**3.2 Management of Valvular Disease**

Valve surgery at the time of LVAD implant is common and uniformly increases morbidity relative to LVAD surgery alone. Mortality data with valve surgery at the time of LVAD are mixed. In the HMII trials, 21.9% underwent valve surgery with modestly increased mortality (1-year survival: 69% vs. 75%, p = 0.004) [90]. In the ADVANCE trial, 19.6% had concomitant valve surgery, and though the absolute difference in survival was the same as with HMII, the result was not significant (79% vs. 85%, p = 0.33) [91]. In the MOMENTUM 3 CAP registry, 21.8% had valve surgery with equivalent survival at 2-years (81.7% vs. 80.8%, p = 0.6) [92]. Registry data show a similar prevalence of valve surgery at LVAD implant (IMACS, 12.1%; [30] EUROMACS, 19.3% [93]). When those having valve surgery in EUROMACS were propensity matched to LVAD patients not undergoing valve surgery, 1-year survival was the same (67.9% vs. 66.4%, p = 0.25) [93].

Notably, early right HF was actually higher with concurrent valve surgery in the HMII [90], ADVANCE [91], and HM 3 trials [92], while the propensity matched cohort in EUROMACS had equivalent rates of RVAD use [93]. Late right HF was not different in the HMII or ADVANCE trials but was increased with concurrent valve surgery in the MOMENTUM 3 CAP registry.

#### *3.2.1 Aortic valve disease*

Hemodynamically significant AI can be addressed via 3 methods (reviewed in detail elsewhere) [94]: (1) complete closure (oversewing) of the AV; (2) AV repair (e.g., central closure via Park's stitch [95]); or (3) AV replacement (AVR). Closure successfully eliminates AI, but acute LVAD malfunction may be rapidly fatal as this method leaves no native cardiac output. AV repair closes the central orifice of the AV while still allowing blood flow through the lateral commissures. This prevents blood stasis and thrombosis in the aortic root, and durably limits AI [94]. Of note, if AVR is pursued, mechanical valves are not recommended due to decreased valve opening and blood flow that could increase the chance of thrombosis.

Outcomes data distinguishing the best approach are extremely limited. Among those with concurrent AV and continuous flow LVAD surgery between 2006 and 2012 in INTERMACS, survival was lower with AV closure than either AV repair or AVR, suggesting that preservation of AV opening is beneficial [96]. More recent data from IMACS showed reduced survival with concurrent procedures, with AV repair having numerically better survival than AVR [70]. However, data were compared to no AV surgery, leaving unclear if the difference between repair and AVR was significant. In both studies, CPB time and LOS were longer with AV procedures.

Though mortality may be increased, residual confounding is possible due to the lack of prospective, randomized data. Whether AV procedures are of benefit in a subpopulation of LVAD patients remains unclear. Among concomitant AV procedures in IMACS, ~50% were performed in those with mild AI [70]. Interestingly, when this analysis was limited to those with moderate or severe AI, survival was the same between AV repair, AVR and those not receiving AV surgery. This suggests that the benefit may be restricted to those with more severe disease.

Finally, as noted, AI will develop and/or progress in the majority of LVAD patients (**Figure 8B**). Despite this, data on the optimal approach to these patients is markedly limited. Post-LVAD AI has been managed with (1) open AVR; (2) percutaneous closure of the aortic valve with an occlusion device (e.g., those used for septal defects); or (3) percutaneous AVR (TAVR). Percutaneous methods have increased over the last decade but no large-scale studies have been performed to study different approaches. In a meta-analysis of 15 case series (only 29 patients), percutaneous treatments were durable and showed no difference in mortality between occlusion or TAVR [97]. A study using the Nationwide Readmission Database found no difference in mortality between surgical AVR and TAVR but showed substantially lower morbidity with TAVR [98]. Given the prevalence of post-LVAD AI, this is an urgent area for future research.

### *3.2.2 Mitral valve disease*

Intraoperative management of moderate or severe MR remains controversial. Among those with moderate or severe MR in INTERMACS, only 5.3% underwent MV surgery (95.8% repair, 4.2% replacement) at the time of LVAD [99]. MR severity 3-months after LVAD was equivalent in both groups (moderate/severe MR in 20% with MV procedure, 25% with LVAD alone, p = 0.2). Importantly, there was no survival benefit between: (1) those with moderate/severe MR undergoing LVAD and MV surgery vs. LVAD alone; (2) those with baseline moderate vs. severe MR; nor (3) those with baseline no/mild MR vs. moderate/severe. A trend (p = 0.09) towards benefit of concurrent MR surgery 2-years after LVAD was noted in DT patients. MV

surgery was associated with longer LOS and CPB time, but fewer rehospitalizations. The incidence of right HF was the same and 6-minute walk distance was not different with or without concurrent MV surgery [99].

These data suggest there is little benefit to correcting MR at the time of LVAD and risk predictors have not been established to identify subgroups who might derive benefit. However, in INTERMACS, the presence of moderate or severe MR at least 3-months after LVAD implant was associated with a nearly 2-fold increased risk of right HF and a trend towards lower survival [75]. Data are lacking to guide management in LVAD patients with significant residual MR.

### *3.2.3 Tricuspid valve disease*

Surgical treatment of moderate or severe TR at the time of LVAD is similarly controversial. Among those with moderate/severe TR in INTERMACS, 16.5% underwent TV surgery (>95% repair) at the time of LVAD [100]. TV surgery was associated with slightly lower survival (hazard ratio 1.13, p = 0.04) and significantly higher rates of stroke, bleeding and arrhythmia. Concurrent TV surgery did not impact patientreported QOL [100]. In a propensity matched cohort from EUROMACS, TV surgery had no impact on survival, readmission, or right HF after LVAD [101]. Further, at 1-year, the prevalence of moderate or severe TR was similar between those with TV surgery or LVAD alone [101]. Other large single center studies have confirmed a high failure rate (~30–40%) of TV surgery in LVAD patients [102, 103]. Notably, the rate of concurrent TV surgery has declined in the last decade, possibly in response to the mounting evidence for a lack of benefit. Whether subgroups that do benefit can be identified remains to be determined.

#### **3.3 Management of LVAD device malfunction**

While failure of any part of the LVAD can be life threatening, the majority of issues with external components are readily remedied without harm [79]. By contrast, LVAD thrombosis almost always requires therapy (**Figure 9**). Pump or driveline failure triggering LVAD exchange occurred in 0.6% of HMII recipients in an early INTERMACS analysis [104]. Driveline malfunction (more common with the HMII than HVAD) rarely requires urgent intervention. Major driveline issues occurred in ~2.2% of >13,000 HMII patients, and of those only 20% required urgent surgical intervention (driveline repair, pump exchange, OHT) [105]. There are as yet no data on the incidence and outcomes of driveline issues with the HM3.

Lastly, LVAD cannula problems should also be considered in the differential diagnosis of recurrent HF. Although rare, malalignment of the inflow cannula may require surgical correction. Outflow cannula obstruction is predominantly caused by external compression of the outflow graft or stenosis of the aortic anastomosis [83]. While surgical correction is an option, the safety and long-term durability of outflow graft stenting has recently been confirmed and can be performed with very low morbidity [83].
