Commentary: Ventricular recovery with left ventricular assist device support: The failed quest for the Holy Grail?

Central MessageTrue recovery with LVAD support still has a long way to go.See Article page 1. True recovery with LVAD support still has a long way to go. See Article page 1. Among the major areas of excitement surrounding the use of pulsatile left ventricular assist devices (LVADs) for heart failure was the initial observation of reverse remodeling of the LV in patients who were supported with these devices as a bridge to transplantation.1Levin H.R. Oz M.C. Chen J.M. Packer M. Rose E.A. Burkhoff D. Reversal of chronic ventricular dilation in patients with end-stage cardiomyopathy by prolonged mechanical unloading.Circulation. 1995; 91: 2717-2720Crossref PubMed Scopus (349) Google Scholar This ex vivo evaluation of explanted hearts suggested that with sufficient hemodynamic unloading of the LV, reversal of chamber enlargement can possibly be achieved. In some ways, this may have been the beginning of the quest for the Holy Grail; the possibility that given enough time, volume and pressure unloading of the LV may lead to recovery. Ideally, this would permit explanation of the LVAD and obviate the need for either prolonged VAD support or heart transplantation. Rao and Billia2Rao V. Billia F. Myocardial recovery following durable left ventricular assist device support.J Thorac Cardiovasc Surg Open. 2021; 8: 1-5Scopus (2) Google Scholar have provided a review of the status of heart recovery with durable LVAD support. As they mention, the first major clinical report suggesting this possibility was out of England, where the authors make use of the addition of clenbuterol, a beta2-adrenergic antagonist that promoted muscle hypertrophy, to allow for myocardial recovery. Unfortunately, the amazing results from that study have yet to be reproduced. Many protocols for evaluating LV recovery for explantation have been developed. These typically are initiated following uptitration of standard heart failure pharmacologic therapies as tolerated. Patients are then evaluated by a variety of modalities to assess recovery. In most circumstances, the pump is allowed to run at the lowest speed possible, and then an echocardiographic assessment and invasive hemodynamic evaluation are performed. In some situations, even exercise testing is performed at low speeds with continuous monitoring with the goal of ensuring that the patient has, in fact recovered. Despite these efforts, many surgeons have faced the dreaded reality of a crashing patient after device explant. Unfortunately, the field has not advanced as one would hope: Real-world data from the Interagency Registry for Mechanically Assisted Circulatory Support Registry reported only 5% success. If LV recovery and explantation is the Holy Grail, why are we yet to see better results? Perhaps part of the explanation is in the heterogeneous populations that have been studied and reported on to date. Many datasets have combined a mixture of etiologies of cardiomyopathies broadly defined as dilated or ischemic. In addition, true volume and pressure unloading of the heart was different with the older pulsatile pumps as opposed to the current continuous-flow pumps. It is not uncommon that one observes a decoupling of the pressure unloading and volume unloading with the current continuous pumps, so that despite a lower end-diastolic pressure, the LV still appears dilated at high operating speeds. In an elegant article by Kato and colleagues,3Kato T.S. Chokshi A. Parvati Singh P. Khawaja T. Cheema F. Akashi H. et al.Effects of continuous-flow versus pulsatile-flow left ventricular assist devices on myocardial unloading and remodeling.Circ Heart Fail. 2011; 4: 546-553Crossref PubMed Scopus (112) Google Scholar comparing pulsatile versus continuous-flow pumps, they observed that mechanical unloading of the LV is much more effective with the former, as evidenced by echocardiographic measurements and markers of extracellular matrix. This is not surprising in the case that one appreciates the different mechanisms of how these 2 pump systems work. Finally, in an attempt to enhance myocardial recovery, various trials with stem cells have been conducted. Again, these trials have failed, as one might expect given the profound lack of appreciation of what is the best type of cells, route of delivery, location and distribution of cells, and the quantity of cells that should be administered. In addition, the exact mechanism of how these stem cells contribute to recovery has never been elucidated. Whereas myocardial recovery after durable LVAD support has many theoretical advantages, at the moment we lack clarity about how to appropriately select patients and when to proceed with explantation. This article is a great summary of what has been done to date and outlines opportunities for future studies. It seems likely that better adjunctive reparative measures will be necessary before more widespread adoption is possible. Myocardial recovery following durable left ventricular assist device supportJTCVS OpenVol. 8PreviewDurable left ventricular assist device (LVAD) support as a bridge to recovery leading to LVAD explantation remains the holy grail of advanced therapies for heart failure. Although pharmacologic therapy using the Harefield Protocol with Clenbuterol (a β2 agonist) resulted in device explant in more than two-thirds of patients, these results have not been widely reproducible.1,2 Full-Text PDF Open Access