*2.2.1 Aortic regurgitation*

Significant aortic valve insufficiency (AI) can create a short circulation loop in LVAD patients whereby a substantial fraction of the blood pumped by the LVAD to the aorta returns directly to the LV (**Figure 7**). This reduces effective perfusion, causes LV distention and elevates left heart filling pressures, ultimately causing HF. Consequently, moderate to severe AI is a contraindication to LVAD unless valve intervention is planned at the time of surgery [68].

Among patients in the STS-INTERMACS database implanted between 2016 and 2020, only 0.7% had severe AI at the time of LVAD surgery [8]. Moderate or severe AI was present at implant in 4.5% of over 16,000 patients in the IMACS database [30]. By contrast, mild AI prior to LVAD is relatively common, being found in 29.7% of patients in INTERMACS [69] and 31.2% in IMACS [70].

#### **Figure 7.**

*Aortic valve insufficiency (AI) with an LVAD. Significant AI creates a short circulation loop whereby a substantial portion of LVAD flow regurgitates back into the LV. This reduces functional cardiac output and increases left heart filling pressures, ultimately causing heart failure.*

#### *Recurrent Heart Failure after Left Ventricular Assist Device Placement DOI: http://dx.doi.org/10.5772/intechopen.107022*

Importantly, AI can progress or develop de novo after LVAD implant; this is clearly a result of LVAD support rather than disease progression (**Figure 8A**) [71]. Two mechanisms drive the development of AI on LVAD support. First, full LVAD support substantially reduces or completely eliminates aortic valve (AV) opening during systole. This promotes fusion of the commissures between valve leaflets; the resulting fibrosis causes retraction of the leaflets and AI with a central regurgitant jet. Second, decompression of the LV and the high volume delivered to the proximal ascending aorta generates a substantial and continuous pressure gradient across the valve that favors flow into the LV.

The prevalence of AI increases with the duration of LVAD support (**Figure 8B**); in INTERMACS, 13.2% developed moderate/severe AI over a mean follow-up of 13.4 months [69]. Of those with no AI prior to LVAD, 10.7% developed moderate or severe AI, while 18.9% with mild AI prior to LVAD developed moderate or severe AI. By 6-months post-LVAD, 55% had developed at least mild AI.

Key factors that increase the risk of significant AI across multiple studies are (1) older age at LVAD implant; (2) female sex; (3) low body surface area; (4) longer duration of LVAD support; (5) baseline mild (vs. no) AI; (6) no AV opening; and (7) continuous flow (vs. pulsatile) pump [69, 71–73]. The presence of moderate or severe AI is associated with a modest but significant increase in hospitalizations [69]. Moderate/severe AI is also associated with greater severity of MR, but surprisingly, is not associated with significantly worse QOL or reduced 6-minute walk distance. Finally, the presence of moderate or severe AI (vs. no or mild AI) is associated with lower survival (49.1% vs. 35.6% at 5-years, p < 0.001) [69].

#### *2.2.2 Mitral regurgitation*

Hemodynamically significant mitral regurgitation (MR) is the commonest valve lesion at the time of LVAD implant. It is almost always functional MR secondary to LV dilation. Among >26,000 patients in STS-INTERMACS, 22.8% had severe MR

#### **Figure 8.**

*Natural history of aortic insufficiency (AI) after LVAD implant. (A) Proportion of patients with progression of AI from baseline up to 4-years in those receiving an LVAD as compared to patients with end-stage HF who did not undergo LVAD surgery (NS-ESHF). Reprinted with permission [71]. (B) Progression and severity of AI in LVAD patients from the INTERMACS database, with number of patients assessed listed above each bar. Reprinted with permission [69].*

at baseline [8]. Similarly, at implant, 57% had moderate/severe MR in IMACS [30], and 46% had moderate/severe MR, or underwent concomitant MV surgery in the MOMENTUM 3 trial [74].

With offloading of the LV, MR improves in the majority of LVAD patients [74]. When moderate to severe MR persists, the impact on outcomes remains uncertain. In the MOMENTUM 3 trial, persistent MR was uncommon (~6.5% at 1-year, n = 619), and was not associated with survival, adverse events including right HF, or functional capacity [74]. However, in INTERMACS (n = 8364), persistent MR was ~3-fold more common (18.8% at a median of 15 months), and was associated with increased rates of right HF and renal failure, and a modest 16% increase in mortality of borderline significance (p = 0.07) [75]. Single center studies also show mixed results, with frequent right HF but little to no impact on survival.

#### *2.2.3 Tricuspid regurgitation*

TR is also common in advanced HF. In the STS-INTERMACS database, 11.5% had severe TR at baseline [8], and 41% had moderate or severe TR at implant in the IMACS database [30]. Improvements in PVR and afterload with LVAD support often leads to a reduction in TR [23, 76]. Outcomes data on post-LVAD TR are very limited, but large single center studies as well as data from the EUROMACS registry suggest that moderate or severe TR after LVAD is associated with a small but significant increase in mortality [76, 77].

#### **2.3 Device malfunction**

Right HF can be caused by device malfunction, cannula obstruction or inappropriate LVAD speed. LVAD pump thrombosis is discussed elsewhere in this textbook. Data on device malfunction and outcomes are scant. Further, malfunction caused by manufacturing problems often leads to a recall, which abruptly changes incidence [78]. LVAD failure as a cause of death occurs in ~2% [8, 30], with events declining in recent years [8]. In a large single-center study, device malfunction occurred at a rate of 3.06 events per 1000 patient-days [79]. Notably, device malfunction is pumptype specific, with more events in the HMII. The only data for the HM3 comes from the European ELEVATE registry, which showed device malfunction in 3.9% [80]. However, almost 90% of these events were due to outflow graft twisting, a problem since corrected by the manufacturer.

Device malfunction can be grouped by the component that failed: (1) controller; (2) pump/driveline; and (3) peripheral components (e.g., cables, batteries, monitor). Importantly, not all malfunction results in right HF, with pump or driveline failure the most likely to result in a clinically significant event (i.e., HF or death). Controller malfunction was commonest (~30%), while pump or driveline malfunction constituted 13% of malfunction events [79].

Inflow cannula obstruction is a rare event, typically associated with thrombus and/or cannula malposition [81]. Abnormal inflow cannula position is associated with increased left heart filling pressures and a > 2-fold increased risk of recurrent HF [82]. By contrast, outflow cannula obstruction is more common and likely underappreciated; dozens of case reports and case series exist, with an event rate of 0.03 EPPY in the largest study [83]. The commonest pathology seems to be external compression from buildup of an acellular fibrinous material between the outflow graft and the protective GoreTex wrap that is frequently placed around the graft at implant. Notably, ~80% of patients with clinically significant outflow cannula obstruction will have recurrent HF [83].
