Abstract
Background
Post‐operative stroke increases morbidity and mortality after cardiac surgery. Data on characteristics and outcomes of stroke after heart transplantation (HTx) are limited.
Methods and results
We conducted a retrospective analysis of the United Network for Organ Sharing (UNOS) database from 2009 to 2020 to identify adults who developed stroke after orthotropic HTx. Heart transplant recipients were divided according to the presence or absence of post‐operative stroke. The primary endpoint was all‐cause mortality. A total of 25 015 HT recipients were analysed, including 719 (2.9%) patients who suffered a post‐operative stroke. The stroke rates increased from 2.1% in 2009 to 3.7% in 2019, and the risk of stroke was higher after the implantation of the new allocation system [odds ratio 1.29, 95% confidence intervals (CI) 1.06–1.56, P = 0.01]. HTx recipients with post‐operative stroke were older (P = 0.008), with higher rates of prior cerebrovascular accident (CVA) (P = 0.004), prior cardiac surgery (P < 0.001), longer waitlist time (P = 0.04), higher rates of extracorporeal membrane oxygenation (ECMO) support (P < 0.001), left ventricular assist devices (LVADs) (P < 0.001), mechanical ventilation (P = 0.003), and longer ischaemic time (P < 0.001). After multivariable adjustment for recipient and donor characteristics, age, prior cardiac surgery, CVA, support with LVAD, ECMO, ischaemic time, and mechanical ventilation at the time of HTx were independent predictors of post‐operative stroke. Stroke was associated with increased risk of 30 day and all‐cause mortality (hazard ratio 1.49, 95% CI 1.12–1.99, P = 0.007).
Conclusions
Post‐operative stroke after HTx is infrequent but associated with higher mortality. Redo sternotomy, LVAD, and ECMO support at HTx are among the risk factors identified.
Keywords: Post‐operative stroke, Heart transplantation, Mortality
Introduction
Heart transplantation (HTx) continues to be standard of care for selected patients with advanced heart failure with a 1 year survival of approximately 90%. 1 , 2 Primary graft failure and infection are the most prevalent causes of death in the first 30 days and 1 year, respectively. 3 Advances in clinical management, organ selection and preservation, desensitization protocols, and changes in allocation policies continue to improve heart transplant recipients' survival and quality of life. 4
Patients undergoing HTx have a lower risk of stroke than patients with heart failure on the waiting list. 5 However, HTx has been associated with a higher risk of stroke than other cardiac surgery types, with stroke incidence between 5% and 11%. Approximately 20% will occur within 2 weeks after HTx. 6 , 7 , 8 Zierer et al. identified advanced age, preoperative left ventricular assist device (LVAD) support, preoperative intra‐aortic balloon pump (IABP), prolonged cardiopulmonary bypass, and post‐operative hepatic failure as independent predictors of early neurologic complications. 9 Early stroke after HTx has been associated with decreased long‐term survival in children. 10 A higher proportion of cryptogenic stroke and unusual stroke causes have been reported in HTx recipients. 11 A recent analysis of the Scientific Registry of Transplant Recipients database did not identify stroke as a significant factor related to early, constant, or late mortality risk. 12
In October 2018, a six‐tier heart transplant allocation system replaced the three‐tier system in the USA. 13 We would highlight two of those changes. First, the Status 1 of the old system was divided into three statuses: Status 1 [extracorporeal membrane oxygenation (ECMO), nondischargeable biventricular assist devices, and mechanical circulatory support (MCS) devices with ventricular tachycardia], Status 2 (IABP, percutaneous ventricular assist devices, surgical nondischargeable LVAD, total artificial heart, MCS with device failure and ventricular tachycardia, or fibrillation), and Status 3 (LVAD 30 days, high dose or >1 inotrope, Statuses 1 and 2 after 14 days, and MCS with other complications). Second, the organ distribution area was expanded to 500 nautical miles from the transplant centre for Status 1 and 2 patients. Studies analysing the impact of the new allocation system have reported a significant increase in preoperative MCS (e.g. IABP: 7.6% ➔ 26.2%; ECMO: 1.4% ➔ 5.1%), increased ischaemic time, and a decrease in waitlist mortality, and some reports increased post‐transplant mortality, but this has not been consistent. 14 , 15 , 16 , 17 , 18
The information about the incidence of post‐operative stroke in the current era and the potential impact of the new allocation system is scarce. 19 To address this knowledge gap, we performed an analysis of the United Network for Organ Sharing (UNOS) database to investigate the trends, risk factors, and prognostic implications of post‐operative stroke in heart transplant recipients.
Methods
Data source
We analysed the UNOS database from the thoracic organ transplant registry from 2009 to 2019, with follow‐up through January 2020. The data include all patients undergoing thoracic organ transplantation in the USA. The registry records additional clinical information at the time of transplant, such as perioperative events, and continues to follow the recipient after transplant.
Study design and patient population
All first‐time HTx recipients who were 18 years old or older were included. Patients who received a multiorgan transplant or in whom post‐operative stroke information was missing were excluded. Patients were primarily stratified by the presence or absence of post‐operative stroke as documented in the UNOS database.
Outcomes
Baseline characteristics and risk factors for post‐operative stroke were analysed. The primary outcome was all‐cause mortality.
Statistical analysis
We compared baseline characteristics between study groups using χ 2 test for categorical variables and the independent‐sample t‐test or Wilcoxon rank‐sum test (as appropriate) for continuous variables. Risk factors for post‐operative stroke identified in univariate analysis with P < 0.05 were included in the multivariable logistic regression model. Mortality was assessed for all risk factors, including post‐operative stroke, in a univariate model. Significant risk factors (donor and recipient characteristics) were then analysed with a multivariable analysis using the Cox proportional hazard regression model. Survival was analysed using the Kaplan–Meier method with statistical differences between survival curves assessed using the Mantel–Cox log‐rank test. In addition, modelling based on 30 day landmark analysis was performed to assess long‐term survival independent of early mortality. To evaluate the interaction the heart allocation policies, we assessed the incidence of stroke before and after October 2018 and the associated survival. Variables with more than 10% missing data were excluded from the multivariable model. All statistical tests were two‐sided, and P < 0.05 was considered to indicate statistical significance. Analyses were performed using Stata software, Version 16 (StataCorp LLC).
Results
We identified 28 385 adult patients (18 years or older) who underwent HTx during the study period. After excluding patients who had multiorgan transplantation (n = 2112) or whose stroke information was missing (n = 1258), a total of 25 015 patients were included in the study. Of the 25 015 patients, 719 patients (2.9%) had a post‐operative stroke. The prevalence of stroke ranged from 1.9% in 2010 to 3.76% in 2019. The trends in post‐operative stroke during the study period are shown in Figure 1 .
Figure 1.
Trends in post‐operative stroke incidence after heart transplantation.
Heart transplantation recipients with post‐operative stroke were older (P = 0.008), with higher rates of prior cerebrovascular accident (CVA) (P = 0.004), prior cardiac surgery (P < 0.001), longer waitlist time (P = 0.04), higher rates of ECMO support (P < 0.001), LVADs (P < 0.001), mechanical ventilation (P = 0.003), and longer ischaemic time (P < 0.001) (Table 1 ). After multivariable adjustment for recipient and donor characteristics listed in Table 1 , age, prior cardiac surgery, CVA, support with LVAD, ECMO, ischaemic time, and mechanical ventilation at the time of HTx were independent predictors of post‐operative stroke (Figure 2 ).
Table 1.
Baseline characteristics among patients with and without stroke after heart transplantation
| Variable | Without post‐operative stroke (n = 24 296) | With post‐operative stroke (n = 719) | P‐value |
|---|---|---|---|
| Recipient characteristics | |||
| Age at transplantation, years (SD) | 53 (13) | 54 (12) | 0.008 |
| Ethnicity | |||
| White (%) | 15 947 (66) | 490 (68) | 0.364 |
| Black (%) | 5238 (22) | 136 (19) | |
| Other (%) | 3111 (13) | 103 (14) | |
| BMI at listing, kg/m2 (SD) | 27 (5) | 27 (5) | 0.869 |
| Female gender (%) | 6401 (26) | 189 (26) | 0.972 |
| ABO blood group | |||
| 0 (%) | 9495 (39) | 283 (39) | 0.284 |
| A (%) | 9764 (40) | 309 (43) | |
| B (%) | 3648 (15) | 100 (14) | |
| AB (%) | 1389 (57) | 27 (4) | |
| Diabetes (%) | 6773 (28) | 208 (29) | 0.682 |
| Smoking (%) | 11 235 (46) | 333 (46) | 0.962 |
| Prior CVA (%) | 1441 (6) | 61 (9) | 0.004 |
| Ischaemic time, h (SD) | 3.18 (1.05) | 3.36 (1.18) | <0.001 |
| Prior cardiac surgery (%) | 9594 (40) | 365 (52) | <0.001 |
| Creatinine, mg/dL (SD) | 1.2 (0.5) | 1.2 (0.5) | 0.153 |
| Albumin, mg/dL (SD) | 3.7 (0.7) | 3.7 (0.7) | 0.215 |
| Implantable defibrillator (%) | 18 922 (79) | 521 (74) | 0.002 |
| Days on Status 1a (SD) | 30 (58) | 33 (61) | 0.129 |
| Total days on waitlist (SD) | 225 (367) | 253 (423) | 0.044 |
| Inotropes at transplant (%) | 9008 (37) | 201 (28) | <0.001 |
| IABP at transplant (%) | 2499 (10) | 67 (9) | 0.4 |
| VAD type at transplant (%) | |||
| None (%) | 13 443 (55) | 275 (38) | <0.001 |
| LVAD (%) | 10 067 (41) | 395 (55) | |
| RVAD (%) | 46 (0.2) | 3 (0.4) | |
| TAH (%) | 241 (0.9) | 19 (3) | |
| LVAD + RVAD (%) | 498 (2) | 27 (4) | |
| ECMO at transplant (%) | 314 (1) | 29 (4) | <0.001 |
| Mechanical ventilation at transplant (%) | 315 (1) | 27 (4) | <0.001 |
| Acute rejection (%) | 2121 (9) | 55 (8) | 0.448 |
| Post‐transplant dialysis (%) | 2572 (11) | 262 (37) | <0.001 |
| Post‐transplant pacemaker (%) | 701 (3) | 30 (4) | 0.04 |
| Need for blood transfusion (%) | 5238 (22) | 217 (31) | <0.001 |
| Donor characteristics | |||
| Donor age (SD) | 32 (11) | 33 (12) | 0.112 |
| Donor ethnicity | |||
| White (%) | 15 618 (64) | 455 (63) | 0.904 |
| Black (%) | 3952 (16) | 120 (17) | |
| Other (%) | 4726 (19) | 144 (20) | |
| Donor ABO | |||
| O (%) | 12 243 (50) | 365 (51) | 0.198 |
| A (%) | 8770 (36) | 266 (37) | |
| B (%) | 2718 (11) | 80 (11) | |
| AB (%) | 565 (2) | 8 (1) | |
| Donor female gender (%) | 7186 (30) | 195 (27) | 0.155 |
| Donor BUN, mg/dL (SD) | 22 (18) | 22 (17) | 0.857 |
| Donor creatinine, mg/dL (SD) | 1.5 (1.5) | 1.5 (1.4) | 0.887 |
| Donor SGOT, mg/dL (SD) | 105 (317) | 113 (374) | 0.493 |
| Donor SGPT, mg/dL (SD) | 114 (436) | 105 (241) | 0.569 |
| Donor total bilirubin, mg/dL (SD) | 1.1 (1.4) | 1.1 (1.7) | 0.353 |
| Donor diabetes (%) | 6773 (28) | 208 (29) | 0.682 |
| Donor BMI, kg/m2 | 28 (6) | 28 (7) | 0.047 |
BMI, body mass index; ECMO, extracorporeal membrane oxygenation; LVAD, left ventricular assist device; RVAD, right ventricular support device; SD, standard deviation; SGOT, serum glutamic oxaloacetic transaminase; SGPT, serum glutamic‐pyruvic transaminase; TAH, total artificial heart. P‐values in bold are statistically significant.
Figure 2.
Forest plot depicting the risk factor for post‐operative stroke after multivariable adjustment for donor and recipient characteristics. ECMO, extracorporeal membrane oxygenation; ICD, implantable cardioverter defibrillator; LVAD, left ventricular assist device.
Patients with stroke had higher rates of haemodialysis after HTx (37% vs. 11% among those without stroke, P < 0.001) and blood transfusion (31% vs. 22% among those without stroke, P < 0.001). Three hundred forty‐two patients with stroke died (47.6%) compared with 4657 patients without stroke (19.2%). Among those with stroke, 148 patients died within the first 30 days after HTx (43.3% of deaths vs. 15.2% among those without stroke). Stroke was associated with increased risk of 30 day [odds ratio 4.44, 95% confidence intervals (CI) 3.52–5.60, P < 0.001] and all‐cause mortality after HT after multivariable adjustment [hazard ratio (ΗR) 1.49, 95% CI 1.12–1.99, P = 0.007] (Figure 3A and 3B ). Overall, the 30 day landmark survival was significantly lower in patients with stroke after adjustment for the recipient and donor characteristics (HR 1.4, 95% CI 1.1–1.9, P = 0.017).
Figure 3.
Kaplan–Meier curves of (A) overall survival and (B) adjusted overall survival after heart transplantation.
A total of 3598 patients analysed in the new allocation system of those 127 had a post‐operative stroke. Notably, the ischaemic time was significantly higher in the new allocation system (new 3.43 ± 1.03 h vs. old 3.15 ± 1.05, P < 0.0001). The risk of stroke was higher after implementing the new allocation system (odds ratio 1.29, 95% CI 1.06–1.56, P = 0.01).
Discussion
The salient findings of this retrospective analysis of heart transplant recipients with and without post‐operative stroke from a nationwide representative database from 2009 to 2020 can be summarized as follows: (i) the incidence of post‐operative stroke is 2.9% after HTx; (ii) the incidence of stroke has increased during the study period; (iii) prior cardiac surgery, longer ischaemic time, LVAD, and ECMO support at HTx are risk factors for stroke; (iv) HTx recipients with stroke had higher rates of mechanical ventilation and need for dialysis and blood transfusion; (v) post‐operative stroke is an independent predictor of all‐cause mortality after HTx; and (vi) the risk of stroke was higher after implementation of the new allocation system.
Stroke and encephalopathy are the most frequent neurologic complications after cardiac surgery. The incidence of stroke depends on the complexity and number of cardiac procedures performed and has declined after coronary artery bypass graft surgery despite an increasing patient risk profile. 20 Most strokes occur post‐operatively in the first 2 days after cardiac surgery, while at least one‐third of strokes occur intraoperatively, 20 with an increased risk of stroke persisting up to 2 years after surgery. 21 However, it is important to note that in analyses of large databases, only clinical stroke is reported as the incidence of ‘silent’ stroke uncovered by neuroimaging is estimated to be much higher. 22 Similarly, in our study, the stroke incidence is comparable with that reported among patients who underwent combined valvular and coronary artery bypass graft surgery. 23 Still, it is possible that due to lack of neuroimaging data, the rates of subclinical stroke are much higher.
Regarding risk factors related to post‐operative stroke, advanced age, prior stroke, atherosclerosis of the ascending aorta, carotid arteries, renal failure, diabetes, left ventricular dysfunction, and operative parameters related to the complexity of the surgery and cardiopulmonary bypass are commonly identified in large cohort analyses. 20 , 21 , 22 , 23 In our study, patients with post‐operative stroke tended to be overall ‘sicker’ with higher rates of prior cardiac surgery, need for ECMO support, and use of LVAD at the time of HT. Furthermore, patients with stroke developed additional complications such as need for dialysis and bleeding requiring blood transfusions more frequently than those without stroke. Although this large registry data do not elucidate mechanisms responsible for post‐operative stroke, various causes such as cerebral hypoperfusion from intraoperative hypotension or diminished cardiac output, athero‐, thrombo‐, or air‐embolization due to manipulation of the aorta and cardioembolic due to atrial fibrillation are responsible for these events. Patients with LVAD usually have longer operative and cardiopulmonary bypass time due to the operative complexity related to prior sternotomy and device explantation. These unique operative challenges may increase the risk of stroke due to intraoperative hypotension and embolization and translate into higher rates of complications after HTx. 24 Also, the increasing utilization of LVADs as a bridge to transplantation in the past decade may explain the increasing trend in post‐operative stroke after HT. In our analysis, HTx recipients with stroke had longer ischaemic time, which further increased in this population after implementing the new allocation system and may explain the higher rates of stroke. With regard to atrial fibrillation, the frequency of this early after surgery is lower compared with its incidence post‐pericardiectomy in the setting of other cardiac surgeries, and this is likely due to surgical pulmonary vein isolation and cardiac denervation that occur with HT in addition to the frequent use of amiodarone among the heart failure population before HTx. 25 Lastly, the higher risk of stroke seen in the era after the implementation of the new allocation in October 2018 is concerning. Among the risk factors for post‐operative stroke, ECMO and ischaemic time are increasing since the implementation of the new allocation system. 14 , 15 , 26 Stroke affects approximately 4% of patients with venoarterial ECMO, and the cause is multifactorial. 27 Careful monitoring of neurological status, anticoagulation management, and left ventricular venting strategies may mitigate complications. 28 Alternative percutaneous transvalvular or surgical biventricular MCS can be considered. 29 , 30 The use of ex vivo perfusion technologies may modulate the risk associated with prolonged ischaemic time such as stroke. 31 The FDA approved an Organ Care System for clinical use, and post‐approval monitoring would help to evaluate the impact of ex vivo perfusion in post‐operative stroke. 32 More data need to be accumulated before safe conclusions about the characteristics of HTx recipients and their impact on post‐operative complications and mortality in the current allocation system can be reached.
The interpretation of the findings presented here should be performed in light of specific limitations inherent to the source of data and study design. First, this was a retrospective analysis of the UNOS database, and analysis is constrained to available information in the dataset. Information about the timing, type, radiographic, and clinical severity of these events is lacking. Therefore, we cannot determine post‐operative stroke's impact on the quality of life, functional status, recurrent stroke risk, and overall mortality. Second, the observational nature of the analysis implies that the effect of the changes in allocation policy reported represents an association only, and a causal effect cannot be determined. Although we adjusted for multiple confounding factors, the possibility of residual confounding cannot be eliminated. Third, only limited data are available after the most recent policy change in 2018; hence, this policy change's long‐term impact is yet to be determined. Our study's main strength is that UNOS is a clinical database currently used broadly for epidemiologic analysis and outcomes with data reflecting current practices in the USA.
In conclusion, post‐operative stroke after HTx is uncommon, but it is accompanied by a considerable impact on mortality. Its incidence has increased and occurs with other serious complications, particularly in patients requiring MCS with LVADs or ECMO. Given the overall improving outcomes after HTx, it is crucial to focus on early identification and prevention of often disabling complications such as stroke. Approaches to decrease ischaemic time, especially after implementing the new allocation system, may reduce stroke rates. Future studies should investigate the mechanisms, timing, and imaging characteristics of post‐operative stroke and examine its effects on long‐term cognitive function, functional status, and heart transplant patients' quality of life.
Conflict of interest
No conflict of interest declared.
Alvarez, P. , Kitai, T. , Okamoto, T. , Niikawa, H. , McCurry, K. R. , Papamichail, A. , Doulamis, I. , and Briasoulis, A. (2021) Trends, risk factors, and outcomes of post‐operative stroke after heart transplantation: an analysis of the UNOS database. ESC Heart Failure, 8: 4211–4217. 10.1002/ehf2.13562.
References
- 1. Kittleson MM. Recent advances in heart transplantation. F1000Res 2018; 7: F1000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL, American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines . 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013; 128: e240–e327. [DOI] [PubMed] [Google Scholar]
- 3. Lund LH, Khush KK, Cherikh WS, Goldfarb S, Kucheryavaya AY, Levvey BJ, Meiser B, Rossano JW, Chambers DC, Yusen RD, Stehlik J, International Society for Heart and Lung Transplantation . The registry of the International Society for Heart and Lung Transplantation: thirty‐fourth adult heart transplantation Report‐2017; focus theme: allograft ischemic time. J Heart Lung Transplant 2017; 36: 1037–1046. [DOI] [PubMed] [Google Scholar]
- 4. Kittleson MM, Kobashigawa JA. Cardiac transplantation: current outcomes and contemporary controversies. JACC Heart Fail 2017; 5: 857–868. [DOI] [PubMed] [Google Scholar]
- 5. Merkler AE, Chen ML, Parikh NS, Murthy SB, Yaghi S, Goyal P, Okin PM, Karas MG, Navi BB, Iadecola C, Kamel H. Association between heart transplantation and subsequent risk of stroke among patients with heart failure. Stroke 2019; 50: 583–587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Gaudino M, Angiolillo DJ, di Franco A, Capodanno D, Bakaeen F, Farkouh ME, Fremes SE, Holmes D, Girardi LN, Nakamura S, Head SJ, Park SJ, Mack M, Serruys PW, Ruel M, Stone GW, Tam DY, Vallely M, Taggart DP. Stroke after coronary artery bypass grafting and percutaneous coronary intervention: incidence, pathogenesis, and outcomes. J Am Heart Assoc 2019; 8: e013032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. van de Beek D, Kremers W, Daly RC, Edwards BS, Clavell AL, McGregor CG, Wijdicks EF. Effect of neurologic complications on outcome after heart transplant. Arch Neurol 2008; 65: 226–231. [DOI] [PubMed] [Google Scholar]
- 8. Belvís R, Martí‐Fàbregas J, Cocho D, García‐Bargo MD, Franquet E, Agudo R, Brosa V, Campreciós M, Puig M, Martí‐Vilalta JL. Cerebrovascular disease as a complication of cardiac transplantation. Cerebrovasc Dis 2005; 19: 267–271. [DOI] [PubMed] [Google Scholar]
- 9. Zierer A, Melby SJ, Voeller RK, Guthrie TJ, Al‐Dadah AS, Meyers BF, Pasque MK, Ewald GA, Moon MR, Moazami N. Significance of neurologic complications in the modern era of cardiac transplantation. Ann Thorac Surg 2007; 83: 1684–1690. [DOI] [PubMed] [Google Scholar]
- 10. Cammock C, Choudhry S, Castleberry CM, Al‐Hammadi N, Eghtesady P, Canter CE, Simpson KE. Early stroke post‐heart transplant is associated with decreased survival in children. J Heart Lung Transplant 2018; 37: 733–739. [DOI] [PubMed] [Google Scholar]
- 11. Acampa M, Lazzerini PE, Guideri F, Tassi R, Martini G. Ischemic stroke after heart transplantation. J Stroke 2016; 18: 157–168. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Hsich EM, Blackstone EH, Thuita LW, McNamara DM, Rogers JG, Yancy CW, Goldberg LR, Valapour M, Xu G, Ishwaran H. Heart transplantation: an in‐depth survival analysis. JACC Heart Fail 2020; 8: 557–568. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Estep JD, Soltesz E, Cogswell R. The new heart transplant allocation system: early observations and mechanical circulatory support considerations. J Thorac Cardiovasc Surg 2021; 161: 1839–1846. [DOI] [PubMed] [Google Scholar]
- 14. Kilic A, Mathier MA, Hickey GW, Sultan I, Morell VO, Mulukutla SR, Keebler ME. Evolving trends in adult heart transplant with the 2018 heart allocation policy change. JAMA Cardiol 2021; 6: 159–167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Ganapathi AM, Lampert BC, Mokadam NA, Emani S, Hasan AK, Tamer R, Whitson BA. Allocation changes in heart transplantation: what has really changed?J. Thorac Cardiovasc Surg 2021. [DOI] [PubMed] [Google Scholar]
- 16. Liu J, Yang BQ, Itoh A, Masood MF, Hartupee JC, Schilling JD. Impact of new UNOS allocation criteria on heart transplant practices and outcomes. Transplant Direct 2021; 7: e642. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Cogswell R, John R, Estep JD, Duval S, Tedford RJ, Pagani FD, Martin CM, Mehra MR. An early investigation of outcomes with the new 2018 donor heart allocation system in the United States. J Heart Lung Transplant 2020; 39: 1–4. [DOI] [PubMed] [Google Scholar]
- 18. Goff RR, Uccellini K, Lindblad K, Hall S, Davies R, Farr M, Silvestry S, Rogers JG. A change of heart: preliminary results of the US 2018 adult heart allocation revision. Am J Transplant 2020; 20: 2781–2790. [DOI] [PubMed] [Google Scholar]
- 19. Gunasekaran Prasad C, Bickel T, Parashara D. Use of mechanical circulatory support leading to heart transplant is associated with strokes in the immediate post‐transplant period: analysis of 59,170 heart transplants from the unos database. J Am Coll Cardiol 2016; 67: 1268–1268. [Google Scholar]
- 20. Tarakji KG, Sabik JF 3rd, Bhudia SK, Batizy LH, Blackstone EH. Temporal onset, risk factors, and outcomes associated with stroke after coronary artery bypass grafting. JAMA 2011; 305: 381–390. [DOI] [PubMed] [Google Scholar]
- 21. Whitlock R, Healey JS, Connolly SJ, Wang J, Danter MR, Tu JV, Novick R, Fremes S, Teoh K, Khera V, Yusuf S. Predictors of early and late stroke following cardiac surgery. CMAJ 2014; 186: 905–911. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Messé SR, Acker MA, Kasner SE, Fanning M, Giovannetti T, Ratcliffe SJ, Bilello M, Szeto WY, Bavaria JE, Hargrove WC 3rd, Mohler ER 3rd, Floyd TF, Determining Neurologic Outcomes from Valve Operations (DeNOVO) Investigators . Stroke after aortic valve surgery: results from a prospective cohort. Circulation 2014; 129: 2253–2261. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Shahian DM, O'Brien SM, Filardo G, Ferraris VA, Haan CK, Rich JB, Normand SL, DeLong ER, Shewan CM, Dokholyan RS, Peterson ED, Edwards FH, Anderson RP, Society of Thoracic Surgeons Quality Measurement Task Force . The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 3‐‐valve plus coronary artery bypass grafting surgery. Ann Thorac Surg 2009; 88: S43–S62. [DOI] [PubMed] [Google Scholar]
- 24. Asleh R, Alnsasra H, Daly RC, Schettle SD, Briasoulis A, Taher R, Dunlay SM, Stulak JM, Behfar A, Pereira NL, Frantz RP, Edwards BS, Clavell AL, Kushwaha SS. Predictors and clinical outcomes of vasoplegia in patients bridged to heart transplantation with continuous‐flow left ventricular assist devices. J Am Heart Assoc 2019; 8: e013108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Rivinius R, Helmschrott M, Ruhparwar A, Schmack B, Erbel C, Gleissner CA, Akhavanpoor M, Frankenstein L, Darche FF, Schweizer PA, Thomas D, Ehlermann P, Bruckner T, Katus HA, Doesch AO. Long‐term use of amiodarone before heart transplantation significantly reduces early post‐transplant atrial fibrillation and is not associated with increased mortality after heart transplantation. Drug Des Devel Ther 2016; 10: 677–686. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Parker WF, Chung K, Anderson AS, Siegler M, Huang ES, Churpek MM. Practice changes at U.S. transplant centers after the new adult heart allocation policy. J Am Coll Cardiol 2020; 75: 2906–2916. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Guglin M, Zucker MJ, Bazan VM, Bozkurt B, El Banayosy A, Estep JD, Gurley J, Nelson K, Malyala R, Panjrath GS, Zwischenberger JB, Pinney SP. Venoarterial ECMO for adults: JACC scientific expert panel. J Am Coll Cardiol 2019; 73: 698–716. [DOI] [PubMed] [Google Scholar]
- 28. Rao P, Khalpey Z, Smith R, Burkhoff D, Kociol RD. Venoarterial extracorporeal membrane oxygenation for cardiogenic shock and cardiac arrest. Circ Heart Fail 2018; 11: e004905. [DOI] [PubMed] [Google Scholar]
- 29. Takeda K, Garan AR, Ando M, Han J, Topkara VK, Kurlansky P, Yuzefpolskaya M, Farr MA, Colombo PC, Naka Y, Takayama H. Minimally invasive CentriMag ventricular assist device support integrated with extracorporeal membrane oxygenation in cardiogenic shock patients: a comparison with conventional CentriMag biventricular support configuration. Eur J Cardiothorac Surg 2017; 52: 1055–1061. [DOI] [PubMed] [Google Scholar]
- 30. Combes A, Price S, Slutsky AS, Brodie D. Temporary circulatory support for cardiogenic shock. The Lancet 2020; 396: 199–212. [DOI] [PubMed] [Google Scholar]
- 31. Ardehali A, Esmailian F, Deng M, Soltesz E, Hsich E, Naka Y, Mancini D, Camacho M, Zucker M, Leprince P, Padera R, Kobashigawa J, PROCEED II trial investigators . Ex‐vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open‐label, multicentre, randomised non‐inferiority trial. Lancet 2015; 385: 2577–2584. [DOI] [PubMed] [Google Scholar]
- 32. FDA . Questions for the Advisory Committee meeting for the TransMedics OCS Heart System for
- 33. expanded criteria donor hearts. [cited 2021 5/8/2021]; Available from: https://www.fda.gov/media/147287/download