Extracorporeal membrane oxygenation for graft failure after heart transplantation: a multidisciplinary approach to maximize weaning rate

INTRODUCTION

The use of a veno-arterial extracorporeal membrane oxygenator (VA-ECMO) in severe primary graft failure (PGF) after heart transplantation (HTx) is widely accepted (1-2-3-4-5-6-7). ECMO allows right-chamber unloading and sufficient circulatory support, though left ventricle (LV) distension can occur, resulting in LV stasis, thrombosis and failure of the aortic valve to open (8-9). In PGF, the loss of LV compliance, but maintenance of mitral valve competence, leads to an increase in endoventricular pressure, a rise in wall tension, a decrease in coronary flow, and reduction in the rate of cardiac recovery (10).

Many surgical or percutaneous solutions have been described to relieve LV overload during ECMO support (mainly in non-PGF patients), though most are anecdotic, and still imply further risk of bleeding from puncture site, heart trauma or tamponade (11-12). A multidisciplinary assessment with the goal of preventing rather than treating ECMO-support-related complications can increase the recovery rate.

Since the start of our heart transplant program, in 2006, 114 transplants have been performed at our institute. Nineteen patients (16.6%) suffered from PGF, requiring a ventricle assist support device: one patient was assisted by a biventricular centrifugal pump, while the other 18 received VA-ECMO. These 18 patients were our study population.

The aim of our study was to analyze the role of a multidisciplinary approach to the prevention and detection of complications, cardiac recovery, and readiness for ECMO weaning in severe PGF patients.

MATERIALS AND METHODS

Approval of the Institutional Review Board was obtained. We retrospectively analyzed all patients who had undergone isolated HTx at our institute, and needed extracorporeal circulatory support for severe PGF. Severe PGF was defined, according to the International Society of Heart and Lung Transplantation consensus (13), as dependence on left or biventricular mechanical support including ECMO, LVAD, BiVAD, or percutaneous LVAD, despite the maximum medical management (included counterpulsation). The male/female ratio was 14/4, and the mean age was 49 ± 11 years. Body surface area and body mass index were 1.8 ± 0.3 m² and 26 ± 4, respectively. Donor and recipient characteristics are listed in Table I.

RESULTS

PGF was characterized mainly by right and left ventricle dysfunction and a mean LV ejection fraction of 15 ± 9% before initiation of ECMO. All ECMO supports were set up in the operating room after three failed attempts of weaning from CPB. The IABP could be placed in the operating room in 13 patients (72.2%), while 5 had anatomical contraindications (mainly small vessels or peripheral disease). The mean IABP support time was 9.2 ± 7.6 days. All patients received TEE monitoring, even those with no complications.

For ECMO support, 14 patients were supported using central cannulation, while 3 were peripherally cannulated, and one patient received central arterial cannulation and peripheral venous cannulation (for severe femoral artery calcification). Details of the extracorporeal support are shown in Table III. Mean ECMO flow was 4164 ± 679 l/min, and in four cases the flow spontaneously dropped to less than 2 l/min due to bleeding or cardiac tamponade, with the patient requiring urgent re-exploration.

The support achieved good end-organ perfusion, with reduction of lactate, creatinine, and SGOT (Tab. II).

DISCUSSION

Primary graft failure is one of the strongest risk factors for 30-day mortality after heart transplantation, with a slightly increasing incidence over the recent years, probably because of the extensive use of marginal donors (2-3). The rate of PGF after heart transplantation is reported as between 3% and 26%, with mortality between 20% and 50%, which is in line with our data (4-5-6-7, 16).

Both centrifugal pumps and ECMO have been extensively described in the treatment of PGF, with different approaches mainly determined by the expertise of the center. At present, ECMO is widely accepted for postcardiotomy and PGF, given the easier setup, the versatility, and the possibility of biventricular assistance and lung assistance with a single pump. Despite the obvious advantages in terms of end- organ perfusion, ECMO still carries a high risk of severe complications and mortality. Consequently, every effort should be made to guarantee appropriate flows, prevent the most life-threatening complications, such as intraventricular thrombosis and cardiac tamponade, and, overall, facilitate proper cardiac recovery.

Indeed, avoiding left ventricular distension and stasis during ECMO, ensuring that the aortic valve opens and some blood flows through the chambers, should be one of the principal goals, particularly when left ventricular function is severely compromised (8-9-10). This can be achieved with a continuous multidisciplinary approach involving intensivists, cardiologists, and surgeons. With severely compromised hemodynamics, it is not easy to strictly follow a general protocol, especially the goal of negative fluid balance. With a longitudinal analysis, we observed a kind of learning curve with more strict observation of some general principles, and identification of the roles of physicians in the management of the patients.

The responsibility of the intensivist is to achieve strict fluid balance to avoid fluid overload, the appropriate use of inodilators, and prompt communication with the ECMO team. TEE has become part of the management of monitoring ECMO, from the initiation of support to the decision to wean in order to detect complications before there is clinical evidence. Several echocardiography parameters, as well as an ejection fraction >35% to 40%, an LV outflow tract velocity-time integral >10 cm, absence of LV dilatation, the aortic valve opening rate, and, eventually, mitral regurgitation have been suggested as predictors of successful weaning (14, 17, 18). To the best of our knowledge, most of the echographic evaluations are reported for ECMO in decompensated heart failure (14-15), while PGF is a different condition, with specific patterns (19). So, given the high probability of recovery, making sure that the LV is well perfused but not overloaded, following the opening of the aortic valve and the LV dimension, and ruling out the most common complications can help improve the outcome.

Finally, the surgeon is integrated with the other physicians, and is responsible for the right timing of surgical revisions to reduce blood product transfusions, and for evacuation of pericardial collections before a drop in the flows and perfusion, which would necessitate an excessive use of vasoconstrictors.

With this approach, we have been able to ensure good cardiovascular support in all patients, with a significant reduction in lactate in the first 24 h, and a progressive normalization of the end-organ function test in most of the patients. The support has allowed almost 70% of the patients with PGF to recover heart function, and be weaned from support.

The role of IABP placement in aiding recovery is still a matter of debate. The beneficial effects of adding IABP support to VA ECMO on coronary perfusion and on reduction of the afterload have been well demonstrated in animal models (20-21), and single-center experiences have shown the efficacy in terms of outcome compared with no IABP use (22-23). Nevertheless, some have abandoned the use of IABP with ECMO because of the increased risk of vascular complications (16). Analyzing our data, in the group supported with IABP, the weaning rate was 84%, with a survival of 53%, while in the group without IABP the weaning rate was 40%, and the survival 20%. Moreover, analyzing the recovery of LV function patient by patient, the only two patients with no improvement in the ejection fraction were in the non-IABP group. Of course these data have no statistical weight, but still need to be considered. We found no other differences between the two groups, probably because the reduction in the afterload, and the increase in the coronary and pulsatile flows, offered by the IABP have a protective effect. In addition, we observed the effect of the absence and then of the presence of the IABP in the patient with the LV thrombosis. Initially the balloon was not placed because of some concerns about the size of the femoral vessels, then, after the trombectomy, the IABP was placed, and the aortic valve started to open, with no further occurrence of thrombi. It is likely that allowing even a small flow through the LV, reducing the afterload, and giving a pulsatile flow, can help the heart to recover.

Our study has several limitations. First, it is retrospective and non-controlled. Ideally, a prospective randomized trial would be indicated to better understand the impact of IABP placement on the outcome in PGF patients, though the nature of the pathology, with its inherently extreme hemodynamic instability would not allow for randomization and strict adherence to the two different protocols for IABP and non-IABP patients. Second, ventricular failure was not the same in all the patients: in some cases the right ventricle was worse than the left, so the role of IABP can become more questionable. Nonetheless, a multidisciplinary approach is still valid, and even when the right ventricle is worse than the left, the balloon helps increase the coronary perfusion of the right ventricle. Third, the rate of PGF requiring mechanical support in our series is higher than that reported in the literature, perhaps because of our extensive use of donors with high dosages of α-agonists and inotrops, as we reported in a previous, published study (24). Despite the fact that risks inherent in PGF are well known, the shortage of donors has increasingly worsened, and, like many centers, we have extended our criteria to accept marginal donors, particularly donors with high α-agonist or inotropic dosages.

In conclusion, a multidisciplinary approach, with routine use of an IABP, together with low doses of inotropic infusions and careful fluid management seems to help the recovery of the left ventricle after PGF. We may need a multicenter study, with a larger population, for more definitive results.

TEE monitoring of the right ECMO, from the initiation of support to the decision to wean, can help detect complications before there is clinical evidence. In PGF, recovery is usually more frequent than in other cases of postcardiotomy syndrome, due to the more probable reversibility of the damage, which is why weaning should be the first goal upon initiation of ECMO support.