---|---|---|---|---|
| At listing | Mean (SD) | 51.52 (20.98) | 45.30 (20.58) | 34.53 (19.59) | 32.11 (21.56) | 50.54 (21.56) | 25.86 (18.49) | <0.001 |
| Median (IQR) | 50 (40, 70) | 40 (30, 60) | 20 (20, 50) | 20 (20, 40) | 50 (30, 70) | 20 (20,20) | <0.001 | |
| At transplant | Mean (SD) | 46.83 (21.64) | 35.78 (19.53) | 22.91 (12.13) | 24.20 (16.69) | 52.98 21.18) | 21.67 (17.59) | <0.001 |
| Median (IQR) | 50 (30, 70) | 30 (20, 50) | 20 (20, 20) | 20 (20, 20) | 50 (40, 70) | 20 (10, 20) | <0.001 | |
| At follow-up | Mean (SD) | 79.24 (24.87) | 82.43 (24.14) | 63.44 (33.89) | 63.47 (33.96) | 79.88 (24.39) | 52.05 (37.75) | <0.001 |
| Median (IQR) | 90 (70, 100) | 90 (80, 100) | 80 (20, 90) | 80 (20, 90) | 90 (70, 100) | 40 (20, 90) | <0.001 | |
ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; IQR, interquartile range; VAD, ventricular assist device.
When comparing functional status changes from the time of listing to transplant, mean scores decreased significantly in all groups except for patients bridged with durable VAD (mean increase 2.66, P < 0.001) (Table 3). Mean and median follow-up for the overall cohort was 655.25 and 640 days, respectively. Between listing or transplant and the most recent follow-up, functional scores increased significantly in all groups (all P < 0.001 by paired analysis). Patients requiring inotropes only demonstrated the greatest increase in mean functional status score between transplant and follow-up (mean 46.51, P < 0.001), whereas patients with a durable VAD displayed the lowest increase (mean 25.87, P < 0.001). The percentage of recipients who were functionally independent at listing and at follow-up, stratified by bridging modality, is also shown (Figure 1). At last follow-up, 63.95% bridged with inotropes were considered functionally independent compared with 61.36% bridged with durable VADs, 48.06% with no bridging, 39.56% with IABP, 35.74% with temporary VADs, and 30.29% with ECMO.
TABLE 3.
Differences in functional status scores in patients undergoing orthotopic heart transplantation, stratified by bridging modality
| No bridging | Inotropes | IABP | Temporary VAD | Durable VAD | ECMO | p | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Difference | p | Difference | p | Difference | p | Difference | p | Difference | p | Difference | p | |||
| Listing to transplant | Mean (SD) | −4.93 (21.27) | <0.001 | −9.47 (19.73) | <0.001 | −11.29 (20.17) | <0.001 | −7.55 (20.01) | <0.001 | 2.66 (23.28) | <0.001 | −4.17 (20.76) | 0.002 | <0.001 |
| Median (IQR) | 0 (−10, 0) | <0.001 | 0 (−20, 0) | <0.001 | 0 (−20, 0) | <0.001 | 0 (−10, 0) | <0.001 | 0 (−10, 10) | <0.001 | 0 (−10, 0) | <0.001 | <0.001 | |
| Transplant to follow-up | Mean (SD) | 31.23 (30.02) | <0.001 | 46.51 (29.74) | <0.00 | 39.46 (34.47) | <0.001 | 39.72 (35.42) | <0.001 | 25.87 (28.08) | <0.001 | 30.65 (36.93) | <0.001 | <0.001 |
| Median (IQR) | 30 (0, 60) | <0.001 | 50 (30, 70) | <0.001 | 60 (0, 70) | <0.001 | 60 (0, 70) | <0.001 | 30 (0, 50) | <0.001 | 0 (0, 70) | <0.001 | <0.001 | |
| Listing to follow-up | Mean (SD) | 25.96 (30.17) | <0.001 | 36.92 (30.55) | <0.001 | 27.89 (38.90) | <0.001 | 32.54 (37.39) | <0.001 | 29.22 (31.04) | <0.001 | 26.43 (42.57) | <0.001 | <0.001 |
| Median (IQR) | 30 (10, 50) | <0.001 | 40 (20, 60) | <0.001 | 30 (0, 60) | <0.001 | 35 (0, 70) | <0.001 | 30 (10, 50) | <0.001 | 10 (0, 70) | <0.001 | <0.001 | |
ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; IQR, interquartile range; VAD, ventricular assist device.
FIGURE 1.
Percentage of recipients with a Karnofsky performance status ≥80, stratified by bridging modality. Functional status is shown at the time of listing and at last follow-up. ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; VAD, ventricular assist device.
Analysis in Patients Who Were Alive at Follow-up
A total of 11 473 patients were alive at their most recent follow-up, with a mean and median follow-up of 700.91 and 715 days, respectively (Table S2, SDC, http://links.lww.com/TP/C94). At the time of listing, functional status was highest in patients requiring no bridging (mean 51.80) and those bridged with a durable VAD (mean 50.68) and lowest in patients requiring ECMO (mean 25.75) (Table S3, SDC, http://links.lww.com/TP/C94). At follow-up, mean functional status was ≥80 for patients not requiring bridging, those requiring inotropes only, and those patients bridged with a durable VAD. Significant improvement from listing to follow-up and transplant to follow-up was noted in all groups among those patients who were alive at follow-up (Table S4, SDC, http://links.lww.com/TP/C94). Among patients who had at least 90 days of follow-up recorded, median functional status at follow-up was ≥90 in all groups (Table S5, SDC, http://links.lww.com/TP/C94).
Survival Analysis
One-year survival following OHT was significantly different based on bridging modality (P < 0.001) (Figure S1, SDC, http://links.lww.com/TP/C94). At 1 year, overall survival was 92.01% for no bridging, 92.84% for inotropes only, 91.55% for IABP, 89.71% for temporary VAD, 90.91% for durable VAD, and 80.51% for ECMO.
DISCUSSION
For eligible patients with end-stage heart failure, OHT offers the possibility of long-term survival. Nevertheless, the limited availability of donor organs necessitates selective allocation of donor hearts, which underscores the need for improved understanding of post-OHT outcomes including survival as well as functional status metrics. Recent changes in organ allocation have shifted the landscape of bridging modalities before OHT with an increased proportion of patients receiving ECMO, IABP, and temporary VAD support. Therefore, waitlisted candidates for OHT are more frequently critically ill requiring intensive care; however, the impact of this status on postoperative functional capability has yet to be fully explored. Herein, we found significant differences in baseline functional status at the time of listing and at the time of transplant in patients who were bridged to OHT, which was related to the bridging modality. This was an expected finding as sicker patients requiring higher risk temporary bridging modalities will likely have limited ambulatory and functional capacity. Overall, functional status increased significantly following transplant with a majority of patients being considered functionally independent at the time of follow-up. Importantly, among patients who are critically ill at the time of transplant and survive, acceptable functional outcomes can be achieved. Thus, the use of temporary MCS, which has increased with the recent UNOS allocation policy change, can allow for comparable functional outcomes compared with patients requiring no bridging, inotropes only, or durable VADs, in those patients who survive. It is important to place these findings in the context of overall reduced posttransplant survival, however, with the higher risk bridging modalities. As such, the data are not meant to imply equivalent outcomes between these patient cohorts but rather to suggest that specifically in survivors, that reasonable functional outcomes can be achieved even in those critically ill patients undergoing OHT.
In addition to survival rates, health-related quality of life has become an important focus to gauge the effectiveness of heart failure treatment and guide selection for OHT. This is perhaps best reflected in a 2013 American Heart Association scientific statement encouraging the assessment of patient-reported health status, which includes functional status.10 Prior work has also explored the relationship between frailty and OHT outcomes. Sepehri et al conducted a systematic review of the association between frailty and outcomes in patients undergoing any cardiac surgery and found that objective measures of frailty were correlated not only with mortality but also with rates of major adverse cardiac and cerebrovascular events following surgery as well as declines in functional status.11 Additionally, patients classified as being frail have been found to have higher rates of stroke and renal failure as well and prolonged length of stay following OHT.12 Thus, preoperative function is a critical factor to take into account to guide optimal management of patients with end-stage heart failure. Though we found wide variations in functional status, OHT was associated with significant improvements, suggesting that even those patients who are in a moribund state at the time of transplant stand to gain significant benefit. The decision to ultimately list and transplant an OHT candidate is multifactorial and should be placed in the context of posttransplant mortality risk as well. High-risk temporary bridging modalities such as ECMO have been shown to correlate with higher mortality risk following OHT.2 Nonetheless, the data from our study are somewhat encouraging in showing that those critically ill patients who survive post-OHT can enjoy acceptable functional status, with only a small minority requiring substantial assistance for activities of daily living. Nevertheless, functional status is only 1 component of quality of life, and further prospective studies will be necessary to fully understand how OHT can impact these metrics.
Prior studies have explored functional status in patients with advanced heart failure.13–15 In particular, among patients supported with an LVAD at 1-year following implantation, mean 6-minute walk distance approached that for patients without cardiovascular disease.16 Rogers et al found that approximately 80% of patients had New York Heart Association class I or II symptoms following LVAD implantation as compared with the majority having class IV symptoms preoperatively.17 Thus, MCS appears to improve quality of life for many patients. Similarly, return to work, as a marker of improved overall health status, has been explored following OHT. In one study, 60% of OHT recipients worked in the year before OHT and 50% worked at 1-year posttransplant.18 In contrast, Jalowiec et al reported that only 26% of recipients were working 1-year post-OHT.13 Nevertheless, patients undergoing OHT also display improved health-related quality of life and exercise capacity.14 These outcomes, however, are highly dependent upon the need for readmissions and any transplant-related complications. Additionally, patients should be counseled that it may take months to years to see these improvements, and thus a commitment to active rehabilitation following OHT may be an important factor in ensuring appropriate candidacy.19
At present, there is little data to guide selection of bridge-to-transplant approaches in patients with end-stage heart failure. Improved understanding of changes in functional status may represent an important metric in guiding selection and setting patient expectations. We found that the placement of a durable VAD was the only modality that resulted in an improvement in functional status between the time of listing and time of transplant. This is supported by work by others displaying improvements in functional status with the use of durable LVADs.1,14,16,17 In patients who may not be a candidate for OHT, for example, due to active smoking, the implantation of a durable LVAD is a well-established and effective strategy for supporting cardiac function until they become eligible. Our data shows that it may also be a reasonable strategy to improve functional capacity in patients who may be more debilitated from their heart failure and unlikely to tolerate OHT.
Organ allocation policies add further complexity to bridging selection, which is reflected in trends in the utilization of bridging modalities.4,5 As expected, we found that patients requiring IABP, ECMO, and temporary VADs demonstrated a lower baseline functional status but also displayed some of the highest improvements in Karnofsky status. In particular, the use of ECMO, which has increased from 1.1% to 4.9% of OHT patients following the UNOS allocation policy change, has previously been shown to be associated with a worse post-OHT functional status compared with patients bridged with a durable VAD.2,4 Poptsov et al, in a study of patients bridged to OHT with peripheral ECMO, reported that 86.1% of their patients were discharged to home.20 A study of patients in Europe bridged with VA-ECMO, with a comparable recipient age but significantly older donors (42 versus 33 y), reported an in-hospital survival rate of 66.7% with 54.4% surviving until discharge home.3 Thus, among these critically ill patients, who are prioritized as status 1 under the new allocation policy, favorable functional outcomes can still be achieved.21 Though follow-up functional status is not recorded at standardized intervals within the UNOS database, we found that, among patients with at least 90 days of follow-up, median functional status for patients bridged with temporary MCS fell within levels of normal activity. This suggests that critical illness requiring such support does not necessarily portend inferior functional outcomes in survivors.
Improved understanding of functional status also demonstrates opportunities for targeted improvements to improve overall outcomes for OHT patients. Appreciation of baseline functional status and trends in activity level before and after OHT may also help to guide interventions to increase quality of life in these patients.22 Assessment of functional status also exposes opportunities for engagement of multidisciplinary teams including physical and occupational therapy, dieticians, and social workers. Multiple studies have explored the role for formalized cardiac rehabilitation in patients undergoing OHT with conflicting results.23,24 After controlling for baseline 6-minute walk test, Rosenbaum et al found that participation in cardiac rehabilitation was positively associated with survival following OHT.25 Cardiac rehabilitation has also been associated with lower rates of major adverse cardiac events after OHT.26 Furthermore, functional status also reflects recipient dependence for help with activities of daily living. Delgado et al described relatively low caregiver burden following OHT, although this was influenced by rates of transplant-related complications.27 Engagement of other healthcare providers and the patient’s social support system may help to identify and address potential contributors to recipient functional status.
This study has several limitations. We utilized a multicenter database and thus data entry errors, missing data, inter-rater variability, and variability in follow-up could have influenced the study results. Measures of functional status were restricted to the Karnofsky performance scale, although undoubtedly there are other approaches to quantify functional status. We were unable to fully account for the effect of the October 2018 UNOS policy change given the significantly shorter follow-up time among the patients who underwent OHT under the new allocation guidelines. Long-term data will be necessary to compare functional outcomes as a result of the policy change. Finally, given the study design, we were unable to account for decision-making for bridging approach. The heterogeneity in baseline characteristics between the groups suggests that candidate symptoms and function may have influenced the decision to use no support, inotropic support, or temporary or durable mechanical support.
In conclusion, we report functional outcomes based on bridging modality among patients undergoing OHT. Differences in preoperative functional status reflect the varying clinical conditions of patients awaiting OHT, yet all groups of bridging modalities demonstrate significant improvement in function compared with baseline status. Importantly, despite the poor clinical condition of many patients who are bridged with temporary MCS, exploration of functional status at most recent follow-up reveals that many patients are able to achieve independent functioning despite moribund status at the time of transplant. Thus, with the shift in bridging modality accompanying the new UNOS allocation policy change, it is clear that acceptable outcomes can be accomplished for these acutely ill heart failure patients who will otherwise die without transplantation.
Supplementary Material
Acknowledgments
The authors declare no funding.
Footnotes
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