Usefulness of extracorporeal membrane oxygenation for early cardiac allograft dysfunction

doi:10.1016/j.healun.2011.01.728

The Journal of Heart and Lung Transplantation

Volume 30, Issue 7, July 2011, Pages 783-789

https://doi.org/10.1016/j.healun.2011.01.728 Get rights and content

Background

Owing to persisting donor shortages, the use of “marginal hearts” has increased. Because patients who receive a marginal heart may require hemodynamic support in the early post-operative period, extracorporeal membrane oxygenation (ECMO) may be used until recovery of acute graft dysfunction.

Methods

A retrospective file review of 124 primary adult heart transplant patients from 2003 to 2008 was conducted. We compared 17 patients who received post-transplant ECMO support with 107 transplant recipients without ECMO. Donor and recipient pre-transplant, intra-operative, and post-transplant clinical variables to 6 months after transplant were compared.

Results

Pre-operative demographics of the 2 groups were similar. Eight (47%) of the patients in the ECMO group received marginal donor hearts, compared with 1 (1%) in the non-ECMO group (p < 0.05). There were 3 early deaths in the ECMO group (2 of whom had received optimal donor hearts), resulting in lower Day 30 ECMO survival of 82.4% vs 100% for non-ECMO, respectively (p < 0.001), and 6-month survival of 82.4% vs 95.6%, respectively (p < 0.02). Most of the difference in survival was in patients who required salvage ECMO despite normal pre-transplant donor LV function. The rate of early dialysis was higher in the ECMO group, at 18% vs 6% at Day 3, but there was no difference between the 2 groups by Day 7. Pre-discharge ventricular function was normal in all discharged ECMO patients and all but 1 non-ECMO patient. ECMO patients had a longer intensive care unit stay (8.9 ± 3.4 vs 4.8 ± 5.4 days, p < 0.005), but there was a slightly shorter ward stay, resulting in a similar overall hospitalization length of stay (22.9 ± 8.3 vs 25.1 ± 25.2 days).

Conclusions

ECMO allows for salvage of acute graft dysfunction and may allow use of marginal donor hearts. Survival rates are lower in patients who require ECMO compared with optimal donors, but early cardiac dysfunction normalizes in most without long-term cardiac or renal sequelae. Despite longer ventilation times, overall hospitalization is not prolonged.

Section snippets

Methods

We reviewed consecutive heart transplantation outcomes in St. Vincent's Hospital, Sydney, Australia, from January 2003 to December 2008. This timeframe allowed comparison of outcomes in the ECMO era (2006–2008) with contemporaneous heart transplantation management (2003–2005) before the introduction of venoarterial ECMO into routine clinical use for the management of immediate graft dysfunction after transplant. Comparisons were made of the total data collected during the 6-year period

Patient demographics

Of the 124 patient records that were reviewed, 17 were supported with ECMO, with 1 ECMO patient in 2005, and 16 in 2006 to 2008. There was no significant change in basic patient demographics during the 2 periods. Pre-transplant etiology and mechanical support are reported in Table 1. All patients were managed with standard triple immunosuppression therapy (cyclosporin, mycophenolate, prednisolone) with anti-thymocyte globulin (ATG) induction therapy in 38%, which was similar between groups.

Donor demographics

Discussion

By providing short-term hemodynamic and oxygenation support, ECMO allows the successful use of marginal cardiac donors with impaired pre-transplant systolic function and successful transition after cardiotomy in patients with early non-specific graft dysfunction. Although survival rates are lower than in optimal donor hearts, ECMO resulted in an additional 8 heart transplantations with marginal donor hearts in our institution (13.3% of heart transplants for 2006–2008), and 7 of those patients

Disclosure statement

Dave R. Listijono and Alasdair Watson contributed equally as first authors.

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

The authors are grateful to Ross Petterson, who assisted with data retrieval.

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Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). Donor risk factors for the development of PGD are incompletely characterized. Donor management goals (DMG) are predefined critical care endpoints used to optimize donors. We evaluated the relationship between DMGs as well as non-DMG parameters, and the development of PGD after HT.
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Mild/moderate and severe PGD occurred in 15% and 6% of the cohort. Multivariable modeling revealed 6 variables independently associated with mild/moderate and 6 associated with severe PGD, respectively. Recipient use of amiodarone plus beta-blocker, recipient mechanical circulatory support, donor age, donor fraction of inspired oxygen (FiO₂), and donor creatinine increased risk whereas predicted heart mass ratio decreased risk of severe PGD. We found that donor age and FiO₂ ≥ 40% were associated with an increased risk of death within 90 days post-transplant in a multicenter cohort.
Donor hyperoxia at heart recovery is a novel risk factor for severe primary graft dysfunction and early recipient death. These results suggest that excessive oxygen supplementation should be minimized during donor management.
Extracorporeal Membrane Oxygenation for Graft Dysfunction Early After Heart Transplantation: A Systematic Review and Meta-analysis
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Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO.
We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%–39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%–57%). Recipient age (odds ratio 1.02, 95% CI 1.01–1.04) and prior sternotomy (OR 1.57, 95% CI 0.99–2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death.
One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT.
Improvements in Extracorporeal Membrane Oxygenation for Primary Graft Failure After Heart Transplant
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Citation Excerpt :
These changes procured positive results with survival to device weaning increased from 61% to 100% and a lower hazard of mortality compared with the previous approach. Compared with previous literature reporting 50% to 85% survival to discharge for PGF,3-11 our post-2017 survival to discharge of 76% was reasonable and a 37% increase from pre-2017. As survival to discharge for heart transplantation overall was 96% after 2017, PGF clearly portends worse survival in the initial hospital stay.
Severe primary graft failure is a life-threatening complication of heart transplantation that may require venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Surgical practices and management strategies regarding VA-ECMO vary between and within centers.
We performed a single-center retrospective cohort study on adult patients who received VA-ECMO for primary graft failure between 2013 and 2020. Clinical data were obtained from chart review and national databases. Patients were stratified by transplantation before or after 2017, when our center adopted additional objective criteria for VA-ECMO, adopted partial-flow support, and changed from central cannulation to chimney graft arterial cannulation of brachiocephalic, axillary, or aorta. The primary outcome was survival to device weaning. Secondary outcomes were survival to discharge, survival to 1 year, complications on support, and time to sedation weaning and extubation.
From 276 heart transplant recipients, 39 severe primary graft failure patients requiring VA-ECMO were identified. Incidence of graft failure was 13% (n = 18 of 135) pre-2017 and 15% (n = 21 of 141) post-2017. Survival at all time points improved significantly after 2017, with greatest difference in survival to device weaning (61% pre-2017 vs 100% post-2017). After controlling for other factors in multivariable Cox regression modeling, transplantation after 2017 was a predictor of reduced mortality (hazard ratio, 0.209; 95% CI, 0.06-0.71; P = .01). Significant differences were not observed in other secondary outcomes of recovery.
The new VA-ECMO strategy displayed reasonable survival and a remarkable improvement from the prior system.
Review of Postoperative Care for Heart Transplant Recipients
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The early postoperative management strategies after heart transplantation include optimizing the function of the denervated heart, correcting the causes of hemodynamic instability, and initiating and maintaining immunosuppressive therapy, allograft rejection surveillance, and prophylaxis against infections caused by immunosuppression. The course of postoperative support is influenced by the quality of allograft myocardial protection prior to implantation and reperfusion, donor-recipient heart size matching, surgical technique of orthotopic heart transplantation, and patient factors (eg, preoperative condition, immunologic compatibility, postoperative vasomotor tone, severity and reversibility of pulmonary vascular hypertension, pulmonary function, mediastinal blood loss, and end-organ perfusion). This review provides an overview of the early postoperative care of recipients and includes a brief description of the surgical techniques for orthotopic heart transplantation.
Analysis of the 2020 EACTS/ELSO/STS/AATS Expert Guidelines on the Management of Adult Postcardiotomy Extracorporeal Life Support
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Extracorporeal life support (ECLS), also known as extracorporeal membrane oxygenation (ECMO), increasingly is used in postcardiotomy (PC) shock to facilitate a bridge to sustained recovery, long-term mechanical support, or heart transplantation. Given increasing prevalence and complexity of PC-ECLS, a joint expert consensus guideline was created in 2020 for management of adult PC-ECLS by the European Association for Cardio-Thoracic Surgery (EACTS), the Extracorporeal Life Support Organization (ELSO), the Society of Thoracic Surgeons (STS), and the American Association of Thoracic Surgery (AATS). The aim of this analysis was to comprehensively review the expert consensus guidelines, with particular emphasis on PC-ECLS candidacy, timing, cannula configuration, left ventricular distention, anticoagulation, ECLS weaning, and intensive care unit complications. This analysis finds the expert consensus guideline to be timely, pertinent, and clinically valuable, although there remains the need for larger clinical trials to codify best practices.
Donor Left Ventricular Function Assessed by Echocardiographic Strain is a Novel Predictor of Primary Graft Failure After Orthotopic Heart Transplantation
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This study sought to determine the utility of donor left ventricular function assessment by echocardiographic left ventricular global longitudinal strain (LV GLS) in predicting primary graft failure (PGF) after orthotopic heart transplantation (HT).
Retrospective, observational study.
Tertiary referral hospital.
Adult patients (>18 years) who underwent isolated HT.
Demographic, clinical, and echocardiographic data were collected on 100 patients who underwent HT between January 2010 and December 2019 at the authors’ institution. The respective donor variables, as well as procedural factors, were reviewed and analyzed to assess their independent association with PGF. Standard donor echocardiographic measurements were supplemented by two-dimensional speckle-tracking echocardiography to obtain LV GLS. PGF was defined as per the International Society for Heart and Lung Transplantation 2014 consensus statement.
PGF occurred in 40 of the 100 patients (40%). Initial univariate analysis found that RADIAL score, donor ejection fraction, and donor LV GLS were associated with PGF. However, in a multivariate Cox regression analysis, only RADIAL score and donor LV GLS remained significant predictors of PGF, with a p < 0.001. By receiver operating characteristic curve analysis, LV GLS at a cut-off value of –11.5% showed the greatest area under the curve (area under the curve = 0.889; 95% confidence interval, 0.826-0.952) and predicted PGF with 92.5% sensitivity and 65% specificity.
Impaired donor LV GLS was proven to be an independent predictor of PGF after HT.

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Original clinical scienceUsefulness of extracorporeal membrane oxygenation for early cardiac allograft dysfunction

Background

Methods

Results

Conclusions

Section snippets

Methods

Patient demographics

Donor demographics

Discussion

Disclosure statement

J Cardiothorac Anesth

Ann Thorac Surg

J Heart Lung Transplant

Ann Thorac Surg

Ann Thorac Surg

Transplant Proc

Transplant Proc

Ann Thorac Surg

J Am Coll Cardiol

J Heart Lung Transplant

Transplant Proc

Original clinical science
Usefulness of extracorporeal membrane oxygenation for early cardiac allograft dysfunction