What are the results of venoarterial extracorporeal membrane oxygenation bridging to heart transplantation?

Summary

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether heart transplantation is a viable treatment option in patients in refractory cardiogenic shock who could not be weaned off venoarterial extracorporeal membrane oxygenation (VA ECMO). Altogether, 373 papers were found using the reported search, of which 7 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Evidence is derived from 3 papers based on registry analysis, 1 multi-institutional study and 3 single-institution reviews. Early post-transplant mortality of ECMO-bridged recipients ranges from 18.7% to 33.3% and 1-year survival from 44.6% to 72.0%. High acuity of recipient illness reflected by poor renal function, mechanical ventilation, advanced age, elevated serum lactate predict inferior outcome. We conclude that heart transplantation results in patients bridged with VA ECMO are inferior when compared to published outcome of non-bridged recipients. In the era of severe organ shortage and intense public and regulatory scrutiny of the results, the decision to transplant a patient directly of VA ECMO needs to be made on a case-by-case basis. Potential gain in decreasing the waiting list mortality of these critically ill patients needs to be weighed against poorer post-transplantation mortality rates and mid- and long-term outcomes.

INTRODUCTION

A best evidence topic in cardiac surgery was written according to a structured protocol. This is fully described in the ICVTS [1].

THREE-PART QUESTION

In [patients with refractory cardiogenic shock supported by venoarterial extracorporeal membrane oxygenation] is [a heart transplantation] an acceptable [treatment option in the era of severe organ shortage]?

CLINICAL SCENARIO

The patient is a 44-year-old male with acute cardiogenic shock. He was emergently placed on peripheral venoarterial (VA) membrane oxygenation via percutaneous approach. Although end organ functions have normalized, all attempts to wean him from the extracorporeal support have been unsuccessful. The multidisciplinary team has determined that he is a good candidate for heart transplantation. On 18 October 2018, the Organ Procurement and Transplantation Network (OPTN) implemented a new 6-tiered heart allocation policy for the United States, giving the highest priority (Tier 1) status to patients meeting criteria for cardiogenic shock who are supported on extracorporeal membrane oxygenation (ECMO) [2]. In light of this change, we decided to perform a qualitative review of literature with data pertinent to heart transplantation results in patients bridged with VA ECMO.

SEARCH STRATEGY

A search was performed in MEDLINE from 1970 to August 2018 using PUBMED interface. The search strategy was as follows: ((((((((((((((extracorporeal membrane oxygenation[Title/Abstract] OR ECMO[Title/Abstract]))) OR extracorporeal life support[Title/Abstract]) OR LVAD[MeSH Terms] OR VAD[MeSH Terms]) AND (heart transplantation[Title/Abstract] OR heart transplant[Title/Abstract]))) NOT graft failure[Title/Abstract])) NOT children[Title/Abstract]))))).

SEARCH OUTCOME

Altogether 373 papers were found using the reported search of which 7 represented the best evidence to answer the clinical question. Evidence is derived from 3 papers based on registry analysis, 1 multi-institutional study and 3 single-institution reviews. The results of 2 studies from the United States, 4 from Europe and 1 from Asia are presented in Table 1. The total number of patients included in each study ranged from 15 to 157, with only 3 registry-based papers involving more than 50 patients. Various methods of analysis were utilized as described individually below.

RESULTS

The following studies examined the impact of pretransplant bridging with VA ECMO on post-transplant survival.

Zalawadiya et al. [3] scrutinized the post-heart transplantation outcome in 157 VA ECMO-supported patients reported to the United Network for Organ Sharing (UNOS) Registry between 1 January 2000 and September 2015. Survival at 1 year of 57.8% was mostly driven by high perioperative mortality. For patients surviving the first 30 days after transplant, long-term survival was acceptable (82.3% at 1 year and 76.2% at 5 years). Cox proportional hazard analysis revealed recipient glomerular filtration rate <45 ml/min/1.73 m² or dialysis [hazard ratio (HR) 2.27, 95% confidence interval (CI) 1.22–4.23; P = 0.009] and mechanical ventilation (HR 2.55, 95% CI 1.30–4.75; P = 0.003) at the time of transplantation to be predictive of poorer 30-day and long-term survival.

Lechiancole et al. [4] analysed 32 patients in refractory cardiogenic shock who were bridged with VA ECMO to heart transplantation at their institution between 2005 and 2017. Overall, these patients showed a high early post-transplant mortality (18.7% < 30 days). When stratified according the mean acute physiology, age and chronic health evaluation (APACHE IV) score, patients with a mean of 52.50 ± 6.85 had 26.6% 1-year survival, which compared negatively to the 89.7% 1-year survival in patients with a mean APACHE IV score of 31.90 ± 9.55. Authors concluded that an APACHE IV score could be considered a powerful predictor of survival, and can account for a better selection of patients on ECMO supported at the time of listing.

Fukuhara et al. [5] interrogated the UNOS database, and examined the outcomes of 25 168 adult heart transplant recipients between 2003 and 2016. The authors compared the results of 107 heart transplant recipients bridged with VA ECMO to the results of 6148 patients bridged to transplantation with a durable continuous-flow left ventricular assist device (LVAD). The Kaplan–Meier analysis of a propensity-matched cohort demonstrated lower survival in the ECMO group at 90 days (74.8% vs. 88.8%; P = 0.025) and 3 years (69.3% vs. 82.2%; P = 0.054). Multivariable logistic and Cox regression analyses showed the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score to be the sole predictor of both 90-day (odds ratio 1.94 per 5-point of increase, 95% CI 1.00–3.76; P = 0.05) and 3-year mortality (HR 1.47 per 5-point of increase, 95% CI 1.16–1.88; P = 0.002). Bridge to transplant with VA ECMO was associated with increased early and mid-term mortality, especially in patients with a MELD-XI score greater than 17, who demonstrated >50% 3-year mortality.

Barge-Caballero et al. [6] conducted a retrospective multi-institutional study (16 Spanish hospitals) of 129 patients who underwent heart transplantation directly from VA ECMO. The authors observed 33.3% in-hospital post-transplant mortality. Cox regression revealed age (HR 1.29 per 10-year of increase, 95% CI 1.06–1.56; P = 0.01), vasoactive-inotropic score (HR 1.07 per 10 units of increase, 95% CI 1.04–1.10; P < 0.001), serum lactate levels (HR 1.10, 95% CI 1.00–1.20; P = 0.049), active infection requiring therapy (HR 2.13, 95% CI 1.20–2.79; P = 0.01) and renal replacement therapy (HR 2.02, 95% CI 1.06–3.84; P = 0.032) at the time of listing as independent predictors of mortality.

Jasseron et al. [7] evaluated 46 heart transplant recipients bridged with VA ECMO reported to the French national registry between 1 January 2010 and 31 December 2011. Median duration of VA ECMO to transplantation was 9 days and 1-year post-transplant survival was 70%. Cox proportional hazard analysis showed age >50 years at listing to be a significant predictor of mortality (HR 2.4, 95% CI 1.1–5.1; P = 0.02).

Mishra et al. [8] reviewed their post-transplantation outcomes of 15 patients bridged with ECMO (ECHTx), 26 patients bridged with LVAD (LVADHTx) and 206 non-bridged patients during 2005–2012. One-year and 5-year survival rates were 70% and 70% for ECHTx, 96% and 83% for LVADHTx and 92% and 81% for HTx (overall survival, P ≤ 0.001).

Cho et al. [9] evaluated the outcome of 25 adult patients bridged to transplantation with ECMO from November 2004 to August 2013. Seven patients (28%) died within 1 year of transplantation. The MELD and sequential organ-failure assessment (SOFA) scores were found to be predictive of the adverse outcome regardless of the duration of ECMO.

CLINICAL BOTTOM LINE

Heart transplantation results of patients bridged with VA ECMO are inferior when compared to reported outcomes of patients bridged with durable LVADs as well as non-bridged recipients. Acuity of illness (reflected by high recipient APACHE, SOFA and/or MELD score), high serum lactate, mechanical ventilation at the time of transplantation, active infection and advanced age portend poor post-heart transplantation results.

Conflict of interest: none declared.

REFERENCES