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Clinical Cardiovascular

Moderate Aortic Insufficiency with a Left Ventricular Assist Device Portends a Worse Long-Term Survival

Auvil, Bryan; Chung, Jennifer; Ameer, Alyse; Han, Jason; Helmers, Mark; Birati, Edo; Acker, Michael; Atluri, Pavan

Author Information
doi: 10.1097/MAT.0000000000001071
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Abstract

New development or worsening of aortic insufficiency (AI) is a well-known complication of mechanical circulatory support with left ventricular assist devices (LVAD).1–10 Different series have reported incidence of new, significant, or worsened AI between 15% and 52% by 1 year.1,9 Two of the biggest risk factors identified thus far are age and duration of LVAD support, with patients on longer-term therapy more likely to develop AI.4,10 Other risk factors have been identified, including postoperative aortic valve (AV) opening, functional mitral regurgitation, female gender, and destination therapy designation.4,10 The pathophysiology is thought to be due to altered flow dynamics and reduced valve opening, which lead to both commissural fusion and increased aortic root pressure that results in annular dilatation.8,11,12 Pre-existing, hemodynamically significant AI (often defined as ≥moderate AI) is known to adversely affect outcomes and is typically treated at the time of device implant with valve repair, replacement, or closure.13–15 The literature is less clear, however, on the importance of AI that worsens or develops de novo during the course of LVAD support. Some studies have demonstrated worse functional status, higher readmission rates, and worse survival in patients with moderate or greater AI,10,16 while other studies have failed to detect a difference in mortality.1,4,6 Furthermore, the amount of long-term data is limited, with most studies not reporting follow-up past 1–2 years.

As VAD technology continues to improve, and more and more patients are placed on destination therapy, it becomes increasingly important to determine the significance of AI as a means of maximizing survival of this complex patient cohort. Moreover, this might guide earlier treatment or intervention in these patients to further improve outcomes. We hypothesized that moderate asymptomatic AI would have an adverse impact on long-term survival. Therefore, we undertook this study to determine the effect of moderate asymptomatic AI on survival. A secondary analysis of the impact on shorter term functional exercise capacity and right ventricle function was carried forth. Earlier treatment or intervention in these patients, as well as improved management of pump settings meant to delay or prevent AI development may be warranted.

Materials and Methods

We performed a retrospective review of patients who received a HeartMate II or HeartWare (LVAD) at our institution between 2008 and 2018. Patients with LVAD support of less than 6 months and those who underwent concomitant AV procedures during implant were excluded. Two-hundred twenty-one patients were identified and were stratified by AI severity at 6 months (none-0, mild-1, and moderate-2). One hundred eleven, 92, and 18 had no, mild, and moderate AI, respectively, at 6 months. No patients had severe-3 AI at 6 months. Patients were censored from the study after undergoing cardiac transplantation. Patient baseline characteristics and follow-up data were collected from our institution’s Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database, with Institutional Review Board approval.

Outcomes

The primary outcome analyzed was 2 year survival. Secondary outcomes included: (1) 6 minute walk distance at 1 year and (2) right heart failure at 1 year. Right heart failure was defined per INTERMACS criteria as both: (1) central venous pressure or right atrial pressure >16 mm Hg by right heart catheterization or significantly dilated inferior vena cava with the absence of inspiratory variation by echocardiography or clinical finding of jugular venous distention at least halfway up neck in an upright patient and (2) clinical finding of peripheral edema—2+, new or unresolved or the presence of ascites or palpable hepatomegaly on physical examination or by diagnostic imaging or laboratory evidence of worsening hepatic (total bilirubin > 2.0 mg/dl) or renal dysfunction (creatinine >2.0 mg/dl).

Statistical Analysis

All analyses were performed using STATA statistical software (StataCorp., College Station, TX). A 2 sided significance level of 0.05 was used for all statistical testing. One-way analysis of variance (ANOVA) was used for between-group comparisons. Multivariable logistic regression (mortality, right heart failure) and multivariable linear regression (6 minute walk) analyses were used to estimate the effect of baseline characteristics on primary and secondary outcomes. Survival based on AI status was estimated by Kaplan-Meier methods.

Results

Two-hundred twenty-one total patients were identified, with a median follow-up time of 547 days. The median cohort age was 57, with 86% male. One hundred twenty-two (55%) patients received LVAD for destination therapy. Median follow-up time was 497, 554, 537 days in the none, mild, and moderate groups, respectively, with 92 (42%) total patients remaining at 2 years. Twenty-four (22%), 15 (16%), and three (17%) patients were censored for transplant over the 2 year study period in the no, mild, and moderate AI groups, at an average of 310 (±130) days from LVAD implantation.

At the time of LVAD implantation, 10 patients had moderate AI, and 89 patients had mild AI. Of the 122 patients with no pre-existing AI at LVAD implant, 44 (36%) and five (4%) progressed to mild and moderate AI at 6 months, respectively. Of the 89 patients with mild pre-existing AI, 10 (11%) progressed to moderate AI.

Eleven patients underwent concomitant AV surgery at the time of LVAD implantation and were excluded from the main analysis. Of these 11 patients, one developed mild AI, and one developed moderate AI by 6 months. Both patients with recurrent AI had received AV closure with Park’s stitch during implant. Two patients died during the study period, both of whom had no recurrent AI at 6 months. These patients had both received AV replacement, one biological and one mechanical.

Patient baseline characteristics by group are listed in Table 1. Patients with moderate AI at 6 months were older (P = 0.0061), had higher rates of preimplant AI (P = 0.0026), mitral regurgitation (P = 0.0035), and coexisting pulmonary disease (P = 0.005), and were more likely to receive LVAD for destination therapy (P = 0.0262).

Table 1. - Patient Baseline Characteristics and Primary/Secondary Outcomes (Mean ± SD or n [%])
AI at 6 Months 0 (None)
n = 111
1 (Mild)
n = 92
2 (Moderate)
n = 18
p
Baseline characteristics
Age 52.1 ± 14.9 57.8 ± 12.9 59.8 ± 12.2 0.0061
Male sex 90 (81.7%) 86 (93.2%) 14 (77.8%) 0.0384
BMI 29.6 ± 7.2 29.2 ± 6.8 25.7 ± 4.9 0.0882
Cardiac output (L/min) 4.5 ± 1.4 4.2 ± 1.7 3.9 ± 1.1 0.1780
Pump speed (HeartMate II) 9,140 ± 820 8,730 ± 1,330 9,590 ± 504 0.010
Pump speed (HeartWare HVAD) 2,720 ± 215 2,780 ± 180 3,031 ± 404 0.054
Chronic kidney disease 33 (29.7%) 36 (39.1%) 6 (33.3%) 0.3738
Lung disease 11 (9.9%) 15 (16.3%) 7 (38.9%) 0.0050
Creatinine 1.48 ± 0.96 1.42 ± 0.47 1.53 ± 0.68 0.7931
CPB time 75.7 ± 42.1 82.2 ± 38.4 86.0 ± 33.7 0.4073
Prior cardiac surgery 41 (36.9%) 26 (28.3%) 5 (27.8%) 0.3845
Preimplant MR 1.6 ± 0.8 1.8 ± 0.9 2.4 ± 0.8 0.0035
Preimplant AI 0.4 ± 0.6 0.5 ± 0.5 0.9 ± 0.7 0.0026
Destination therapy 55 (49.5%) 52 (56.5%) 15 (83.3%) 0.0262
Results
2 year mortality 12 (10.8%) 8 (8.7%) 8 (44.4%) 0.0001
6 minute walk distance at 1 year 1,301 ± 322 ft. 1,155 ± 407 ft. 973 ± 459 ft. 0.1421
Right heart failure at 1 year 20 (25.6%) 27 (38.6%) 5 (38.5%) 0.2189
Groups were compared by one-way analysis of variance.
AI, aortic insufficiency; CPB, cardiopulmonary bypass; MR, mitral regurgitation; SD, standard abbreviation.
Bold values represent statistically significant results based on a two-sided significance level of 0.05

Two year mortality was 10.8%, 8.7%, and 44.4% in the none (0), mild (1), and moderate (2) groups, respectively. Univariable logistic regression identified moderate AI at 6 months (P = 0.001), age (P = 0.007), female sex (P = 0.016), co-existing pulmonary disease (P = 0.035), and preimplant moderate AI (P = 0.006) as predictors of 2 year mortality (Table 2). In a multivariable logistic regression model, moderate AI at 6 months (P = 0.024, OR: 4.32; 95% CI: 1.21–15.4) remained a significant predictor of 2 year mortality (Table 3). The Kaplan-Meier survival curve (Figure 1) showed a significant difference in rate of survival between groups over 2 years by log-rank test (P = 0.0003).

Table 2. - Odds Ratios/Coefficients from Univariable Regression Analysis for 2 Year Mortality, 6 Minute Walk Distance, and Right Heart Failure at 1 Year
Variable Odds Ratio (95% CI) p Coefficient (95% CI) p Odds Ratio (95% CI) p
2 Year Mortality 6 Minute Walk Distance (1 Year) Right Heart Failure (1 Year)
Age 1.05 (1.01–1.09) 0.007 −10 (−16 to−3) 0.005 1.02 (0.99–1.05) 0.115
Male sex 0.31 (0.12–0.80) 0.016 −136 (−477 to 206) 0.428 0.87 (0.34–2.20) 0.761
BMI 0.99 (0.93–1.05) 0.742 −10 (−30 to 11) 0.350 1.06 (1.01–1.11) 0.018
Cardiac output 1.05 (0.81–1.37) 0.695 −60 (−151 to 31) 0.190 1.04 (0.84–1.30) 0.703
Creatinine 1.39 (0.93–2.08) 0.111 −115 (−346 to 116) 0.324 0.77 (0.43–1.38) 0.384
Chronic kidney disease 1.55 (0.69–3.47) 0.289 −211 (−418 to −4) 0.046 1.22 (0.61–2.43) 0.578
Pulmonary disease 2.69 (1.07–6.75) 0.035 −150 (−433 to 133) 0.294 1.13 (0.47–2.75) 0.783
Prior cardiac surgery 1.40 (0.62–3.17) 0.419 −149 (−367 to 69) 0.177 1.33 (0.66–2.70) 0.427
Mitral regurgitation 1: 0.50 (0.11–2.18)
2: 0.69 (0.17–2.80)
3: 0.59 (0.13–2.70)
1: 0.355
2: 0.607
3: 0.497
1: 153
(−307 to 612)
2: 187
(−281 to 655)
3: 465
(−11 to 940)
1: 0.509
2: 0.426
3: 0.055
1: 0.36
(0.078–1.69)
2: 0.20
(0.043–0.95)
3: 0.25
(0.051–1.25)
1: 0.197
2: 0.043
3: 0.092
Aortic insufficiency 1: 2.09 (0.88–4.95)
2: 7.47 (1.80–30.9)
1: 0.094
2: 0.006
1: −36 (−258 to 187)
2: 44 (−434 to 522
1: 0.748
2: 0.854
1: 0.99 (0.50–1.96)
2: 0.83 (0.15–4.52)
1: 0.971
2: 0.827
Destination therapy 1.84 (0.79–4.28) 0.154 −428
(−616 to −239)
<0.0001 0.96 (0.49–1.87) 0.902
Aortic insufficiency at 6 months 1: 0.79 (0.31–2.01)
2: 6.60 (2.18–19.9)
1: 0.615
2: 0.001
1: −146 (−364 to 72)
2: −328 (−681 to 24)
1: 0.184
2: 0.067
1: 1.82 (0.90–3.67
2: 1.81 (0.53–6.19)
1: 0.093
2: 0.342
BMI, body mass index; CI, confidence interval.
Bold values represent statistically significant results based on a two-sided significance level of 0.05

Table 3. - Odds Ratio/Coefficients from Multivariable Regression Models for 2 Year Mortality
Two Year Mortality
Odds Ratio (95% CI) p
Age 1.05 (1.01–1.09) 0.021
Male sex 0.29 (0.10–0.88) 0.029
Pulmonary disease 1.82 (0.61–5.44) 0.283
Preimplant AI 1: 1.38 (0.51–3.69
2: 3.04 (0.56–16.4)
1: 0.526
2: 0.196
AI at 6 months 1: 0.83 (0.29–2.34)
2: 4.32 (1.21–15.4)
1: 0.730
2: 0.024
The model for 2 year mortality included age, gender, presence of pulmonary disease, preimplant AI, and AI at 6 months.
AI, aortic insufficiency.
Bold values represent statistically significant results based on a two-sided significance level of 0.05

Figure 1.
Figure 1.:
Kaplan-Meier survival curve based on the degree of aortic insufficiency at 6 months. AI, aortic insufficiency.

Fifty-six (36%) patients performed 6 minute walk testing at 1 year follow-up. Average 6 minute walk distance at 1 year was 1,301, 1,155, and 973 ft. in the none (0), mild (1), and moderate (2) groups, respectively, but was not significantly associated with AI status at 6 months (1: P = 0.184; 2: P = 0.067) on univariable analysis.

Right heart failure was identified in 25.6%, 38.6%, and 38.5% (0, 1, 2) of patients at 1 year, but was not significantly associated with AI status at 6 months (1: P = 0.093; 2: P = 0.342) on univariable analysis.

Discussion

Improvements in survival and quality of life in patients with VADs, combined with a shortage of donor availability will continue to lead to increasing numbers of patients on long-term LVAD support for both bridge to transplant and destination therapy (DT). As more long-term data become available, AI is being recognized more and more as a common sequela, and possibly a complication of long-term VAD therapy. Significant AI theoretically leads to reduced forward flow and end-organ malperfusion, but the existing literature has thus far failed to convincingly demonstrate a clear negative impact on survival and other health outcomes with less than severe AI.1,3,4,6

The major finding of this study is that in a multivariable model accounting for differences in age, gender, coexisting pulmonary disease, and pre-existing AI severity, moderate AI at 6 months was a significant predictor of 2 year mortality. Interestingly, there was a nonsignificant trend toward increased rate of right heart failure, and reduced functional exercise capacity in patients with both mild and moderate AI at 6 months compared with patients with no AI, even though a survival disadvantage exists. This further supports the significance of echocardiographic identification of AI in the absence of symptoms.

These results add to the growing literature addressing the clinical importance of new or worsening AI in patients on long-term VAD support. Most single-center studies thus far have failed to detect significantly worse outcomes in patients with moderate de novo post-LVAD AI, but there have been reports of increased rates of hospital readmission17 and even reduced survival in these patients.10,16 In Toda et al.’s10 retrospective series of 47 patients without AI at the time of implantation (median follow-up: 1,098 days), patients who had developed mild or greater AI by 1 year had significantly worse long-term survival (log-rank: P = 0.0195; 93% vs. 82% at 2 years) than patients without AI. In the largest study of this subject to date—an INTERMACS analysis of 10,603 patients—Truby et al.16 found that among patients surviving at least 1 year, those that developed new moderate-severe AI within that year had worse overall 2 year survival compared with those with no or mild AI (71.4% vs. 77.2%; P = 0.005). Similar to our cohort, however, there were significant differences between the groups, in age, sex, VAD strategy, preimplant AI, and multiple laboratory and hemodynamic values.16 While they compared patients who developed new moderate or severe AI within the first year to those who did not, we chose to stratify patients by AI severity at 6 months. This was done in an effort to capture the effect of LVAD-induced AI (25.9% of patients had developed new or worsening AI by this point, while 41.8% would go on to over the total duration of support), while somewhat controlling for the strong association between new/worsening AI and longer duration of support (in the Truby et al.16 cohort, median time on device was 25.6 months in the moderate/severe group and 12.1 months in the none/mild group). Furthermore, if AI severity at 6 months predicts mortality, this may present an opportunity for intervention earlier in the post-VAD course, or for more aggressive prophylactic measures in those patients most likely to develop moderate AI, especially as transcatheter valve replacement technology continues to advance.

Treatment of post-LVAD AI initially consists of medical optimization, including diuresis, afterload reduction, and optimization of pump settings.18–20 There is a paucity of prospective data regarding medical treatment, and current management techniques are mostly extrapolated from the management of chronic native AI in patients without VADs. In general, the goal is to reduce LV afterload, as well as aortic wall stress that might further contribute to aortic dilation.21 This strategy is mostly theoretical, however, and has not been convincingly proven to delay the progression or development of AI in patients with LVADs.

Optimal pump settings for patients with AI exist on a fine line. Higher speeds decrease AV opening (leading to additional commissure fusion and worsening AI) and can actually reverse the transaortic pressure gradient, again worsening AI.22 Lower speeds, on the other hand, theoretically slow the development/progression of AI by increasing the frequency of AV opening, but may result in systemic hypoperfusion, increased LV end-diastolic pressure, and therefore worsening symptoms of heart failure. In general, the lowest speed that allows for at least some AV opening while maintaining reasonable functional class should be used.8 Optimal device management by itself, however, is unlikely to be sufficient for symptomatic patients,22 and might be more important as a potential target for reducing the development of greater than or equal to moderate AI in asymptomatic patients. It is well established that nonopening AV’s are associated with greater development of AI,6,23–25 so it stands to reason that closer echocardiographic monitoring to maintain settings that allow valve opening might be useful in preventing or slowing the progression of LVAD-induced AI, as well any associated adverse outcomes. Prospective studies have yet to be published, however.

When medical management is ineffective, definitive treatment is required. Patients who develop severe, symptomatic LVAD-induced AI despite medical and pump optimization that are reasonable surgical candidates have undergone surgical repair or replacement of the valve with good outcomes.9 Yet, the decision to proceed with surgical intervention is often delayed, partly driven by a lack of corroborative data. For patients who are not suitable candidates for open surgery, less invasive transcatheter techniques, including transcatheter aortic valve replacement (TAVR), and other transcatheter techniques to simply close the valve, have been applied with some success.9,26–28 The data are limited to case series and reports, but various techniques show potential. Parikh et al.27 report a technique for closing the AV with an Amplatzer septal occlusion device in poor surgical candidates with severe post-LVAD AI. Two of five patients were alive at 30 days with no further AI and significantly reduced pulmonary capillary wedge (PCW) and left ventricular end-diastolic (LVED) pressures. Out of five total patients, however, two died in the postoperative period and another’s device embolized to the aortic arch and had to be retrieved. Russo et al.28 report a patient who underwent valve closure via a similar technique after failed post-LVAD AVR, with sustained improvements in symptoms and functional status at 2 months. Atkins et al.9 also report two patients treated percutaneously, with mixed results. One patient was treated with a ventricular septal defect occlusion device but had to undergo open surgery for device retrieval and aortic valvuloplasty after the device migrated to the LV. Another patient underwent transcatheter placement of a pulmonary valve within a previous bioprosthetic AV, with resolution of AI and functional improvement at short-term follow-up.

Although only approved for treatment of symptomatic aortic stenosis in patients at high and intermediate surgical risk, TAVR has also been used to treat severe LVAD-induced AI. Kozarek et al.26 described two patients who underwent TAVR with mixed outcomes; one patient did well, with good short-term symptomatic improvement, and one patient died in the early postoperative period after a procedure complicated by an improperly deployed valve. More data and experience will be needed to fully determine the role of TAVR in treating post-LVAD AI, but for now its successful application still faces multiple challenges. Importantly, the significant aortic valve calcification present in typical TAVR candidates (but often not present in post-LVAD AI) is important both as an anatomical landmark for proper valve placement and as an anchor that helps prevent valve migration or embolization. In addition, the unique physiology of continuous-flow mechanical circulatory support may increase the risk of valve migration toward the LV.26 Nevertheless, TAVR clearly shows potential, and if the data continue to indicate that TAVR and other transcatheter techniques are both safe and effective in the LVAD-induced AI population, and if further studies confirm the significant mortality risk associated with moderate AI in these patients, it may be worth investigating further the merits of treating moderate AI, even if asymptomatic, as long-term outcomes might be improved.

An alternative strategy might be to prophylactically close aortic valves at the time of device implantation in patients who are at highest risk to develop moderate or severe AI during VAD support (DT, greater baseline aortic root diameter, female sex, older age, smaller body surface area, lower preimplant ejection fraction, etc.).8,29 It is unclear, however, from the current literature whether this is likely to be an effective strategy. Before making radical management recommendations, more thoughtful studies are warranted.

Multiple studies have found concomitant AV procedures in patients with pre-existing, greater than or equal to moderate AI, including outflow tract closure, to be safe and effective, with outcomes similar to those of patients not requiring a valve procedure.13 In fact, International Society for Heart and Lung Transplantation guidelines recommend consideration for surgical intervention for greater than mild AI at the time of VAD implant.30 Robertson et al.,15 however, found that valve closure was associated with significantly worse survival than AV repair or replacement in patients with moderate or greater AI at the time of implantation. The reason for this was unclear, though, as valve closure was actually the most durable technique for preventing redevelopment of moderate or severe AI (5%; P < 0.0001). Furthermore, these data may not apply to patients who have not yet developed hemodynamically significant AI.

This study had multiple limitations. It was done at a single center, and therefore confounding in echocardiography methods/interpretation, LVAD management, surgical technique, etc. that may have affected development, assessment, or complications of AI cannot be excluded. Given its retrospective nature, we are unable to assess a causal relationship between AI and mortality in this patient population. Finally, the limited number of patients reduces the effectiveness of multivariable modeling. Regarding the secondary endpoint of 6 minute walk distance at 1 year, the relatively small fraction of patients who actually performed the test (35%) limits both the power of statistical analysis and the quality of any conclusions that might be drawn from the results.

In conclusion, moderate AI at 6 months post-LVAD implant is associated with lower 2 year survival. More aggressive management strategies targeting AI development in long-term LVAD patients, as well as aggressive correction of moderate AI may be warranted.

References

1. Cowger J, Pagani FD, Haft JW, Romano MA, Aaronson KD, Kolias TJ. The development of aortic insufficiency in left ventricular assist device-supported patients. Circ Heart Fail 2010; 3:668–674.
2. Pak SW, Uriel N, Takayama H, et al. Prevalence of de novo aortic insufficiency during long-term support with left ventricular assist devices. J Heart Lung Transplant 2010; 29:1172–1176.
3. Imamura T, Kinugawa K, Fujino T, et al. Aortic insufficiency in patients with sustained left ventricular systolic dysfunction after axial flow assist device implantation. Circ J 2015; 79:104–111.
4. Holley CT, Fitzpatrick M, Roy SS, et al. Aortic insufficiency in continuous-flow left ventricular assist device support patients is common but does not impact long-term mortality. J Heart Lung Transplant 2017; 36:91–96.
5. Cowger JA, Aaronson KD, Romano MA, Haft J, Pagani FD. Consequences of aortic insufficiency during long-term axial continuous-flow left ventricular assist device support. J Heart Lung Transplant 2014; 33:1233–1240.
6. Aggarwal A, Raghuvir R, Eryazici P, et al. The development of aortic insufficiency in continuous-flow left ventricular assist device-supported patients. Ann Thorac Surg 2013; 95:493–498.
7. Patil NP, Sabashnikov A, Mohite PN, et al. De novo aortic regurgitation after continuous-flow left ventricular assist device implantation. Ann Thorac Surg 2014; 98:850–857.
8. Bouabdallaoui N, El-Hamamsy I, Pham M, et al. Aortic regurgitation in patients with a left ventricular assist device: A contemporary review. J Heart Lung Transplant 2018; 18:31541–31549.
9. Atkins BZ, Hashmi ZA, Ganapathi AM, et al. Surgical correction of aortic valve insufficiency after left ventricular assist device implantation. J Thorac Cardiovasc Surg 2013; 146:1247–1252.
10. Toda K, Fujita T, Domae K, Shimahara Y, Kobayashi J, Nakatani T. Late aortic insufficiency related to poor prognosis during left ventricular assist device support. Ann Thorac Surg 2011; 92:929–934.
11. Bryant AS, Holman WL, Nanda NC, et al. Native aortic valve insufficiency in patients with left ventricular assist devices. Ann Thorac Surg 2006; 81:e6–e8.
12. Mudd JO, Cuda JD, Halushka M, Soderlund KA, Conte JV, Russell SD. Fusion of aortic valve commissures in patients supported by a continuous axial flow left ventricular assist device. J Heart Lung Transplant 2008; 27:1269–1274.
13. Goda A, Takayama H, Pak SW, et al. Aortic valve procedures at the time of ventricular assist device placement. Ann Thorac Surg 2011; 91:750–754.
14. Adamson RM, Dembitsky WP, Baradarian S, et al. Aortic valve closure associated with heartmate left ventricular device support: Technical considerations and long-term results. J Heart Lung Transplant 2011; 30:576–582.
15. Robertson JO, Naftel DC, Myers SL, et al. Concomitant aortic valve procedures in patients undergoing implantation of continuous-flow left ventricular assist devices: An INTERMACS database analysis. J Heart Lung Transplant 2015; 34:797–805.
16. Truby LK, Garan AR, Givens RC, et al. Aortic insufficiency during contemporary left ventricular assist device support: Analysis of the INTERMACS registry. JACC Heart Fail 2018; 6:951–960.
17. Mano A, Gorcsan J, Teuteberg J, et al. Incidence and impact of de novo aortic insufficiency following continuous flow LVADs implantation. J Heart Lung Transplant 2012; 31:S22.
18. Rajagopal K, Daneshmand MA, Patel CB, et al. Natural history and clinical effect of aortic valve regurgitation after left ventricular assist device implantation. J Thorac Cardiovasc Surg 2013; 145:1373–1379.
19. Klotz S, Burkhoff D, Garrelds IM, Boomsma F, Danser AH. The impact of left ventricular assist device-induced left ventricular unloading on the myocardial renin-angiotensin-aldosterone system: Therapeutic consequences? Eur Heart J 2009; 30:805–812.
20. Klotz S, Danser AH, Foronjy RF, et al. The impact of angiotensin-converting enzyme inhibitor therapy on the extracellular collagen matrix during left ventricular assist device support in patients with end-stage heart failure. J Am Coll Cardiol 2007; 49:1166–1174.
21. Fine NM, Park SJ, Stulak JM, et al. Proximal thoracic aorta dimensions after continuous-flow left ventricular assist device implantation: Longitudinal changes and relation to aortic valve insufficiency. J Heart Lung Transplant 2016; 35:423–432.
22. Jorde UP, Uriel N, Nahumi N, et al. Prevalence, significance, and management of aortic insufficiency in continuous flow left ventricular assist device recipients. Circ Heart Fail 2014; 7:310–319.
23. Cowger J, Rao V, Massey T, et al. Comprehensive review and suggested strategies for the detection and management of aortic insufficiency in patients with a continuous-flow left ventricular assist device. J Heart Lung Transplant 2015; 34:149–157.
24. John R, Mantz K, Eckman P, Rose A, May-Newman K. Aortic valve pathophysiology during left ventricular assist device support. J Heart Lung Transplant 2010; 29:1321–1329.
25. da Rocha E Silva JG, Meyer AL, Eifert S, et al. Influence of aortic valve opening in patients with aortic insufficiency after left ventricular assist device implantation. Eur J Cardiothorac Surg 2016; 49:784–787.
26. Kozarek K, Minhaj MM, Chaney MA, et al. Transcatheter aortic valve replacement for left ventricular assist device-induced aortic insufficiency. J Cardiothorac Vasc Anesth 2018; 32:1982–1990.
27. Parikh KS, Mehrotra AK, Russo MJ, et al. Percutaneous transcatheter aortic valve closure successfully treats left ventricular assist device-associated aortic insufficiency and improves cardiac hemodynamics. JACC Cardiovasc Interv 2013; 6:84–89.
28. Russo MJ, Freed BH, Jeevanandam V, et al. Percutaneous transcatheter closure of the aortic valve to treat cardiogenic shock in a left ventricular assist device patient with severe aortic insufficiency. Ann Thorac Surg 2012; 94:985–988.
29. Holtz J, Teuteberg J. Management of aortic insufficiency in the continuous flow left ventricular assist device population. Curr Heart Fail Rep 2014; 11:103–110.
30. Feldman D, Pamboukian SV, Teuteberg JJ, et al.; International Society for Heart and Lung Transplantation: The 2013 international society for heart and lung transplantation guidelines for mechanical circulatory support: Executive summary. J Heart Lung Transplant 2013; 32:157–187.
Keywords:

left ventricular assist device; aortic regurgitation; aortic insufficiency; mortality; de novo AI; de novo AR; de novo; LVAD-induced; right heart failure; functional exercise capacity; 6 minute walk

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