Although heart transplantation (HT) volumes have increased recently,1 continuous-flow (CF) left ventricular (LV) assist device (LVAD) implantation continues to be a vitally important therapeutic strategy for end-stage heart failure (ESHF). Due to the substantial excess of ESHF patients relative to donor organ supply, treatment of the total ESHF population will require expansion of durable mechanical circulatory support (MCS) approaches. However, several complications resulting from CF LVAD therapy, or pathologies that CF LVAD therapy does not address, challenge long-term outcomes.
In this background, in this issue of ASAIO Journal, Chou et al.2 report institutional outcomes with multiple LVAD exchanges. We provide perspective on this study and review strategies to treat a range of conditions termed “VAD failure” for the purposes of discussion.
VADs are designed to support or replace ventricular function and, consequently, to unload the relevant ventricle(s). Impairments in the safe performance of this task may occur due to improper medical management of loading conditions and CF LVAD parameters (affecting left-sided cardiac valvular and right ventricular function) and anticoagulation, CF LVAD dysfunction due to poor surgical planning or intraoperative technique, device dysfunction intrinsic to the CF LVAD components, device dysfunction due to pump thrombosis, and complications unique to CF LVAD therapy. Of these, the last 3 should be viewed as CF LVAD related, because they have a substantial rate of occurrence despite current “best practices.” Thus, in our view, CF LVAD component malfunction, pump thrombosis, device/driveline infections, stroke when anticoagulation is apparently therapeutic, and gastrointestinal bleeding due to acquired arteriovenous malformations, all should be viewed as “VAD failure.”
Chou et al.2 adopt a similar view to ours, vis-à-vis patients undergoing multiple LVAD exchanges. Over a 13 year period, within a subgroup of CF LVAD recipients who had already undergone a device exchange, 25 patients were treated with additional device exchange(s). Indications for repeat exchange included device malfunction (n = 14), pump thrombosis (n = 8), and device-related infection (n = 3). Hospital mortality was 32% (8/25); one patient died after a postdevice exchange HT. Five additional deaths occurred during the follow-up period. At the time of follow-up, a total of 13 patients had died, 9 patients were maintained on LVAD support, and 3 patients had undergone HT (including the patient who died).
It is evident from this study and others that patients undergoing device exchange have high short- and long-term mortalities and that subsequent device exchanges pose additional risks. However, operative therapeutic strategies other than device exchange exist. The remainder of our discussion will focus on comparisons between three surgical treatment options: CF LVAD exchange, device explantation, and HT (Figure 1). Of note, we will not discuss nonoperative management strategies, due to the poor results of these approaches.3
Option 1: Device Exchange…and Exchange…and Exchange
In some ways, device exchange requires the least thought, because it is basically, “device not working…replace device.” Patients were candidates for primary VAD implantation and potentially previous exchange(s) and typically are for future exchange. In addition, patients’ previous histories with VADs provide some guidance as to anticipated post-VAD exchange courses.
Perhaps the most important questions regarding VAD exchange relate to surgical technique, which may vary substantially between individual cases. What incision(s) should be used? Should extracorporeal circulation be used, and if so, via what cannulation strategy? What exactly ought to be replaced, and how?
The greatest familiarity with VAD exchange is with the Heartmate 2 device. While the need for VAD exchange is clearly the highest,4 in comparison to the Heartware HVAD and Heartmate 3 devices, VAD replacement typically is straightforward. This is because the Heartmate 2 is modular, and when appropriate (e.g., in the absence of device infection, or inflow cannula or outflow graft disorders), the pump mechanism can be changed without work required on the inflow cannula/LV inflow sewing ring or the outflow graft.5 Pump mechanism exchange can be accomplished via a left subcostal incision rather than reoperative sternotomy.5 In contrast, HVAD and Heartmate 3 VAD exchange require dissection to the LV inflow sewing ring, because disengaging the pump mechanism is required; also, a minimum of a new-to-old outflow graft-outflow graft anastomosis is required. Consequently, reoperative sternotomy is typically used, but alternative approaches exist.6 For all device changes, cardiopulmonary bypass is most commonly employed. However, “off-pump” tactics have been reported.7
With respect to outcomes, although perioperative results are satisfactory, 1 year mortality may be substantial. Two studies of Heartmate 2 exchanges,8,9 the latter of which examined exchanges to the Heartware device, independently reported 1 year mortalities of ≈30%. Although device exchange typically does not require an extensive preoperative evaluation and may be performed without an extended waiting time, these results prompt discussion and consideration of other options.
Option 2: Device Explantation
Although pump exchange is the de facto treatment for most patients with VAD failure, it exposes them to the ever-present long-term risks of durable VADs, in addition to reoperative risk. This may be a hazardous proposition, particularly for patients who have sustained complications of VAD therapy. Additionally, not everyone is a candidate for HT, which also entails an unpredictable waiting period. Consequently, device explantation may be the most appropriate strategy to deal with VAD failure in some patients. For these patients, VAD explant may provide survival, freedom from VAD-related complications, and quality of life.
Durable LV functional recovery after a period of LVAD support occurs in a subset of LVAD-supported patients with idiopathic cardiomyopathies without underlying structural or coronary arterial disease. This has been associated with reversal of the neurohormonal derangements characteristic of and contributory to the pathogenesis of HF.10 However, a key and poorly resolved issue is estimation of the achievement and durability of myocardial recovery or at least remission from advanced HF. The ability to explant a VAD based upon preexplant assessment does not necessarily translate to long-term LV myocardial recovery.11 In some cases, LVAD-supported hearts exhibit improved myocardial function and reverse remodeling transiently, such that deterioration of LV function occurs over time postdevice explant.10 We do not have reliable clinical or pathophysiologically appropriate animal models to study myocardial recovery, but recent work has identified signatures of a “point of no return.” One study identified disruption of the T-tubule system in cardiomyocytes as an ultrastructural feature associated with failure to achieve LV reverse remodeling with mechanical unloading.12 As the accompanying editorial highlights, this ultrastructural feature not only was a signature of the truly end-stage myocardium, but perhaps expectedly, this correlated with the duration of HF antecedent to LVAD implantation.13 Thus, in patients with LVAD failure and evidence of LV functional recovery and reverse remodeling, we need to cautiously consider VAD explantation as a strategy, thereby avoiding pump exchanges or HT.
Option 3: Heart Transplantation
HT is the gold-standard treatment for ESHF, with better survival compared with CF LVAD implantation.14,15 However, HT often is not feasible up front, necessitating initial CF LVAD implantation. Yet, VAD failure occurs and requires treatment, and bridge-to-HT in the setting of VAD failure is a treatment option to consider. As discussed, device exchanges are associated with increasing mortality as a function of number of exchanges (1 year survival: first pump replacement 64%; second pump replacement 50%).16 For patients with persistent ESHF, HT offers definitive and superior treatment to device exchange, with superior outcomes. However, many CF LVAD recipients are not HT candidates or cannot receive HT in a timely fashion. With respect to the latter of these, the previous 3 tier US donor heart allocation system did not adequately risk-stratify patients with ESHF based on urgency and did not adequately incorporate the negative impact of CF LVAD-related complications. However, the new allocation system, in effect since late 2018, stratifies patient risk into 6 tiers, largely based on a combination of the severity of cardiac failure (risk of impending mortality in the absence of HT) and ascertained survival benefit achieved with HT. In the current scheme, CF LVAD complications—and overt VAD failure in particular—are highly prioritized (Table 1). Thus, the a priori probability that VAD failure may be treatable via HT now has increased. Future analyses will determine if the changes to the donor heart allocation system are favorable to patients with VAD failure. However, based upon studies such as Chou et al.2 with respect to VAD exchange outcomes, for CF LVAD recipients with VAD failure who are candidates for HT and can wait for a period of time, HT likely offers the best outcomes.
VAD failure exerts an important negative impact upon CF LVAD recipients. Improved device components, operative techniques, and postoperative management are essential to achieving the best possible outcomes. However, when VAD failure occurs, identifying and choosing the most appropriate strategy is critically important (Figure 1). To exchange, explant, or transplant; that is the question.
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