Outcome of mechanical cardiac support in children using more than one modality as a bridge to heart transplantation ^†

Abstract

OBJECTIVES

Mechanical cardiac support (MCS) can successfully be applied as a bridging strategy for heart transplantation (OHTx) in children with life-threatening heart failure. Emergent use of MCS is often required before establishing the likelihood of OHTx. This can require bridge-to-bridge strategies to increase survival on the waiting list. We compared the outcome of children with heart failure who underwent single MCS with those who required multiple MCS as a bridge to OHTx.

METHODS

A retrospective study of patients aged less than 16 years was conducted. From March 1998 to October 2005, we used either a veno-arterial extracorporeal membrane oxygenator (VA-ECMO), or the Medos® para-corporeal ventricular assist device (VAD). From November 2005 onwards, the Berlin Heart EXCOR® (BHE) device was implanted in the majority of cases. Several combinations of bridge-to-bridge strategies have been used: VA-ECMO and then conversion to BHE; BHE and then conversion to VA-ECMO; left VAD and then upgraded to biventricular support (BIVAD); conversion from pulsatile to continuous-flow pumps.

RESULTS

A total of 92 patients received MCS with the intent to bridge to OHTx, including 21 (23%) supported with more than one modality . The mean age and weight at support was similar in both groups, but multimodality MCS was used more often in infancy ( P = 0.008) and in children less than 10 kg in weight ( P = 0.02). The mean duration of support was longer in the multiple MCS group: 40 ± 48 vs 84 ± 43 days ( P = 0.0003). Usage of multimodality MCS in dilated cardiomyopathy (19%) and in other diagnoses (29%) was comparable. Incidence of major morbidity (haematological sequelae, cerebrovascular events and sepsis) was similar in both groups. Survival to OHTx/explantation of the device (recovery) and survival to discharge did not differ between single MCS and multiple MCS groups (78 vs 81% and 72 vs 76%, respectively).

CONCLUSION

Bridge to OHTx with multiple MCS does not seem to influence the outcome in our population. Infancy and body weight less than 10 kg do not tend to produce higher mortality in the multiple MCS group. However, children receiving more than one modality are supported for longer durations.

Heart failure, Mechanical circulatory support, ECMO, Heart transplantation, Paediatrics

INTRODUCTION

Mechanical cardiac support (MCS) has been used increasingly during the last two decades to bridge children with life-threatening heart failure to heart transplantation (OHTx) [ 1–4 ].

A bridge-to-bridge strategy is sometimes required when a child presents emergently ‘in extremis’ and uncertainty occurs about the decision to commit to MCS as a bridge to OHTx as major comorbidity such as neurological status, respiratory failure, overwhelming infection, visceral ischaemia or renal failure may be present. There may also be uncertainty regarding diagnosis or suitability for OHTx. In the interim, children with catastrophically failing circulation need support, but before committing to MCS with a ventricular assist device (VAD), short-/medium-term assistance with a veno-arterial extracorporeal membrane oxygenator (VA-ECMO) [ 5 , 6 ] or continuous-flow pumps can be offered as a bridge to decision [ 7 ]. The latter require less invasive cannulation than a VAD and licence for use is up to an 1-month duration. This gives more time to assess the suitability of the patient for transplant and to plan elective long-term VAD implantation.

Complications occurring after mechanical assist device implantation may require refashioning of circulatory support, for example upgrading to a biventricular device, changing to a different type of flow (continuous versus pulsatile) [ 8 ] or adding an extracorporeal membrane oxygenator in the system.

During 15 years of experience with MCS, a significant proportion of patients required multimodality MCS as a bridge to OHTx, either in single or in multiple episodes. In this study, we have sought to compare the outcome of children receiving MCS with a single modality with those who required multiple modes.

METHODS

Institutional Review Board approval was obtained for the study and the board waived the need for individual patient parental consent. The database of all patients less than 16 years of age who underwent MCS was retrospectively reviewed and stratified by diagnosis. The experience of MCS in congenital heart disease has previously been reported and then excluded from this analysis [ 9 ].

Since the bridge to transplantation programme started at our institution in 1998, Freeman Hospital has become one of the only two national centres that undertake mechanical support in the paediatric population in the UK. It not only provides transplant assessment and VAD implantation, but also routinely accepts patients who have sustained cardiac arrest and had extracorporeal cardiopulmonary resuscitation commenced elsewhere. At the beginning of our experience, VA-ECMO was predominantly used. Subsequently, a few Medos® HIA (Medos Medizintechnik AG, Stolberg, Germany) para-corporeal VADs were implanted in children, and since November 2005 the Berlin Heart EXCOR® (BHE; Berlin Heart GmbH, Berlin, Germany) has become the device of first choice for long-term mechanical support and was implanted in the majority of cases. Several combinations of bridge-to-bridge strategies have been used: initial VA-ECMO for the acutely ill children and thereafter conversion to a BHE device for prolongation of support; initial BHE implantation as a left VAD (LVAD) and then a subsequent upgrade to biventricular support (BIVAD) due to persistent right ventricular failure; initial BHE implantation and then conversion to VA-ECMO due to lung function deterioration; conversion from pulsatile-flow VADs to continuous-flow pumps or vice versa . The Levitronix PediVas® (Thoratec, Pleasanton, CA, USA) was used in case of persistent thrombotic complications.

Our surgical strategies of VA-ECMO cannulation and BHE device implantation have already been extensively described, as well as the protocol of VAD care [ 9 ].

Patients

Between November 1998 and June 2014, a total of 92 children required MCS with the intention of bridging to OHTx, 21 of them (23%) receiving more than one MCS modality. Table 1 details the circulatory support and outcome by the type of device in the single MCS modality population: the majority of the patients, 43, were supported with the BHE device, followed by VA-ECMO in 17, Medos® HIA in 6 and Levitronix PediVas® in 5. Forty-seven children required support for heart failure in the context of dilated cardiomyopathy (DCM), and 24 for diagnoses other than DCM (8 myocarditis, 8 post transplant rejection, 3 neonatal myocardial infarction, 2 restrictive cardiomyopathy, 1 hypertrophic cardiomyopathy, 1 arrhythmogenic cardiomyopathy and 1 post chemotherapy).

Table 1:

Single MCS population

n	Survival to OHTx or recovery	Death during MCS
71 (100%)	55 (78%)	16 (22%)
BHE = 43	BHE = 36 (32 OHTx and 4 recovery)	BHE = 7
VA-ECMO = 17	VA-ECMO = 11 (9 OHTx and 2 recovery)	VA-ECMO = 6
Medos = 6	Medos = 3 (3 OHTx)	Medos = 3
Levitronix = 5	Levitronix = 5 (4 OHTx and 1 recovery)	Levitronix = 0

MCS: mechanical cardiac support; BHE: Berlin Heart EXCOR; VA-ECMO: veno-arterial extracorporeal membrane oxygenator; OHTx: orthotopic heart transplantation.

Combinations of MCS used in the multiple modalities group are detailed in Table 2 and Fig. 1 . Five children required multiple MCS in separate but consecutive episodes before reaching OHTx. Patients 7° [ 10 ] and 21° received three different episodes, with a total length on support of 82 and 184 days, respectively; the time off from MCS between first and second episodes was 57 and 70 days, and between second and third was 120 and 13 days, respectively. Patients 12°, 13° and 15° received two different episodes, with a total length on support of 42, 123 and 100 days, respectively; the time off from MCS between first and second episodes was 28, 67 and 94 days, respectively. None of these children have been removed from the transplant list during the support-free intervals. Eleven children had mechanical support for heart failure secondary to DCM, and 10 for diagnoses other than DCM (5 myocarditis, 3 post chemotherapy, 1 post transplant rejection and 1 hypertrophic cardiomyopathy).

Table 2:

Multiple MCS population

No.	Age (months)	Diagnosis	Cardiac arrest pre-MCS	MCS (type)	Total length of support (days)	Outcome
1.	36	Post chemotherapy	Yes	VA-ECMO → BIVAD (BHE)	73	Transplant
2.	190	Post chemotherapy	No	LVAD (BHE) → BIVAD (BHE)	42	Transplant
3.	3	DCM	No	VA-ECMO → LVAD (BHE) → BIVAD (BHE)	134	Transplant
4.	46	DCM	No	VA-ECMO → BIVAD (BHE)	54	Transplant
5.	8	Myocarditis	Yes	VA-ECMO → BIVAD (BHE)	123	Explant
6.	90	DCM	Yes	VA-ECMO → BIVAD (BHE)	27	Transplant a
7.	48	DCM	Yes	LVAD (BHE) → Explant BIVAD (BHE) → Explant VA-ECMO → LVAD (BHE)	82	Transplant
8.	28	Post chemotherapy	Yes	LVAD (BHE) → BIVAD (BHE)	74	Transplant
9.	7	Myocarditis	No	LVAD (BHE) → BIVAD (BHE)	51	Transplant
10.	203	Acute graft failure	Yes	VA-ECMO → BIVAD (BHE)	43	Explant
11.	6	DCM	No	VA-ECMO → LVAD (BHE)	54	Transplant
12.	8	Myocarditis	No	LVAD (BHE) → Explant LVAD (BHE)	42	Transplant
13.	8	DCM	Yes	LVAD (BHE) → Explant BIVAD (BHE)	123	Transplant
14.	10	DCM	Yes	VA-ECMO → BIVAD (BHE) → VA-ECMO → BIVAD (BHE)	72	Death
15.	10	DCM	No	LVAD (BHE) → Explant LVAD (PediVas) → LVAD (BHE)	100	Transplant
16.	9	Myocarditis	No	LVAD (BHE) → BIVAD (PediVas)	140	Transplant
17.	16	DCM	No	BIVAD (BHE) → VA-ECMO	119	Death
18.	8	HCM	Yes	BIVAD (BHE) → VA-ECMO → BIVAD (PediVas)	47	Death
19.	6	DCM	No	LVAD (BHE) → LVAD (PediVas)	42	Transplant
20.	1	Myocarditis	No	LVAD (BHE) → BIVAD (BHE) → BIVAD (PediVas) → VA-ECMO	153	Death
21.	5	DCM	No	VA-ECMO → Explant LVAD (PediVas) → LVAD (BHE) → Explant LVAD (BHE)	184	Transplant

MCS: mechanical cardiac support; DCM: dilated cardiomyopathy; HCM: hypertrophic cardiomyopathy; VA-ECMO: veno-arterial extracorporeal membrane oxygenator; BIVAD: biventricular assist device; LVAD: left ventricular assist device; BHE: Berlin Heart EXCOR.

^a Hospital death after transplant.

Figure 1:

Flowchart of the outcome in the multimodality mechanical cardiac support group. MCS: mechanical cardiac support; VA-ECMO: veno-arterial extracorporeal membrane oxygenator; VAD: ventricular assist device; OHTx: orthotopic heart transplantation; LVAD: left ventricular assist device; BIVAD: biventricular assist device.

All children were followed from the time of MCS implantation and censored at the time of recovery/explantation (removal from the waiting list), death during support (death while awaiting OHTx), OHTx leading to death before discharge and OHTx with survival to hospital discharge. Outcomes of patients receiving single and multiple MCS were compared in terms of major complications (stroke, chest exploration for bleeding and sepsis), survival to OHTx, or recovery, and survival to hospital discharge. Major bleeding was defined as an episode of haemorrhage requiring reoperation and blood transfusion; and sepsis was considered as evidence of systemic involvement by infection manifested by positive blood culture and/or hypotension [ 1 ].

Statistical analysis

Continuous data are presented as mean ± standard deviation, reporting a confidence interval at 95%, and are compared with Student's t -test. Categorical data are expressed as proportions and compared with Fisher's exact test. A P -value of <0.05 is taken as significant. Analyses were performed using the software STATA v 11.0.

RESULTS

Demographic details are given in Table 3 . Children requiring multiple MCS tended to be younger at the time of MCS implantation. The proportion of infants receiving multimodality MCS was larger ( P = 0.008). Weight at the time of circulatory support was similar in both the groups. An increased use of multimodality MCS was noted in children with less than 10 kg of body weight ( P = 0.02). Table 2 describes the demographic characteristics, the diagnosis, the types of MCS and the outcome of each individual patient requiring multiple mechanical support modalities. Prior episodes of cardiac arrest requiring cardiopulmonary resuscitation occurred with similar statistical frequency in both groups. The mean overall length of support on the mechanical circulation was twice as long in multiple MCS modalities population ( P = 0.0003), with a peak of 244 days in an infant on BIVAD affected by DCM, in the single MCS modality group, and 183 days in a child with DCM that required three different consecutive episodes of MCS before reaching OHTx. There was a non-significant increased use of multiple MCS modalities in diagnosis other than DCM (Table 3 ).

Table 3:

Demography

	Single MCS modality ( n = 71)	Multiple MCS modalities ( n = 21)	P -value
Age at MCS (months)	61 ± 64 (CI 95% ± 14.8)	35 ± 52 (CI 95% ± 22.4)	0.1 a
<1 year	20 (28%)	13 (62%)	0.008 b
1–10 years	36 (50%)	6 (28%)
>10 years	15 (34%)	2 (10%)
Weight at MCS (kg)	20 ± 19 (CI 95% ± 4.4)	13 ± 12 (CI 95% ± 5.1)	0.08 a
<10 kg	30 (42%)	15 (71%)	0.02 b
Pre-MCS cardiac arrest	22 (31%)	9 (43%)	0.4 b
Overall length on MCS (days)	40 ± 48 (CI 95% ± 11.1)	84 ± 43 (CI 95% ± 14.9)	0.0003 a
DMC	47 (66%)	11 (52%)	0.2 b
Other diagnosis	24 (34%)	10 (48%)

MCS: mechanical circulatory support; DCM: dilated cardiomyopathy.

^a Student's t -test.

^b Fisher's exact two-tailed test.

Morbidity and mortality of patients who underwent single and multiple MCS modalities are compared (Table 4 ). The incidence of cerebrovascular events (CVA; 25 vs 33%), chest exploration for bleeding (21 vs 38%) and sepsis (24 vs 28%) during the MCS did not quite reach statistical difference between the two groups. In the multimodality MCS population, 2 children experienced a CVA related to cardiac arrest before the MCS, whereas 7 (28%) sustained a stroke during support (thromboembolic in 5 and haemorrhagic in 2). Eight patients (38%) experienced a major episode of bleeding and 6 required chest re-exploration. In 3 of the latter (patients 13°, 15° and 16°, Table 2 ), a factory-made Berlin Heart arterial cannula with a GoreTex armed graft extension (BH CGRG-021) was implanted: all of them required emergency chest exploration for cardiac tamponade due to a seroma through the graft material and replacement of the arterial cannula.

Table 4:

Overall outcome of single versus multiple MCS

	Single MCS modality ( n = 71)	Multiple MCS modalities ( n = 21)	P- value
CVA during MCS	18 (25%)	7 (33%)	0.6 a
Major bleeding during MCS	15 (21%)	8 (38%)	0.1 a
Sepsis during MCS	17 (24%)	6 (28%)	0.8 a
Died on MCS	16 (23%)	4 (19%)	0.7 a
Explanted	6 (8%)	2 (10%)
Transplanted	49 (69%)	15 (71%)
Post OHTx VA-ECMO support	7/49 (14%)	2/15 (13%)
Survival to hospital discharge	51 (72%)	16 (76%)	0.7 a
Infant mortality (<1 year of age)	5/20 (25%)	3/13 (23%)	>0.99 a
Mortality for weight <10 kg	8/30 (27%)	4/15 (27%)	>0.99 a

MCS: mechanical circulatory support; OHTx: orthotopic heart transplantation; CVA: cerebrovascular accident; VA-ECMO: veno-arterial extracorporeal membrane oxygenator.

^a Fisher's exact two-tailed test.

Eight children successfully recovered allowing explantation of the device, 6 (8%) in the single MCS group and 2 (10%) in the multiple MCS group. Of the latter, 1 child recovered good ventricular function following myocarditis after a total of 123 days on support (1 week on VA-ECMO and 4 months on BIVAD BHE); the second patient was mechanically assisted for rejection after OHTx and recovered after a total of 43 days (1 week on VA-ECMO and 1 month on BIVAD BHE). Of 64 children, 49 (69%) in the single MCS group and 15 (71%) in the multiple MCS group were successfully bridged to OHTx. Of 20 patients, 16 (23%) in the single MCS group and 4 (19%) in the multiple MCS group died during mechanical support. In the multimodality MCS population, the cause of death was multiorgan failure in 3 and haemorrhagic stroke in 1. All 7 children bridged with VA-ECMO to a VAD survived to OHTx, while all 4 who required VA-ECMO at some stage post VAD died on MCS (Table 2 and Fig. 1 ). All 5 patients receiving multiple MCS modalities in separate episodes reached successful OHTx (Table 2 and Fig. 1 ). Two children required a second run of MCS with VA-ECMO after OHTx: the first was a 7–year-old girl (Patient 6°, Table 2 ) who died after 8 days of VA-ECMO for cerebral haemorrhage; the second was a 5–month-old infant (Patient 21°, Table 2 ) who was successfully weaned after 5 days on VA-ECMO support.

The overall survival rate to recovery/transplantation was 77% and the survival rate to discharge was 73% in patients receiving MCS. Both survival to recovery/transplantation (78 vs 81%) and survival to discharge (72 vs 76%) did not differ significantly comparing the single and the multiple MCS groups, respectively. The mortality rates for MCS in infancy and in children under 10 kg of body weight were superimposable (25 vs 23% and 27 vs 27% in the single and multiple MCS population, respectively; Table 4 ).

DISCUSSION

This study retrospectively reviews 92 paediatric patients supported with MCS as a bridge to OHTx over the last 15 years. The main purpose is to evaluate the impact on early outcome of children assisted with more than one modality of MCS.

As our institutional experience also reflects, the advent of BHE and its improvement in technology, implantation techniques and anticoagulation management [ 1–4 ] significantly changed the life expectancy of children with heart failure; this is superior to VA-ECMO in length, quality of support and outcome [ 6 ]. Moreover, despite a non-negligible morbidity rate [ 1–4 ], the possibility to prolong the length of support and the significant rate of successful explantation with long-term VAD [ 11 ] has proven to be crucial in the modern era, given the constantly decreasing number of paediatric heart donors worldwide [ 12–14 ].

Children presenting acutely with cardiogenic shock still remain a challenge, as their survival could be rapidly compromised. Acute and catastrophic heart failure make the decision to commit to MCS more difficult, because uncertainty prevails both with regard to the underlying diagnosis and the severity of morbidity associated with the peri-arrest period. VA-ECMO still remains the most useful life-saving approach for acutely failing circulation, offering immediate haemodynamic stability while giving the opportunity to assess suitability for long-term VAD support as a bridge to decision [ 5 , 6 ]. Interestingly, in this study, the use of multimodality MCS in the paediatric population did not affect survival to OHTx or 30-day survival post OHTx. Moreover, according to other large international experiences [ 1–3 ], the use of VA-ECMO as a bridge strategy to long-term VAD implantation did not produce further mortality. The bridge to long-term VAD has been always completed within a week from the initial VA-ECMO support, the time necessary to clarify the underlying diagnosis and assess the peri-arrest period morbidities (neurological sequelae, lung disease, infection, renal impairment and visceral ischaemia) that could preclude the suitability for heart transplantation. Since we started our first VA-ECMO as ‘bridge to a bridge’ strategy in 2005, all 7 children requiring extracorporeal life support before BHE survived to transplantation or explantation of the device.

On the contrary, the only unfavourable outcome in this study occurred in all the children needing a step-back to VA-ECMO after durable BHE support and then dying on MCS. The average time of conversion to VA-ECMO was longer than a month, underlining the absolutely stable initial course on MCS and confirming the right indication to primarily assist these children with long-term devices as a bridge to OHTx. These data reflect the sickest nature and the bad prognosis for OHTx of MCS patients who develop irreversible deterioration of lung function and associated severe hypoxia. As a consequence of that, in our series, 3 of the 4 children at some stage VA-ECMO post VAD died of multiorgan failure. The other child was affected by hypertrophic cardiomyopathy and required multiple revisions of the cannulation sites because of poor VAD drainage: despite a first step back to VA-ECMO and subsequent technically successful conversion to a continuous-flow BIVAD, the patient died from the consequences of a haemorrhagic stroke.

The upgrading to a BIVAD from an initial single LVAD was necessary in 4 patients. It represents a small percentage of all our MCS cases and reflects the early years of our BHE era. The accurate assessment of the right heart performance in the context of heart failure still requires experience as an inadequate right ventricle can seriously compromise LVAD pump function. Our children had a prompt right BHE ventricle insertion after a mean time of 4 days, and the biventricular upgrading did not produce any additional mortality reaching the OHTx.

The recovery of good heart function after long-term MCS in the context of primary or secondary cardiomyopathy is a success of the modern era [ 11 ]. However, recurrence or persistence of significant ventricular dysfunction may lead to subsequent new settings of MCS. Five children in this experience required multiple separate but consecutive episodes of MCS, following relapse to heart failure after previous temporary successful explantation of the device. But interestingly, the need to establish different episodes of MCS did not appear to influence the ultimate outcome, as all those children were successfully bridged to OHTx and survived to hospital discharge. The latter observation can exceedingly push to try to explant the device of the heart, suggesting that even multiple episodes of MCS alternating with short periods of restored ventricular function can be well tolerated and it does not seem to compromise the chance of OHTx and survival [ 11 ].

Younger age and low weight at the time of MCS with BHE are recognized as risk factors for mortality in large single-centre and multicentre studies [ 1–4 , 15 ]. Similarly, our experience shows an average mortality rate of 25% during MCS in infants less than 1 year of age and up to 27% in children with less the 10 kg of body weight. A significant greater number have been assisted with multimodality MCS, but surprisingly it did not reduce the rate of OHTx in infancy, suggesting a non-incremental risk in mortality compared with the same age single MCS modality population.

Morbidity persists as a significant clinical problem in paediatric MCS. Although not statistically significant, children receiving multimodality MCS had higher rates of CVA, episodes of major bleeding and infection compared with the single MCS modality. This is related firstly to a longer length of support and, in addition, to the need to do several revisions of the MCS that can require multiple manipulations of the vessels and numerous re-entries into the chest. The management of anticoagulation therapy again remains an unresolved significant problem, since the right equilibrium between clotting and bleeding is difficult to achieve. Despite a meticulous approach to the latter, stroke still represents the leading cause of death as in most series [ 1–4 ].

As a final comment, in our experience the use of multimodality MCS has resulted in a safe longer mean length on support, pointing out again that it could be a good strategy to increase the number of children with end-stage heart failure who can be bridged successfully to OHTx, prolonging the ‘waiting game’ [ 14 ]. Nevertheless, this observation further highlights the decreasing number of OHTx, in the paediatric population due to the lack of donor organs and encourages accepting hearts with known poor function and electively supporting them to recovery with ECMO post transplant [ 16 ].

In conclusion, the present clinical experience suggests that a bridge to OHTx using more than one modality of MCS does not alter the overall likelihood of a successful outcome, defined as recovery of cardiac function or OHTx. Despite a significantly increased requirement of multimodality support in children less than 1 year of age and with less than 10 kg of body weight, it does not appear to be a risk factor for mortality in infancy. However, children receiving multiple modalities of MCS are supported for a significantly longer duration. This latter observation may reflect longer donor organ waiting times in the modern era compared with the early years of our programme: in fact, it was 2005 when the first use of ECMO as a ‘bridge to a bridge’ strategy was used.

Conflict of interest: Fabrizio De Rita, Simon Haynes and Massimo Griselli are supported by Berlin Heart GmbH, Berlin, Germany.

APPENDIX. CONFERENCE DISCUSSION

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Dr B. Alsoufi(Atlanta, GA, USA): When you are talking about bridge to bridge, you have combined multiple modalities, multiple scenarios. The most interesting group is the group of patients who started with VA-ECMO and were eventually switched to a VAD, and you have excellent results with 100% survival, which is better than what is reported in many other reports.

My first question is what are your criteria to switch from VA-ECMO to VAD and how do you explain your superior results? I am not sure that I would combine those patients together. Patients who started with VA-ECMO and went to VAD are different from patients who started with a VAD and prove that they need BIVAD or VA-ECMO. So I think combining those patients together, even though it increases your patient cohort, also limited your ability to come with any useful conclusion. However, I am interested in those nine patients who either started with a VAD and switched to VA-ECMO or started with a VAD and switched to a BIVAD. What was the interval between the initial operation and the additional assist device, should they have received BIVAD from the beginning? What have you learned from your experience?

And finally, what I found is that you have a much longer waiting period in those patients who had multiple modalities. I am wondering, is it because you take them temporarily off the transplantation list? Is it because of the higher incidence of sensitization that they would wait longer for a suitable heart? Do you have any information about that, why do they need to stay longer on the waiting list?

Dr De Rita: Regarding the first question, we had very good results starting with VA-ECMO and then converting to long-term support with the Berlin Heart. VA-ECMO implantation allowed us to clarify the diagnosis, so that if the patient is suitable for transplantation and he didn't experience any event that could be a contraindication for transplantation, we are quite aggressive in switching the ECMO to long-term support sooner rather than later, and we try to do it within a week. We improved over time, trying to have a very short period of time between the ECMO and the long-term ventricular assist device.

Regarding the second question, I know these patients affected the results of this study, because all children that had the initial implantation of a ventricular assist device, the Berlin Heart, and then required VA-ECMO implantation due to lung deterioration died and didn't reach transplantation. And I think that if during mechanical support, they start to develop complications related to the lungs or multi-organ failure, it is basically impossible to bridge successfully to transplantation – and this is what we have learned with the experience. So when you are forced to add an oxygenator in the circuit or to switch a patient with a VAD to ECMO, the outcome is not good.

Dr Alsoufi: What is the interval between the initial implantation and adding ECMO or adding a right VAD?

Dr De Rita: The mean time was about a month.

Dr Alsoufi: Not earlier?

Dr De Rita: Yes. I think because they were particularly sick patients from the beginning, so they didn't satisfy the proper characteristics to reach successful transplantation.

Dr Alsoufi: I am surprised it is that long. I was expecting it to be much shorter. That is why I was interested in your decision-making; did they need a BIVAD to begin with? How about the PRA? Why did they stay longer on the list?

Dr De Rita: One of the reasons the length of support is longer in the multimodality group is because the data are influenced by the fact that five patients had consecutive but separate episodes of mechanical cardiac support. We started late in our program to see if we could successfully wean patients from the VAD, because with a shortage of donor organs, sometimes it is not possible to bridge successfully to transplantation.

Initially we published our experience with one patient, who we thought was an exceptional case that had three separate runs of mechanical cardiac support before reaching transplantation and has been weaned from the device two times.

At the end of this study, I saw that we had five patients like this, and all of them reached transplantation successfully, and all of them did survive to hospital discharge. So I think the length of support is particularly influenced by this kind of management. We want to try, when possible, to wean off the device, and of course, we created a protocol in Newcastle for that.

Dr R. Cesnjevar(Erlangen, Germany): In the multimodality group, you switched patients from a BIVAD to a PediVas, could you stress a bit on the indication when you do this? Was it an inadequate pump size for the patient beforehand, or what was the problem?

Dr De Rita: It was primarily a clotting problem. Some patients required too many Berlin Heart pump changes, so we decided temporarily to switch to a continuous flow that, in our experience, is easier to manage with anticoagulation because we can measure the ACT and leave them on heparin for a while and restore proper anticoagulation.

Dr M. Hübler(Zurich, Switzerland): What is your cannulation policy? Do you go for peripheral venoarterial ECMO cannulation or do you do central cannulation? Do you use Berlin Heart cannulas for cannulation for the ECMO?

Dr De Rita: I think we did all of these types of settings. The first choice, of course, is to go peripherally. On some occasions, we put patients on ECMO with a Berlin Heart cannula in a way that enabled us to do the second stage, to switch to long-term support VAD, the only thing to do is to implant the ventricle, without the need to reopen the chest.

Author notes

†

Presented at the 28th Annual Meeting of the European Association for Cardio-Thoracic Surgery, Milan, Italy, 11–15 October 2014.