The principal findings of this analysis were: 1) that early post-LVAD VA is common even in the contemporary continuous flow LVAD era (38%), while late post-LVAD VA occurred in 55% during long term follow-up; 2) pre-LVAD VA but not early post-LVAD VA was an independent risk factor for late post-LVAD; and 3) early post-LVAD VA was associated with a higher mortality in the DT population.
Early VAs after LVAD implantation are common with a reported incidence between 13% and 25% in patients with continuous flow LVADs (3–6). Our study reports a higher incidence of early VAs (37%). This may be driven by variation in the definition of early VAs, with some studies using the first week rather than the first 30 days after LVAD implantation (7). This difference may also be explained by the high percentage of patients in our cohort with a history of VAs prior to LVAD (51%) relative to other studies using the same definition, suggesting a higher risk population. This reflects practice patterns prior to the UNOS allocation system change (Oct 18, 2018) where patients with refractory VAs and low ejection fraction were likely to receive LVADs as a BTT given the long wait times in UNOS Region 7.
Pre-LVAD VT was an independent predictor of both early and late post-LVAD VA. Pre-LVAD VA has been described as a predictor of post LVAD VA in general (6, 8), early and late post-LVAD VA in particular (3–5, 9). This suggests that pre-existing substrate may be a large driver for ventricular arrhythmias in patients after LVAD. Indeed, multiple studies reported that the majority of ventricular arrhythmias ablated in the LVAD population are related to scar remote form the LVAD canula. (10–13). While pre-LVAD was an independent predictor of late post LVAD VA, early post LVAD VA was not after adjusting for pre-LVAD VA. This result is different that the findings by Galand et al. where early post LVAD VAs were still an independent risk factor for late post LVAD VAs (9). This difference is probably due to the fact that our population is higher risk with more pre-LVAD VAs (33.4% versus 51.3%) and more substrate to drive post LVAD VAs. Many patients without pre-existing VAs, however, develop VAs after LVAD suggesting that there are still mechanisms that are specific to early post LVAD VAs including electrolyte abnormalities, suction events, inotropic agent use, perioperative ischemia and acute right ventricular dysfunction and LVAD cannula associated scar (4, 7, 14, 15).
The association of early post LVAD VA and mortality we observed in the DT cohort is consistent with other observational studies that have also demonstrated an increased mortality with VAs, particularly early post-LVAD VAs (4, 5, 16–19). A recent meta-analysis of 9 observational studies including 1,179 patients also revealed an association between post-LVAD VAs and mortality (20). However, this association is not consistent (21). A recent analysis of data from the INTERMACS registry showed no such association (22). It is known that INTERMACS reporting is often incomplete, which limits the strength of the conclusions drawn with using this data. This highlights the importance of high-quality data to answer clinically relevant questions in the LVAD population. Given the event rate in this population, a large sample size is often not needed to have confidence around a result.
In our study, early post LVAD VA was independently associated with mortality in the DT population, but not in the overall cohort or the BTT population. In the DT population, this increase in morality occurred immediately after LVAD implantation and the separation in survival curves persisted until the end of follow up. There was not a statistically significant increase in mortality in the BTT VAD recipients who developed early post-operative ventricular arrhythmias, however there was a trend in that direction with a log rank p value of 0.07. One possible explanation for the lack of separation in survival curves in the BTT cohort is the potential for early transplantation, however the practice at the University of Minnesota is to wait at least 3 months before re-listing BTT patients after surgery. One potential mechanism for the association between early post LVAD VAs and 30-day mortality is that VAs can lead to worsening right ventricular failure in the high risk post-operative period (3). It may be that the BTT population, who have less co-morbidities, have more reserve to handle this early complication and the potential treatments that accompany it such as ablation therapy, repeated cardioversions, RVAD support and/or antiarrhythmic therapies.
This study is an observational, single center, nonrandomized study. However, most of the findings agree with previously published data from other centers and it has a relatively large sample size with high quality, complete data and includes the most contemporary pumps. This study design cannot determine whether VAs are the cause of the increase in mortality observed, hence does not shed light on whether treating the VAs aggressively would improve survival in this patient population. And finally, the mortality analysis for early new onset post LVAD VAs may be underpowered to show a significant result.