Invited commentary on: Myocardial recovery in children supported with a durable ventricular assist device – a systematic approach

In this issue, Rohde et al. [1] published a systematic review on the important topic of myocardial recovery in children supported with a durable ventricular assist device (VAD).

With the improvements in advanced paediatric heart failure (HF) treatment, the conundrum is that the number of children on the transplant waiting list bridged with a durable VAD system is increasing [2], while we are struggling with the shortage of donor organs. Even though the long-term outcomes of paediatric cardiac transplantation (HTX) are continuously improving, the children still have to carry the burden of life-long immunosuppression with its chronic side effects. HTX therefore should remain the last option in case there is no chance of recovery.

Once the left ventricle is mechanically unloaded and cardiac output is restored a lot of maladaptive mechanisms of chronic HF can be reversed and may lead to myocardial functional recovery with improvements in myocardial size and contractility, mitochondrial function and a reduction in adrenergic overstimulation and apoptosis. The RESTAGE-HF multicentre prospective trial in adult patients showed that 47% of the selected patients with chronic HF achieved sufficient improvement of cardiac function to reach the criteria for LVAD explantation [3].

Assuming that the capacity of myocardial recovery especially in young children may be superior to adults, these are the children we do not want to miss.

The best option therefore would be the right timing of VAD weaning and explantation to prevent the adverse effects of long-term VAD therapy, such as stroke and haemorrhage, without the need of HTX. However, if we have a look at the authors systematic review of myocardial recovery in children supported with a durable VAD the overall recovery incidence rate in current literature is only 8.7% [1].

Furthermore, regarding long-term results, 15 of the 81 children (14%) died after VAD explantation, though only half of the deaths were cardiac related. Three children needed another VAD implantation and 2 patients needed HTX anyway. Thus transplant and event-free survival was reported in only 75% of the children. This is in contrast with the RESTAGE-HF Trial where the explantation survival free from LVAD or transplantation was 90% at 1 year and 77% at 2 and 3 years. But the adult trial also included a protocol of optimized LVAD mechanical unloading, combined with standardized specific pharmacological therapy to induce reverse remodelling [3]. A EUROMACS study on outcomes of adult patients after successful left VAD explantation reported an event-free survival of 88% after 2 years. In these patients, beta-blockers were prescribed to 85%, angiotensin-converting enzyme inhibitors to 71% and loop diuretics to 50% of the patients, respectively [4]. In the paediatric review, a lot of authors do not even mention medical therapy besides anticoagulation protocols on VAD. Miera et al. implemented a medical anticongestive HF therapy in all children during the early postoperative course from the year 2005 on and indeed the overall recovery rate (14%) and 10- and 15-year event-free survival rates were better than in most other paediatric studies [5]. With the recent advances in medical HF therapy and the approval of Sacubitril/valsartan for the management of HF in children by the European Medicines Agency this year, recovery rates may even improve with a complete and modern pharmacological HF therapy. The implementation of the anticongestive therapy in end-stage paediatric HF, quite often is only possible after cardiac output is reestablished mechanically during VAD therapy to avoid initial arterial hypotension and end-organ dysfunction.

Another important point in our opinion is, that some centres do not prospectively look for the evidence of potential myocardial recovery. The nature and aetiology of cardiomyopathy often remain unexplained even after endomyocardial biopsies (EMB). However, endomyocardial biopsies should be performed during implantation of the VAD, to get an idea about the degree of fibrosis or acute inflammation of the myocardium which has an impact on the reversibility of the myocardial damage.

An effective mechanical unloading of the left and consecutively the right ventricle should be examined weekly by echocardiography and measurement of NT-proBNP and pump speed should be optimized accordingly [6]. With the evidence of myocardial recovery where an increase in left ventricular ejection fraction and a reduction in left ventricular diastolic diameter, together with a decline in NT-proBNP is observed [6] even during a reduction in pump speed, a paediatric weaning protocol could be used to identify children for recovery and possibly explantation of the LVAD [5]. Especially in young children and those diagnosed with myocarditis the probability of recovery is the highest and long-term survival after weaning from the VAD may be better than after heart transplantation. Unfortunately, the systematic review of the current literature cannot tell us the impact of age, aetiology of HF or the best mode of mechanical unloading to achieve the possibly best probability of myocardial recovery in children. For example, left ventricular volume unloading seems to be pronounced in pulsatile LVADs [7] and theoretically coronary perfusion of the myocardium might be enhanced during pulsatile unloading of the ventricle.

In the future maybe not only clinical and echocardiographic parameters could be helpful to distinguish patients with potential myocardial recovery but also proteomic profiles of myocardial tissue samples [8].

In summary, after VAD implantation in children optimal left ventricular unloading should be ensured by a standardized echocardiographic protocol together with optimization of the pump settings. Reverse myocardial remodelling must be supported by a modern pharmacological therapy. Improvement of the myocardial function even under reduced VAD output, combined with a decline in NT-proBNP may be effective to identify possible candidates for a standardized LVAD explantation protocol. This approach could result in a higher incidence of LVAD explantation to achieve a transplant- and event-free survival in these children.

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