Full Terms & Conditions of access and use can be found athttps://www.tandfonline.com/action/journalInformation?journalCode=ushj20

Structural HeartThe Journal of the Heart Team

ISSN: 2474-8706 (Print) 2474-8714 (Online) Journal homepage: https://www.tandfonline.com/loi/ushj20

Transcatheter Aortic Valve Replacement in LeftVentricular Assist Device Patients with AorticRegurgitation

Mark N. Belkin, Teruhiko Imamura, Takeo Fujino, Anthony J. Kanelidis,Luise Holzhauser, Imo Ebong, Nikhil Narang, John E. Blair, Sandeep Nathan,Jonathan D. Paul, Atman P. Shah, Ben Bow Chung, Ann Nguyen, Bryan Smith,Sara Kalantari, Jayant Raikhelkar, Takeyoshi Ota, Valluvan Jeevanandam,Gene Kim, Daniel Burkhoff, Gabriel Sayer & Nir Uriel

To cite this article: Mark N. Belkin, Teruhiko Imamura, Takeo Fujino, Anthony J. Kanelidis,Luise Holzhauser, Imo Ebong, Nikhil Narang, John E. Blair, Sandeep Nathan, Jonathan D. Paul,Atman P. Shah, Ben Bow Chung, Ann Nguyen, Bryan Smith, Sara Kalantari, Jayant Raikhelkar,Takeyoshi Ota, Valluvan Jeevanandam, Gene Kim, Daniel Burkhoff, Gabriel Sayer & Nir Uriel(2020) Transcatheter Aortic Valve Replacement in Left Ventricular Assist Device Patients withAortic Regurgitation, Structural Heart, 4:2, 107-112, DOI: 10.1080/24748706.2019.1706793

To link to this article: https://doi.org/10.1080/24748706.2019.1706793

View supplementary material Published online: 25 Feb 2020.

Submit your article to this journal Article views: 60

View related articles View Crossmark data

ORIGINAL RESEARCH

Transcatheter Aortic Valve Replacement in Left Ventricular Assist Device Patientswith Aortic RegurgitationMark N. Belkin, MD a, Teruhiko Imamura, MD, PhDa,b, Takeo Fujino, MD, PhDa, Anthony J. Kanelidis, MDa,Luise Holzhauser, MDa, Imo Ebong, MDc, Nikhil Narang, MDd, John E. Blair, MDa, Sandeep Nathan, MDa,Jonathan D. Paul, MDa, Atman P. Shah, MDa, Ben Bow Chung, MDa, Ann Nguyen, MDa, Bryan Smith, MDa,Sara Kalantari, MDa, Jayant Raikhelkar, MDe, Takeyoshi Ota, MD, PhDf, Valluvan Jeevanandam, MDf, Gene Kim, MDa,Daniel Burkhoff, MD, PhDg, Gabriel Sayer, MDe, and Nir Uriel, MD, MSce

aDepartment of Medicine, University of Chicago Medical Center, Chicago, Illinois, USA; bDepartment of Medicine, University of Toyama, Toyama,Japan; cDepartment of Medicine, University of California-Davis, Sacramento, California, USA; dAdvocate Heart Institute, Advocate Christ MedicalCenter, Oak Lawn, Illinois, USA; eDivision of Cardiology, Columbia University Irving Medical Center, , New York, USA; fDepartment of Surgery,University of Chicago Medical Center, Chicago, Illinois, USA; gColumbia University Medical Center, and Cardiovascular Research Foundation, NewYork, USA

ABSTRACTBackground: Development of aortic regurgitation (AR) following left ventricular assist device (LVAD) implantation is common,and it is associated with a poor prognosis. Transcatheter aortic valve replacement (TAVR) has become a mainstay therapy forpatients with severe aortic stenosis, with an off-label use for severe AR. The aim of this study was to assess the feasibility anddurability of TAVR in LVAD patients with significant AR.

Methods: We evaluated all LVAD patients within our database that underwent TAVR for AR. Clinical and echocardiographic datawere collected before and after TAVR procedure. Aortic regurgitant fraction (RF) was calculated using outflow graft Dopplerechocardiography.

Results: Seven patients underwent nine attempted TAVR procedures. Median age was 69 (IQR 63–73) and 43% were female.Median time from LVAD to TAVR was 23 (IQR 17–52) months. One procedure was aborted due to vascular complications, and onepatient underwent two separate procedures 22 months apart. Five patients (71%) survived over median follow-up of 9 (IQR 6–23)months. Two patients died of paravalvular complications following device deployment. Procedural success was achieved in 67%of attempts, with significant improvement in RF from 44.8% (IQR 37.6–63.6) pre-procedurally to 28.1% (IQR 0.30–29.6) at six-month follow-up. Qualitatively, mild or moderate paravalvular leak was noted on all surviving patients at one- and six-monthfollow-up. There was significant improvement in right ventricular function at 6-month follow-up.

Conclusion: TAVR is a reasonable option for treating LVAD-induced AR. Longer follow-up and larger cohorts are needed to assessthe durability and long-term efficacy of this procedure.

Abbreviations: AR: Aortic regurgitation; AV: Aortic valve; LV: Left ventricle; LVAD: Left ventricular assist device; LVIDd: Leftventricular internal dimension at end-diastole; LVIDs: Left ventricular internal dimension at end-systole; PAPi: Pulmonary arterypulsatility index; RA: Right atrial; RF: Regurgitant fraction; RV: Right ventricle; RVEDA: Right ventricular end-diastolic area; RVFAC:Right ventricular fractional area change; RVSP: Right ventricular systolic pressure; TAPSE: tricuspid annular plane systolic excursion;TAVR: Transcatheter aortic valve replacement; TV: Tricuspid valve

ARTICLE HISTORY Received 3 June 2019; Revised 25 October 2019; Accepted 14 November 2019

KEYWORDS TAVI; TAVR; LVAD; aortic regurgitation; percutaneous valve repair

Introduction

Left ventricular assist device (LVAD) implantation is an increas-ingly common treatment for advanced heart failure, with over22,000 FDA-approved devices implanted from 2006 to 2016. Thevast majority of these implants are continuous-flow LVADs,which are associated with the development of aorticregurgitation (AR) in 6-32% of patients during the first year,and up to 24-33% at 3 years.1–5 There are two mechanisms

hypothesized to cause AR in these patients: first, lack of aorticvalve (AV) opening can cause fusion and eventual deteriorationof the leaflet commissures.2,6,7 Second, a reverse pressure gradi-ent across the AV caused by the continuous unloading of the leftventricle can lead to an increase in shear stress and developmentof de novo, or worsening of existing, AR.8

AR in LVAD patients is associated with higher central venouspressure and pulmonary capillary wedge pressure, and lowerpulmonary artery pulsatility index (PAPi) compared to those

CONTACT Nir Uriel nu2126@cumc.columbia.edu Professor of Medicine, Director of NYP Heart Failure, Heart Transplant & Mechanical Circulatory SupportPrograms, Columbia University Irving Medical Center, Weill Cornell Medicine, 622 W. 168th St., PH 4-129, New York, NY 10032, USA.

Supplemental data for this article can be accessed here.

STRUCTURAL HEART2020, VOL. 4, NO. 2, 107–112https://doi.org/10.1080/24748706.2019.1706793

© 2020 Cardiovascular Research Foundation

without AR.9 Additionally, development of moderate-to-severeAR following LVAD implantation is associated with lower systolicblood pressure and cardiac output when compared to those withnone-to-mild AR, as well as an increase in hospitalizations andreduced survival.5

Treatment options for AR in LVAD patients include devicespeed optimization, surgical valve intervention, including clo-sure, percutaneous valve replacement or closure, and bothurgent and non-urgent cardiac transplantation.2,10,11 The cur-rent International Society of Heart and Lung Transplantationguidelines do not address management of de novo or worsen-ing AR following LVAD.12

Transcatheter aortic valve replacement (TAVR) has becomea common therapy for high- and intermediate-risk patients withsevere aortic stenosis, and recent data also support its use forlow-risk patients.13–17 While TAVR does not have a Food andDrug Administration indication for the treatment of AR, it hasbeen used successfully for severe AR.18 There are limited studiesevaluating the use of TAVR for AR in LVAD patients.10,11,19

The aim of this study was to assess the feasibility and durabilityof TAVR in LVAD patients with severe AR.

Materials and methods

We evaluated all patients who underwent LVAD implantationat our institution and subsequently underwent TAVR for ARbetween April 2014 and December 2018. Retrospective datawere collected in accordance with the protocol approved byour institution’s IRB. Informed consent was deemed unneces-sary by the IRB due to the retrospective nature of this analysis.

Clinical, laboratory, and echocardiographic data were col-lected before and after the TAVR procedure. Choice of valveimplantedwas dependent upon aortic root size, calcification, andoperator preference. All patients underwent a cardiac CT scanprior to TAVR for assistance in procedural planning. Clinicaldata included time from LVAD to TAVR, length of post-TAVR intensive care unit admission, length of hospitalization,and survival. Laboratory data included a complete blood count,basic metabolic panel, n-terminal pro-brain natriuretic peptide,troponin, and lactate dehydrogenase. These values were collectedpre-procedurally, as well as approximately one-day, one-month,and six-months post-procedure, as available per routine clinicalcare. Transthoracic echocardiography (TTE) was performedprior to the procedure, immediately following the procedureand at approximately one and 6months following the procedure.AR was measured by using outflow graft velocities to calculatethe AV regurgitant fraction (RF). This was calculated by usingpulse-wave Doppler to measure the systolic velocity, diastolicvelocity, and diastolic slope across the left ventricular (LV) out-flow graft, as previously described (Supplemental Figure 1 forequation).20 Furthermore, TTE was used to assess right ventri-cular end-diastolic area (RVEDA) right ventricular fractionalarea change (RVFAC), right ventricular systolic pressure(RVSP), tricuspid annular plane systolic excursion (TAPSE),tricuspid valve (TV) S’, tricuspid regurgitation (TR) grade, rightatrial (RA) area, left ventricular internal dimension at end-diastole (LVIDd), left ventricular internal dimension at end-systole (LVIDs), paravalvular leak, and frequency ofAVopening,

as available. Paravalvular leaks were assessed according to ValveAcademic Research Consortium-2 criteria.

Statistical analyses were performed using SPSS Statistics 22(SPSS Inc, Armonk, IL, USA). A two-tailed p-value < 0.05 wasconsidered significant. Continuous variables were expressed asmedian and quartiles. Changes in variables between two timepoints were assessed by Wilcoxon signed-rank test, and thoseamong multiple time points were assessed by Friedman test.

Results

Seven patients underwent nine TAVR procedures, including onerepeat procedure following degeneration of the first valve, with thedevelopment of recurrent moderate-severe AR, after 22 months.A second patient had his procedure aborted due to a vascularcomplication, with successful TAVR eventually performed 28days later. Median age was 69 years (IQR 63–73) and threepatients were female. Four of the seven patients had ischemiccardiomyopathy, and five patients had their LVAD implanted asdestination therapy. Median time from LVAD to TAVR was 23(IQR 17–52) months. Implanted valves included the EdwardsSapien 3™ (sizes: one 23 mm, one 26 mm, and three 29 mmvalves), Medtronic CoreValve™ (sizes: three 31 mm valves), andMedtronic Evolut R™ (size: one 34 mm valve) (Table 1).

Procedural success was achieved in six of nine (67%) proce-dural attempts. One patient accounted for one successful and oneunsuccessful procedure, as his initial procedurewas aborted due tovascular complications, but he underwent successful TAVR 28days later, as previously stated. In two other patients, inadequatevalve fixation led to severe paravalvular leaks with progression tocardiogenic shock and death within the first day. In the firstpatient, the initial valve was displaced into the left ventricularoutflow tract (LVOT), and the second valve was displaced intothe aortic root. In the second patient, the valvewas displaced in theLVOT following deployment. In the five patients with successfulvalve deployment, ARwas improved significantly with a reductionof RF from44.8% (IQR37.6–63.6) pre-procedurally to 27.3% (IQR

Table 1. Baseline and procedural characteristics.

Patients (n) 7

Procedures (n) 9

Age (yrs) 69 (IQR 63–73)

Female Sex (%) 3 (43%)

ICM (%) 4 (57%)

NICM (%) 3 (43%)

BTT (%) 2 (29%)

DT (%) 5 (71%)

Time LVAD to TAVR (months) 23 (IQR 17–52)

LVAD

HeartWare HVAD 2 (25%)

Heartmate II 5 (62%)

Heartmate 3 1 (13%)

TAVR

Medtronic CoreValve™ 3 (33%)

Medtronic Evolut R™ 1 (11%)

Edwards Sapien 3™ 5 (56%)

Notes. BTT = bridge-to-transplant, DT = destination therapy, ICM = ischemiccardiomyopathy, LVAD = left ventricular assist device, NICM = non-ischemiccardiomyopathy, TAVR = Transcatheter aortic valve replacement.

108 M. N. BELKIN ET AL.: TRANSCATHETER AORTIC VALVE REPLACEMENT STRUCTURAL HEART

8.5–30.0, p = 0.041) immediately post-TAVR. RF at 1 month was26.1% (IQR 10.6–29.9) and at 6 months was 28.1% (IQR 0.30–29.6), unchanged from the immediate post-procedure period (p =0.81) (Figure 1, Table 2, Supplemental Table I). Mild or moderateparavalvular leakwas noted on five of the six surviving patients onimmediate post-procedure TTE as well as at six-month follow-up,though the AV was not well visualized in one of the six patients.Prior to the TAVR, the AVwas noted to be opening in three of theeight patients, while immediately post-procedure all of the valvesin the surviving patients was closed. On a 6-month follow-up, fourof six valves were not opening, though, again, one valve was notvisualized.

There was a wide range of calcification noted among theincluded patients (Table 3). The median time for the length ofthe procedure was 146 (IQR 79–150) minutes. Median lengthof cardiac care unit (CCU) stay post-procedure was 1 day (IQR1–1 day), and the length of hospitalization post-procedure was7 days (IQR 3–9 days) (Table 3). There were two vascularcomplications, one involving a defective closure device thatrequired surgical removal, and a second post-procedural pseu-doaneurysm noted on ultrasound that was found to be a largegroin hematoma on surgical exploration. No patients requiredtemporary or permanent pacing post-procedure.

Following the TAVR procedure, five of seven patients(71%) survived with two expiring of peri-procedural com-plications within the first day, as previously described. Ofthe five patients without peri-procedural complications,there was 100% survival at 10 (IQR 9–43) months of fol-low-up. In the 6 months prior to, and following, the TAVRprocedure there were 10 and 6 total non-elective hospitali-zations, respectively, among the six patients that survivedthe procedure (Supplemental Table II). There were no peri-procedural or post-procedural strokes. Pre- and post-procedural serum laboratory values are noted inSupplemental Table III, and were only notable fora significant decrease in blood urea nitrogen (p = 0.03),and an increase in platelet count (p = 0.03) following theprocedure.

Table 2. Regurgitant fraction (%) measurements of AR by case.

Patient Pre-TAVR Post-procedure 1-month 6-month

1 44.8 NA NA NA

2A 63.6 0.3 21 0.3

2B 34.4 16.8 0.3 0.3

3 69.1 30 NV 28.1

4 38.9 NV 26.1 NV

5A 37.6 NA NA NA

5B 37.6 27.3 30.4 29.6

6 44.8 30 29.5 29.7

7 NV NV NA NA

Notes. NA = not applicable, NV = not visualized.

Table 3. Individual peri-procedural details.

Patient LVAD Valve Size Procedure Length(mm) CCU LOS Hospital LOS Discharge Survival Aortic Calcification

1 HMII Medtronic Core Valve™(2) 31 mm 317 0 0 No Mild calcification of thoracic aorta

2A HMII Medtronic Core Valve™ 31 mm 207 2 12 Yes Minimal

2B HMII Edwards-Sapien 3™ 29 mm 146 0 7 Yes None

3 HMII Edwards-Sapien 3™ 23 mm 120 3 8 Yes Mild

4 HVAD Edwards-Sapien 3™ 26 mm 71 1 4 Yes None

5A HM3 NA NA 146 1 54 Yes None

5B HM3 Medtronic Evolut R™ 34 mm 150 1 26 Yes None

6 HMII Edwards-Sapien 3™ 29 mm 76 1 7 Yes Aortic leaflet calcifications

7 HVAD Edwards-Sapien 3™ 29 mm 79 1 1 No None

Notes. CCU = cardiovascular intensive care unit, HMII = HeartMate II, HM3 = HeartMate 3, HVAD = HeartWare HVAD, LOS = length of stay, LVAD = left ventricularassist device.

Figure 1. Peri-procedural change in aortic regurgitant fraction.

M. N. BELKIN ET AL.: TRANSCATHETER AORTIC VALVE REPLACEMENT STRUCTURAL HEART 109

Right ventricular (RV) function improved at six-monthfollow-up with significant improvement in RVEDA: 23.6(IQR 19.2–37.7) to 17.1 (IQR 15.7–20.6), p = 0.043, andRVFAC: 0.17 (IQR 0.12–0.25) to 0.29 (IQR 0.21–0.37), p =0.042. There were no significant changes in TAPSE, TV S’, TRgrade, RVSP, or RA area (p > 0.05 for all). In regards to leftventricular echocardiographic dimensions, there was nochange in LVIDd, but a small, statistically significant increasein LVIDs at six-month follow-up (Table 4).

Discussion

Hemodynamically significant AR is an increasingly prevalentcomplication of LVAD therapy as the technology has becomemore widespread and durable.1 Up to one-third of patientsdevelop moderate-to-severe AR over 1–3 years post-operatively, and to-date, there is no consensus on appropriatemanagement.2–4 There are limited data published on the use ofTAVR in LVAD patients with AR, with a recently publishedsingle-center, retrospective case series of nine patients, under-going nine procedures, the largest study to date.10 TAVR wassuccessfully performed and reductions of AR were achievedbased on visual estimation from severe to none-to-trace usingtraditional echocardiographic methods. In our study, we usednovel echocardiographic parameters to more accurately quanti-tate AR, and we provide the first investigation of the impact ofTAVR on RV function.We demonstrated that TAVR led to bothan improvement in AR, as well as a significant and meaningfulimprovement in RV function.

Our results indicate that TAVR may be considered asa percutaneous option to treat moderate-severe AR in LVADpatients. Our initial cohort has a mortality rate of 29%, whichmay reflect a learning curve regarding patient selection andprocedural approach, but also highlights the potential limita-tions of this technology that was originally designed for implan-tation in a calcified aortic annulus in the context of aorticstenosis. In particular, one of the two patients who expiredlacked sufficient perivalvular calcification to ensure appropriatefixation of the valve, though three procedures were successfullycompleted in patients without perivalvular calcification noted on

pre-procedural imaging. Similarly, two of the nine patients in thestudy by Yehya et al. also had peri-procedural migration of theTAVR into the LVOT requiring snaring and deployment ofa second valve.10 The development of percutaneous valves spe-cifically designed for the treatment of AR may obviate thesecomplications in the future. We want to further underscore theimportance of procedural experience when approaching TAVRin the LVAD patient. Management of valve expansion in thesetting of the suction effect from the LVAD inflow cannularequires technical expertise. Operators with TAVR experiencein the general population should proceed with caution whentranslating their experience to the LVAD population.Furthermore, while TAVR is one potential treatment for AR,options ranging frommedical to surgical management should bediscussed with a multi-disciplinary team including advancedheart failure cardiologists, interventional cardiologists, and car-diac surgeons experienced in the care of LVAD patients.

The 71% survival rate noted in our study over a median 9months of follow-up, and the conditional 100% survival inpatients surviving beyond the first post-procedural day is com-parable to the survival reported in the study by Yehya et al. (89%at 6 months and 56% at 12 months), and is significantly higherthan the 35% survival rate at 20 months that was reported byPhan et al.10,11 In comparison to other percutaneous treatmentsof AR in LVAD patients, the study by Phan et al. is the largestpublished study of the use of percutaneous occluder devices fortreatment of AR in LVAD patients, and the authors report zeropatients survived beyond 20 months.11 The improved survivalnoted in our study and the one by Yehya et al. highlight theimportance of operator experience at a single center, as com-pared to the multiple centers with single cases evaluated in themeta-analysis by Phan et al.10,11

Although further data are needed, we are encouraged by thelack of increase in AR over the 6 months following TAVR.However, as shown by the deterioration of the valve in one ofour patients, requiring a second TAVR after 22 months, closeechocardiographic surveillance of the implanted AV is essential inthese patients. The improvement in RV function over time fol-lowing TAVR is another important finding. Our previous studythat investigated the hemodynamics of LVAD patients with ARshowed worse RV function in these patients, as measured byPAPi.9 This raised the question of whether AR was leading toRV failure as a result of increased filling pressures and RV after-load, or whether RV failure was leading to AR due to inadequateLV filling to maintain an open AV. The findings of this studysuggest that the correction of the AR is associated with improvedRV function, supporting the hypothesis that AR is the trigger forRV failure. The lack of decrease in LV size (and small increase inLVIDs) following TAVRmay be related to the small study size, ormay reflect the effects of increased flow from the RV balancing outthe decrease in volume overload from treatment of AR.

Limitations

This case series is a single-center experience that may not beapplicable to other centers. Furthermore, the outcomesmay repre-sent the learning curve inherent in this procedure, and may notreflect outcomes that could be achieved with greater experience.We do not have hemodynamic data to corroborate our

Table 4. Peri-procedural changes in echocardiographic assessment of rightventricular function.

Pre Post 6Mo p-value

TAPSE, cm 0.7 (0.5, 1.5) 1.0 (0.9, 1.6) 0.90

TV S’, cm/sec 5.1 (4.2, 8.3) 7.0 (6.6, 9.0) 0.59

TR grade 1.0 (0.5, 3.0) 0.5 (0, 1.5) 0.71

RA area, cm2 20.4 (11.7, 26.5) 10.9 (10.5, 15.4) 0.10

RVEDA, cm2 23.6 (19.2, 37.7) 17.1 (15.7, 20.6) 0.043*

RVFAC 0.17 (0.12, 0.25) 0.29 (0.21, 0.37) 0.042*

RVSP, mmHg 25 (18, 37) 34 (15, 38) 0.66

LVIDd 6.0 (5.1, 7.0) 6.2 (5.2, 7.5) 0.12

LVIDs 5.5 (4.4, 6.5) 5.7 (5.0, 7.0) 0.027*

Notes. *p-value < 0.05, LVIDd = left ventricular internal dimension at end-diastole, LVIDs = left ventricular internal dimension at end-systole, RA =right atrial, RVEDA = right ventricular end-diastolic area, RVFAC = rightventricular fractional area change (RVFAC), RVSP = right ventricular systolicpressure, TAPSE = tricuspid annular plane systolic excursion, TR = tricuspidregurgitation, TV S’ = tricuspid valve S’. Variables were compared by Wilcoxonsinged-rank test.

110 M. N. BELKIN ET AL.: TRANSCATHETER AORTIC VALVE REPLACEMENT STRUCTURAL HEART

echocardiographic findings regarding improvement in RV func-tion. The diversity of TAVR valves used may further limitgeneralizability.

Conclusion

TAVR is a reasonable therapy for treating LVAD-related AR.Physician experience and technical expertise are critical forthese procedures due to the unique hemodynamic effectsassociated with the LVAD, and its effect on valve deployment.Larger cohorts with longer follow-up are necessary to furtherevaluate the safety and long-term efficacy of this procedure.

ORCID

Mark N. Belkin http://orcid.org/0000-0002-9489-4572

Funding

The authors report no funding in support of this paper.

Disclosure statement

M.N. Belkin: None. T. Imamura: None. T. Fujino: None. A.J. Kanelidis:None. L. Holzhauser: None. I. Ebong: None. N. Narang: None. J.E. Blair:None. S. Nathan: Consultant Medtronic. J.D. Paul: None. A.P. Shah: None.B. Chung: None. A. Nguyen: None. B. Smith: None. S. Kalantari: None.J. Raikhelkar: None. T. Ota: None, V. Jeevanandam: Consultant Abbott,Medtronic, NuPulseCV. G. Kim: None. D. Burkhoff: Serves as an AssociateEditor for Structural Heart. G. Sayer: none. N. Uriel: Grant/ResearchSupport Medtronic, Abbott.

References

1. Kirklin JK, Pagani FD, Kormos RL, Stevenson LW, Blume ED,Myers SL, et al. Eighth annual INTERMACS report: special focuson framing the impact of adverse events. J Heart Lung Transplant.2017;36(10):1080–1086. Epub 2017/ 09/26. doi: 10.1016/j.hea-lun.2017.07.005. PubMed PMID: 28942782.

2. Jorde UP, Uriel N, Nahumi N, Bejar D, Gonzalez-Costello J,Thomas SS, et al. Prevalence, significance, and management of aorticinsufficiency in continuous flow left ventricular assist device recipients.Circ Heart Fail. 2014;7(2):310–319. Epub 2014/01/15. doi: 10.1161/CIRCHEARTFAILURE.113.000878. PubMed PMID: 24415682.

3. Soleimani B, Haouzi A, Manoskey A, Stephenson ER, El-Banayosy A, Pae WE. Development of aortic insufficiency inpatients supported with continuous flow left ventricular assistdevices. Asaio J. 2012;58(4):326–329. Epub 2012/ 05/10. doi:10.1097/MAT.0b013e318251cfff. PubMed PMID: 22569164.

4. Holley CT, Fitzpatrick M, Roy SS, Alraies MC, Cogswell R,Souslian L, et al. Aortic insufficiency in continuous-flow leftventricular assist device support patients is common but doesnot impact long-term mortality. J Heart Lung Transplant.2017;36(1):91–96. Epub 2016/ 09/14. doi: 10.1016/j.hea-lun.2016.07.018. PubMed PMID: 27623098.

5. Truby LK, Garan AR, Givens RC, Wayda B, Takeda K,Yuzefpolskaya M, et al. Aortic insufficiency during contemporaryleft ventricular assist device support: analysis of the INTERMACSregistry. JACC Heart Fail. 2018;6(11):951–960. Epub 2018/11/06.doi: 10.1016/j.jchf.2018.07.012. PubMed PMID: 30384913;PubMed Central PMCID: PMCPMC6217859.

6. Pak SW, Uriel N, Takayama H, Cappleman S, Song R,Colombo PC, et al. Prevalence of de novo aortic insufficiency

during long-term support with left ventricular assist devices.J Heart Lung Transplant. 2010;29(10):1172–1176. Epub 2010/07/14. doi: 10.1016/j.healun.2010.05.018. PubMed PMID: 20619680.

7. Mudd JO, Cuda JD, Halushka M, Soderlund KA, Conte JV,Russell SD. Fusion of aortic valve commissures in patientssupported by a continuous axial flow left ventricular assistdevice. J Heart Lung Transplant. 2008;27(12):1269–1274. Epub2008/12/09. doi: 10.1016/j.healun.2008.05.029. PubMed PMID:19059105.

8. Holtz J, Teuteberg J. Management of aortic insufficiency inthe continuous flow left ventricular assist device population.Curr Heart Fail Rep. 2014;11(1):103–110. Epub 2013/11/07.doi: 10.1007/s11897-013-0172-6. PubMed PMID: 24193452.

9. Sayer G, Sarswat N, Kim GH, Adatya S, Medvedofsky D,Rodgers D, et al. The hemodynamic effects of aortic insufficiencyin patients supported with continuous-flow left ventricular assistdevices. J Card Fail. 2017;23(7):545–551. Epub 2017/04/25. doi:10.1016/j.cardfail.2017.04.012. PubMed PMID: 28435003.

10. Yehya A, Rajagopal V, Meduri C, Kauten J, Brown M, Dean L, et al.Short-term results with transcatheter aortic valve replacement fortreatment of left ventricular assist device patients with symptomaticaortic insufficiency. J Heart Lung Transplant. 2019. Epub 2019/03/23.doi: 10.1016/j.healun.2019.03.001. PubMed PMID: 30898555. 38920–926

11. Phan K, Haswell JM, Xu J, Assem Y, Mick SL, Kapadia SR, et al.Percutaneous transcatheter interventions for aortic insufficiency incontinuous-flow left ventricular assist device patients: a systematicreview and meta-analysis. Asaio J. 2017;63(2):117–122. Epub 2016/09/28. doi: 10.1097/MAT.0000000000000447. PubMed PMID:27676407.

12. Feldman D, Pamboukian SV, Teuteberg JJ, Birks E, Lietz K,Moore SA, et al. The 2013 international society for heart andlung transplantation guidelines for mechanical circulatory sup-port: executive summary. J Heart Lung Transplant. 2013;32(2):157–187. Epub 2013/01/29. doi: 10.1016/j.healun.2012.09.013.PubMed PMID: 23352391.

13. Leon MB, Smith CR, Mack M, Miller DC, Moses JW,Svensson LG, et al. Transcatheter aortic-valve implantation foraortic stenosis in patients who cannot undergo surgery. N EnglJ Med. 2010;363(17):1597–1607. Epub 2010/10/22. doi: 10.1056/NEJMoa1008232. PubMed PMID: 20961243.

14. Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG,et al. Transcatheter versus surgical aortic-valve replacement inhigh-risk patients. N Engl J Med. 2011;364(23):2187–2198. Epub2011/06/07. doi: 10.1056/NEJMoa1103510. PubMed PMID:21639811.

15. Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK,et al. Transcatheter or surgical aortic-valve replacement inintermediate-risk patients. N Engl J Med. 2016;374(17):1609–1620.Epub 2016/04/05. doi: 10.1056/NEJMoa1514616. PubMed PMID:27040324.

16. Reardon MJ, Van Mieghem NM, Popma JJ, Kleiman NS,Sondergaard L, Mumtaz M, et al. Surgical or transcatheteraortic-valve replacement in intermediate-risk patients. N EnglJ Med. 2017;376(14):1321–1331. Epub 2017/03/18. doi: 10.1056/NEJMoa1700456. PubMed PMID: 28304219.

17. Mack MJ, Leon MB, Thourani VH, Makkar R, Kodali SK,Russo M, et al. Transcatheter aortic-valve replacement with aballoon-expandable valve in low-risk patients. N Engl J Med.2019. Epub 2019/03/19. doi: 10.1056/NEJMoa1814052. PubMedPMID: 30883058. 380 1695–1705

18. Roy DA, Schaefer U, Guetta V, Hildick-Smith D, Mollmann H,Dumonteil N, et al. Transcatheter aortic valve implantation forpure severe native aortic valve regurgitation. J Am Coll Cardiol.2013;61(15):1577–1584. Epub 2013/02/26. doi: 10.1016/j.jacc.2013.01.018. PubMed PMID: 23433565.

19. Rene AG, Desai N, Wald J, Rame JE, Frogel JK, Anwaruddin S.Transfemoral transcatheter aortic valve replacement with aself-expanding valve for severe aortic regurgitation in a patient with

M. N. BELKIN ET AL.: TRANSCATHETER AORTIC VALVE REPLACEMENT STRUCTURAL HEART 111

left ventricular assist device. J Card Surg. 2017;32(11):741–745. Epub2017/11/28. doi: 10.1111/jocs.13238. PubMed PMID: 29178215.

20. Grinstein J, Kruse E, Sayer G, Fedson S, Kim GH, Jorde UP, et al.Accurate quantification methods for aortic insufficiency severity in

patients with LVAD: role of diastolic flow acceleration and systolic-to-diastolic peak velocity ratio of outflow cannula. JACC CardiovascImaging. 2016;9(6):641–651. Epub 2015/12/20. doi: 10.1016/j.jcmg.2015.06.020. PubMed PMID: 26684975.

112 M. N. BELKIN ET AL.: TRANSCATHETER AORTIC VALVE REPLACEMENT STRUCTURAL HEART