Considering the outcome after VAD implantation in this cohort, five patients were transplanted, six patients died on device because of non AI-related causes, and one patient underwent device inactivation and ligation of the outflow graft after partial recovery of the left ventricle. There were no statistically significant differences in the survival rate between patients who developed AI during the follow-up and patients without AI (p = 0.575).
In this study, we present our experience with the prevalence of AI in patients supported with HeartWare LVAD. To our knowledge, this is the first study evaluating specifically the incidence of de novo AI in patients supported with HeartWare LVAD. The main finding of the study is that the incidence of > mild AI appears to be very rare in patients supported with HeartWare LVAD. In this study, after median VAD support duration of 408 days (77–1250 days), eight patients had trace/mild AI (24%) and merely one patient developed moderate AI (3%). None of the patients developed severe AI and/or required surgical or other procedural intervention of AI.
The mechanism involved in VAD-induced AI is multifactorial and related to variations in blood flow and pressure in the aortic root.8 A high velocity in the ascending aorta because of mismatch in the LVAD outflow graft diameter and ascending aorta may potentially cause aortic root weakening, dilation, and AV cusp malcoaptation.9 Furthermore, high-pressure and velocity jets of regurgitant blood volumes contacting the root side of closed AV may result in valvular damage and degeneration. Another contributing mechanism in the development of AI in LVAD patients include changes to the aortic wall because of sheer stress and high diastolic luminal pressures.10 Once AI is developed in a patient with LVAD, it is clear that valvular incompetence decreases pump efficiency and can lead to worsening heart failure. The immediate consequence of any degree AI is the creation of a redundant circulatory loop whereby retrograde blood flow is returned to the left ventricle through the incompetent valve.11
During the last few years, many studies reported on the issues of developing AI in patients supported with continuous-flow LVAD.4–8,10,12,13 Almost all of these studies involved patients supported with HeartMate II.4,6,10 Cowger et al.10 reported a relatively high incidence of AI in a cohort comprising 53 patients with HeartMate II having freedom from moderate and greater AI of 86, 72, and 36%, at 6, 12, and 18 months, respectively. Pak et al.12 from Columbia University analyzed 63 HeartMate II patients and reported freedom from more than mild AI of 83.6% at 6 months and 75.2% at 12 months. The authors concluded that AI occurs frequently in patients who receive continuous-flow support with a HeartMate II and may be associated with aortic root diameter enlargement and AV opening. Jorde et al.4 recently published a comprehensive study from the same institution involving 232 patients (223 HeartMate II und 9 HeartWare patients). In that study freedom from greater than mild de novo AI at 1 year was 78%. However, at least moderate AI was seen in 38% of the patients after 3 years. Therefore, the authors concluded that AI is common in continuous-flow LVAD patients and may lead to clinical deterioration and surgical intervention. Notably, the prevalence of AI was substantially lower in patients whose AV opens. In a similar study from Aggarwal et al.6 involving 79 patients with HeartMate II, a significant AI (mild or greater) was seen in 52% of patients after a median support duration of 761 days. A higher incidence of AI was seen in patients with closed AVs and older age group. Meanwhile, Rajagopal et al.13 described their experience with 148 continuous-flow LVAD patients comprising 139 HeartMate-II, 6 HeartWare LVAD, and 3 VentrAssist devices (Ventracor, Sydney, New South Wales, Australia), with freedom from moderate or greater AI at 1 and 2 years being approximately 50% and 30%, respectively. In another study from Patil et al.7 involving 58 HeartMate II and 35 HeartWare patients, overall freedom from moderate or greater AI was 94.7% at 1 year, 86.9% at 2 years, 82.8% at 3 years, and 31% at 4 years. The most important independent risk factors for of AI development in that study were the duration of support and persistently closed AV.
The aforementioned studies have several points in common: first, a substantial proportion of patients with HeartMate II develop at least moderate AI during the follow-up, and second, the most important risk factor for AI development is the persistently closed AV and longer support duration. In contrast, the finding of our study, which involves only HeartWare patients, does not support these results. Notably, the clinical relevance of AI development in the majority of HeartMate II patients seems to be negligible as these patients are rarely urgently transplanted only because of AI and/or require AV replacement.
Possible Explanations of Lower De Novo AI in HeartWare Patients
There are several explanations of observing only few, clinically not relevant, de novo AI in this cohort of patients. We assume that the activation of the lavare cycle, which involves periodic variation in the pump speed every 60 seconds that allow opening of the AV (Figure 1), is one of the potential reasons beyond having a significantly less de novo AI in our cohort. We observed only eight patients with trace/mild AI (24%) and one patient with moderate AI (3%) after a median VAD support duration of 408 days (77–1250 days) (Figure 2). This AI rate is significantly less than the reported AI incidence in previously reported studies, which mainly involve HeartMate II patients.4,6,10 As lavare cycle may cause intermittent opening of the AV and several studies report persistently closed AV as a risk factor for AI development, it is intuitive to speculate that the activation of lavare cycle may be one of the possible explanations of low AI incidence in this study cohort.
Another possible explanation of having low de novo AI rate in this cohort may be related to postoperative patient management. During the follow-up, an average pump flow, index, and speed of 4.4 ± 0.6 L/min, 2.3 ± 0.4 L/min/m2, and 2585 ± 147 rpm were documented, respectively. We did not see any statistical significant difference between these parameters in patients with no AI versus patients with trace/mild AI (Figure 5, B–D). However, there was a trend toward having higher pump speed and pump index in patients who develop clinically irrelevant trace/mild AI (p = 0.17 and 0.17, respectively).
Further explanation of the low AI rate in this cohort may be related to strict blood pressure monitoring protocols at our institution. All of our patients are advised before discharge to measure the blood pressure daily and keep their MAP below 85 mm Hg. The patients are all supported with blood pressure measurement device (Doppler sonography or digital sphygmomanometer in the presence of arterial pulsatility) shortly after hospital discharge. It is somewhat intuitive to expect higher AI rate in patients with continuously high blood pressure. The average documented MAP in this cohort was 88 ± 11 mmHg. However, no statistically relevant difference was detected in the MAP between patients with or without trace/mild AI (Figure 4A).
Another potential explanation of having less AI in this cohort may be related to opening status of the AV. The negative impact of closed AV on the development of de novo AI in LVAD patients has been previously reported.4,6,7 Therefore, some investigators have proposed to facilitate AV opening actively by running the pump at lower speeds.14 In this study, 22 patients had continuously open AVs, 8 patients had intermittent AV opening and 4 patients had persistently closed AV. Figure 3 shows the relationship between the severity of AI and AV opening status. Similar to the results of the aforementioned studies, AI graded as trace/mild was more frequently encountered in those with intermittently closed AV.
Comparing HeartWare LVAD with HeartMate II
Both HeartWare LVAD and HeartMate II pump are considered as new-generation continuous flow pumps. However, the pump design is completely different. HeartWare is a centrifugal pump, and HeartMate II is an axial pump. The current study was not designed for a rigorous head-to-head comparison of HeartMate II versus HeartWare but does afford an insight into the perspective of postimplantation AI in patients supported with HeartWare LVAD. We observed a significantly lower rate of moderate AI development in this study compared with previous studies with HeartMate II.4,6,10 The limited number of patients supported with HeartMate II at our institution precludes comparing these two pumps with regard to AI development in this study. Patil et al.7 reported in a different study a higher incidence of AI in patients with HeartWare LVAD compared with HeartMate II. However, that study was retrospective in nature and was not a propensity-matched study, and the HeartWare patients in that study were older and comprised more patients with diabetes mellitus. Interestingly, the lavare cycle was deactivated in all of these patients (personal communication with Harefield physicians), which may also explain the higher incidence of de novo AI in that study compared with our study.
Limitation of the study includes the limited number of subjects included in this study. On the basis of our data, we can only assume that lavare cycle may explain the lower AI incidence in HeartWare patients. This finding can only be confirmed if these patients are compared with another cohort of HeartWare LVAD patients without activated lavare cycle. This comparison was not feasible in this study as we activate lavare cycle in every HeartWare LVAD patient. Another limitation includes a relatively short follow-up time in our cohort. The median VAD support duration in this study was 408 days (77–1250 days). The number of patients on support after 1 year was few, and more studies are necessary to examine the incidence of de novo AI in patients with HeartWare ventricular assist device and longer durations of support. However, on the basis of the results of the previously reported studies with HeartMate II,4,6,10 we should have seen a much higher moderate AI rate even after this support duration. Another limitation includes the absence of preoperative aortic root diameter measurements in these patients and its correlation with AI development. Finally, no data exist regarding the changes in the right ventricular function and its correlation with AI development in these patients.
It appears that some HeartWare patients develop clinically irrelevant trace/mild AI during the follow-up. However, the development of > mild AI seems to be rare in these patients. The development of trace/mild AI was more frequent in patients with intermittently closed AV during the follow-up. The opening of AV is frequent in HeartWare patients, and this may also explain the low AI development. Further prospective studies are necessary to confirm this finding.
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de novo aortic valve insufficiency; aortic regurgitation; circulatory support devices; cardiomyopathy; adult; heart failureCopyright © 2016 by the American Society for Artificial Internal Organs