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Transcaval Access and Closure for Transcatheter Aortic Valve Replacement A Prospective Investigation Adam B. Greenbaum, MD, a Vasilis C. Babaliaros, MD, b Marcus Y. Chen, MD, c Annette M. Stine, RN, c Toby Rogers, PHD, BM BCH, c William W. ONeill, MD, a Gaetano Paone, MD, a Vinod H. Thourani, MD, b Kamran I. Muhammad, MD, d Robert A. Leonardi, MD, e Stephen Ramee, MD, f James F. Troendle, PHD, c Robert J. Lederman, MD c ABSTRACT BACKGROUND Transcaval access may enable fully percutaneous transcatheter aortic valve replacement (TAVR) without the hazards and discomfort of transthoracic (transapical or transaortic) access. OBJECTIVES The authors performed a prospective, independently adjudicated, multicenter, single-arm trial of transcaval access for TAVR in patients who were ineligible for femoral artery access and had high or prohibitive risk of complications from transthoracic access. METHODS A total of 100 patients underwent attempted percutaneous transcaval access to the abdominal aorta by electrifying a caval guidewire and advancing it into a pre-positioned aortic snare. After exchanging for a rigid guidewire, conventional TAVR was performed through transcaval introducer sheaths. Transcaval access ports were closed with nitinol cardiac occluders. A core laboratory analyzed pre-discharge and 30-day abdominal computed tomograms. The Society of Thoracic Surgeons predicted risk of mortality was 9.6 6.3%. RESULTS Transcaval access was successful in 99 of 100 patients. Device success (access and closure with a nitinol cardiac occluder without death or emergency surgical rescue) occurred 98 of 99 patients; 1 subject had closure with a covered stent. Inpatient survival was 96%, and 30-day survival was 92%. Second Valve Academic Research Consortium (VARC-2) life-threatening bleeding and modied VARC-2 major vascular complications possibly related to transcaval access were 7% and 13%, respectively. Median length of stay was 4 days (range 2 to 6 days). There were no vascular complications after discharge. CONCLUSIONS Transcaval access enabled TAVR in patients who were not good candidates for transthoracic access. Bleeding and vascular complications, using permeable nitinol cardiac occluders to close the access ports, were common but acceptable in this high-risk cohort. Transcaval access should be investigated in patients who are eligible for transthoracic access. Purpose-built closure devices are in development that may simplify the procedure and reduce bleeding. (Transcaval Access for Transcatheter Aortic Valve Replacement in People With No Good Options for Aortic Access; NCT02280824) (J Am Coll Cardiol 2017;69:51121) Published by Elsevier on behalf of the American College of Cardiology Foundation. From the a Henry Ford Hospital, Detroit, Michigan; b Emory University, Atlanta, Georgia; c National Heart, Lung, and Blood Insti- tute, National Institutes of Health, Bethesda, Maryland; d Oklahoma Heart Institute, Tulsa, Oklahoma; e Lexington Medical Center, West Columbia, South Carolina; and the f Ochsner Medical Center, New Orleans, Louisiana. This study was supported by the NHLBI Division of Intramural Research Z01-HL006040. Dr. Greenbaum is a proctor for Edwards Lifesciences and St. Jude Medical; and his employer receives research support from St. Jude Medical. Dr. Babaliaros is a researcher and consultant for Edwards Lifesciences and Abbott Vascular; and his employer receives research support from Edwards Lifesciences, Abbott Vascular, Medtronic, St. Jude Medical, and Boston Scientic. Dr. ONeill is a consultant for Edwards Lifesciences, Medtronic, St. Jude Medical, and Boston Scientic. Dr. Paone is a consultant and proctor for Edwards Lifesciences. Dr. Thourani is a consultant for Edwards Lifesciences and Abbott Vascular; and his employer receives research support from Edwards Lifesciences, Boston Sci- entic, Medtronic, St. Jude Medical, and Abbott Medical. Dr. Muhammad is a consultant for Edwards Lifesciences and Abiomed. Dr. Leonardi is a consultant for St. Jude Medical; and a paid speaker for Edwards Lifesciences. Dr. Ramee is an investigator for Listen to this manuscripts audio summary by JACC Editor-in-Chief Dr. Valentin Fuster. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 69, NO. 5, 2017 PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN 0735-1097/$36.00 http://dx.doi.org/10.1016/j.jacc.2016.10.024

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Page 1: Transcaval Access and Closure for Transcatheter Aortic ... · Transcaval Access and Closure for Transcatheter Aortic Valve Replacement A Prospective Investigation Adam B. Greenbaum,

Listen to this manuscript’s

audio summary by

JACC Editor-in-Chief

Dr. Valentin Fuster.

J O U R N A L O F T H E AM E R I C A N C O L L E G E O F C A R D I O L O G Y V O L . 6 9 , N O . 5 , 2 0 1 7

P U B L I S H E D B Y E L S E V I E R O N B E H A L F O F T H E AM E R I C A N C O L L E G E O F

C A R D I O L O G Y F O U N D A T I O N

I S S N 0 7 3 5 - 1 0 9 7 / $ 3 6 . 0 0

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Transcaval Access and Closure forTranscatheter Aortic Valve ReplacementA Prospective Investigation

Adam B. Greenbaum, MD,a Vasilis C. Babaliaros, MD,b Marcus Y. Chen, MD,c Annette M. Stine, RN,c

Toby Rogers, PHD, BM BCH,c William W. O’Neill, MD,a Gaetano Paone, MD,a Vinod H. Thourani, MD,b

Kamran I. Muhammad, MD,d Robert A. Leonardi, MD,e Stephen Ramee, MD,f James F. Troendle, PHD,c

Robert J. Lederman, MDc

ABSTRACT

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BACKGROUND Transcaval access may enable fully percutaneous transcatheter aortic valve replacement (TAVR)

without the hazards and discomfort of transthoracic (transapical or transaortic) access.

OBJECTIVES The authors performed a prospective, independently adjudicated, multicenter, single-arm trial of

transcaval access for TAVR in patients who were ineligible for femoral artery access and had high or prohibitive risk

of complications from transthoracic access.

METHODS A total of 100 patients underwent attempted percutaneous transcaval access to the abdominal aorta by

electrifying a caval guidewire and advancing it into a pre-positioned aortic snare. After exchanging for a rigid guidewire,

conventional TAVR was performed through transcaval introducer sheaths. Transcaval access ports were closed with

nitinol cardiac occluders. A core laboratory analyzed pre-discharge and 30-day abdominal computed tomograms.

The Society of Thoracic Surgeons predicted risk of mortality was 9.6 � 6.3%.

RESULTS Transcaval access was successful in 99 of 100 patients. Device success (access and closure with a nitinol

cardiac occluder without death or emergency surgical rescue) occurred 98 of 99 patients; 1 subject had closure with a

covered stent. Inpatient survival was 96%, and 30-day survival was 92%. Second Valve Academic Research Consortium

(VARC-2) life-threatening bleeding and modified VARC-2 major vascular complications possibly related to transcaval

access were 7% and 13%, respectively. Median length of stay was 4 days (range 2 to 6 days). There were no vascular

complications after discharge.

CONCLUSIONS Transcaval access enabled TAVR in patients who were not good candidates for transthoracic access.

Bleeding and vascular complications, using permeable nitinol cardiac occluders to close the access ports, were

common but acceptable in this high-risk cohort. Transcaval access should be investigated in patients who are eligible

for transthoracic access. Purpose-built closure devices are in development that may simplify the procedure and

reduce bleeding. (Transcaval Access for Transcatheter Aortic Valve Replacement in People With No Good Options

for Aortic Access; NCT02280824) (J Am Coll Cardiol 2017;69:511–21) Published by Elsevier on behalf of the

American College of Cardiology Foundation.

m the aHenry Ford Hospital, Detroit, Michigan; bEmory University, Atlanta, Georgia; cNational Heart, Lung, and Blood Insti-

e, National Institutes of Health, Bethesda, Maryland; dOklahoma Heart Institute, Tulsa, Oklahoma; eLexington Medical Center,

st Columbia, South Carolina; and the fOchsner Medical Center, New Orleans, Louisiana. This study was supported by the

LBI Division of Intramural Research Z01-HL006040. Dr. Greenbaum is a proctor for Edwards Lifesciences and St. Jude Medical;

d his employer receives research support from St. Jude Medical. Dr. Babaliaros is a researcher and consultant for Edwards

esciences and Abbott Vascular; and his employer receives research support from Edwards Lifesciences, Abbott Vascular,

dtronic, St. Jude Medical, and Boston Scientific. Dr. O’Neill is a consultant for Edwards Lifesciences, Medtronic, St. Jude

dical, and Boston Scientific. Dr. Paone is a consultant and proctor for Edwards Lifesciences. Dr. Thourani is a consultant for

wards Lifesciences and Abbott Vascular; and his employer receives research support from Edwards Lifesciences, Boston Sci-

tific, Medtronic, St. Jude Medical, and Abbott Medical. Dr. Muhammad is a consultant for Edwards Lifesciences and Abiomed.

. Leonardi is a consultant for St. Jude Medical; and a paid speaker for Edwards Lifesciences. Dr. Ramee is an investigator for

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ABBR EV I A T I ON S

AND ACRONYMS

CT = computed tomography

IDE = Investigational Device

Exemption

IVC = inferior vena cava

NHLBI = National Heart, Lung,

and Blood Institute

RPH = retroperitoneal

hematoma

STS = Society of Thoracic

Surgeons

TAVR = transcatheter aortic

valve replacement

THV = transcatheter heart

valve

VARC-2 = Second Valve

Academic Research Consor

Edwards L

baum, Rog

other autho

Manuscript

Greenbaum et al. J A C C V O L . 6 9 , N O . 5 , 2 0 1 7

Transcaval TAVR Prospective Trial F E B R U A R Y 7 , 2 0 1 7 : 5 1 1 – 2 1

512

T ranscatheter aortic valve implanta-tion (TAVR) avoids the morbidityand mortality of surgical aortic valve

replacement in high- and intermediate-riskpatients (1–6). Transthoracic (transapicaland transaortic) access is inferior comparedwith femoral artery access (6), perhaps inpart because of the clinical features preclud-ing femoral artery access. Discomfort andmorbidity are more pronounced in transtho-racic access for TAVR, probably because ofthe invasiveness and pulmonary insults. Analternative transfemoral access approach toTAVR might be desirable in these patientsto reduce the hazards and discomfortof transthoracic access and because of thesuperior operator ergonomics.

We developed a technique of transfemoral

venous access for retrograde TAVR by entering theabdominal aorta through the adjoining inferior venacava (IVC), now called transcaval access (7) (CentralIllustration). Animals tolerate the resulting acuteaorto-caval fistula even without repair, because theretroperitoneal space appears to pressurize and causeaortic blood to return immediately through the cor-responding hole in the vena cava (Figure 1). Patientstolerate transcaval access after nitinol cardiacoccluders are implanted to close the aortic port.Transcaval access and closure were uniformly suc-cessful in the first 19 patients, all of whom had nogood TAVR access options (8).

tium

SEE PAGE 522

We have refined the technique of transcaval accessand closure (9), and we tested the early multicenterexperience in a single-arm prospective Investiga-tional Device Exemption (IDE) trial in patientsdeemed to have high or prohibitive risk of complica-tions from transthoracic access for TAVR. This studydescribes 30-day outcomes in 100 patients.

METHODS

PATIENTS AND STUDY DESIGN. The study evaluatedsuccess and complications of transcaval TAVRaccess and closure with a nitinol cardiac occluderdevice. It was designed as a prospective, open-label,multicenter, single-arm study with on-site

ifesciences and St. Jude Medical; and has received honoraria fro

ers, and Lederman are co-inventors of devices, not tested in thi

rs have reported that they have no relationships relevant to the

received October 8, 2016; revised manuscript received October 2

monitoring, independent endpoint adjudication, andcentral core laboratory analysis of follow-up images(NCT02280824).

Patients were eligible to participate if: 1) they hadsevere symptomatic native aortic valve stenosis orbioprosthetic aortic valve failure for which TAVR wasindicated; 2) extreme risk or inoperability for conven-tional femoral artery, transapical, or transaortic accessas determined by the institutional multidisciplinaryheart team; and 3) anatomic suitability for transcavalaccess according to a baseline computed tomographic(CT) scan analyzed by the National Heart, Lung, andBlood Institute (NHLBI) core laboratory. These arefurther detailed in the Online Appendix. Screeningdetails on ineligible candidates were not collected.

The U.S. Food and Drug Administration grantedIDE for this sponsor-investigator study, which hadinstitutional research board approval from all 20participating sites and NHLBI. All patients providedwritten consent. The NHLBI Data Safety MonitoringBoard provided oversight, and the Medstar Heart andVascular Institute Clinical Events Committee inde-pendently adjudicated the pre-specified endpoints.Sites received on-site proctorship by the principalinvestigator and/or sponsor.

The IDE was sponsored by the senior author (RJL)on behalf of NHLBI, which was the data coordinationcenter. Sites participated without NHLBI funding.The manufacturer of the IDE test device (Amplatzernitinol occluders, St. Jude Medical, St. Paul, Minne-sota) allowed the Food and Drug Administration tocross-reference the device master file for the IDE, butdid not otherwise participate in the study. Patientswere concurrently enrolled into the Society ofThoracic Surgeons/American College of CardiologyTranscatheter Valve Therapies (TVT) Registry (10).

TECHNIQUE OF TRANSCAVAL ACCESS AND

CLOSURE. The technique was previously described(8,9). Briefly, the procedure was planned from thebaseline TAVR CT (11,12) to identify a calcium-freetarget on the right aortic wall that allowed safe pas-sage of the TAVR sheath from the IVC to the abdominalaorta. The trajectory of the sheath had to be free ofinterposed obstacles (bowel), and the area of aorticentry had to be away from important arterial branches,which allowed for provisional covered stent bailout ifnecessary. After heparin anticoagulation, a loop snare

m Edwards Lifesciences and Medtronic. Drs. Green-

s protocol, intended to close transcaval access. The

contents of this paper to disclose.

1, 2016, accepted October 24, 2016.

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CENTRAL ILLUSTRATION Transcaval Access Technique for TAVR

Greenbaum, A.B. et al. J Am Coll Cardiol. 2017;69(5):511–21.

(A) Transcaval access is obtained over an electrified guidewire directed from the inferior vena cava toward a snare in the abdominal aorta. (B) After

delivering a microcatheter to exchange for a stiff guidewire, (C) the transcatheter heart valve introducer sheath is advanced from the femoral vein into

the abdominal aorta for conventional transfemoral retrograde transcatheter aortic valve replacement (TAVR). (D) The aorto-caval access site is closed with

a nitinol cardiac occluder. Courtesy of A. Hoofring, NIH Medical Arts Branch.

J A C C V O L . 6 9 , N O . 5 , 2 0 1 7 Greenbaum et al.F E B R U A R Y 7 , 2 0 1 7 : 5 1 1 – 2 1 Transcaval TAVR Prospective Trial

513

was placed into the aorta to serve as a target. A coaxialcrossing system consisting of a 0.014-inch � 300-cmcoronary guidewire (Confienza Pro 12 or Astato XS20,Asahi, Abbott, Santa Clara, California) inside a 0.035-inch � 145-cm locking wire convertor (Piggyback,Vascular Solutions, Minneapolis, Minnesota), inside abraided 0.035-inch�90-cmmicrocatheter, inside a 6-F

to 7-F renal-length IMA or RDC1 guiding catheter(Figure 2) was positioned into the cava. It was aimedtoward the aortic snare, and electrified using amonopolar electrosurgery pencil at 50 W during briefguidewire advancement across the vascular walls.Once the 0.014-inch guidewire was snared, counter-traction allowed the wire convertor and 0.035-inch

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FIGURE 1 Proposed Mechanism of Hemodynamic Stability After Transcaval Access

Using Permeable Nitinol Occluder Devices

IVC10 mm Hg Retroperitoneum

20 mm Hg Aorta100 mm Hg

Higher pressure in the relatively confined retroperitoneal space exceeds venous pressure

(inset) and causes aortic blood to return to the venous circulation through a nearby hole

in the inferior vena cava (IVC) (inset). The result is aortocaval fistula rather than

hemodynamic collapse. Courtesy of A. Hoofring, NIH Medical Arts Branch.

Greenbaum et al. J A C C V O L . 6 9 , N O . 5 , 2 0 1 7

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514

microcatheter to be advanced successively acrossthe aortic wall and then exchanged for a rigid 0.035-inch � 260-cm guidewire (Lunderquist, Cook Medi-cal, Bloomington, Indiana). The TAVR introducersheath (13) (Retroflex 3 or eSheath, Edwards Life-sciences, Irvine California, or extra-large Check-Flo,Cook) for Edwards Sapien valves or large Check-Flo18-F � 40 cm (Cook) for Corevalve (Medtronic,

FIGURE 2 Crossing Equipment

(A) Coaxial crossing system consisting of (1) 0.014-inch guidewire inside

microcatheter, inside of a (4) 55-cm guiding catheter. (B) An electrosur

guidewire (6) using a hemostatic forceps (7).

Dublin, Ireland) was then introduced from thefemoral vein into the aortic lumen over the rigidguidewire. Pre-dilatation with a noncompliantcoronary dilatation balloon (2 to 3 mm � 20 cm)was performed when necessary to advance themicrocatheter. Retrograde TAVR was performedusing the standard transfemoral technique.

To close the access port after TAVR, heparin anti-coagulation was fully reversed with protamine, and anitinol cardiac occluder (Amplatzer Duct Occluder orAmplatzer Ventricular Septal Defect Occluder, St.Jude Medical) was positioned in the aorta through theTAVR introducer sheath alongside a 0.014-inch buddyguidewire, rotated sideways using a deflectable cath-eter (Agilis NxT SML curl, St. Jude Medical), anddeployed along the right aortic wall. Pigtail aorticangiography guided the occluder device positioning.Aortocaval fistulas were accepted unless they causedheart failure from shunting. If retroperitoneal bleedingwas evident, adjunctive balloon aortic tamponade orself-expanding covered stents (typically iliac limb ex-tenders, Endologix or Trivascular, Irvine, California)were deployed at physician discretion. Post-procedureantiplatelet and anticoagulation medications wereadministered according to local routine.

DATA ANALYSIS. Clinical outcomes were enteredinto electronic case report forms and independentlymonitored. Follow-up CT scans that were contrastenhanced when renal function permitted were ob-tained before discharge and at 30 days. Angiogramsand CT scans were analyzed in central NHLBI corelaboratories. An independent clinical events adjudi-cation committee classified all deaths, bleeding,

of a (2) Piggyback 0.035-inch wire convertor inside of a (3) braided

gery pencil (5) is connected to the backend of the 0.014-inch

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FIGURE 3 Representative Transcaval TAVR Procedure

(A to E) A suitable target (yellow arrow) is identified on computed tomography (CT) and displaced in (C) axial reconstruction to show the crossing point (yellow arrow),

(D) sagittal reconstruction to show the lumbar level, and (E) coronal thick-slab projection to simulate fluoroscopy. (F) Under fluoroscopy, the transvenous crossing

catheter is aligned with the aortic snare in a lateral projection; (G) the guidewire is electrified during advancement into the aorta and (H) then snared and exchanged for

a stiff guidewire. (I) The transcatheter heart valve (THV) sheath is advanced from the femoral vein into the aorta. (J to L) After transcatheter aortic valve replacement

(TAVR), a nitinol cardiac occluder device is positioned across the aortic wall. (M) In this case, completion angiography shows complete occlusion of the aorto-caval

fistula. (N and O) Pre-discharge CT shows the device in position with a small retroperitoneal hematoma and an occluded tract. An alternative target is depicted with a

purple arrow.

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TABLE 1 Baseline Characteristics (N ¼ 100)

Age, yrs 79.5 (73.0, 85.0)

Female 58

Race

White 84

Black 9

Other 7

Left ventricular ejection fraction, % 52.8 � 15.6

CHF (NYHA functional class) 3.2 � 0.6

Right ventricular enlargement or dysfunction 24

Coronary artery disease 89

Previous cardiac surgery 44

End-stage renal disease or dialysis 10

eGFR, ml/min/1.73 m2 52.6 � 23.6

NT–pro-BNP/BNP, pg/ml 421 (183, 1,070)

Long-term anticoagulation 42

STS predicted risk of mortality, % 9.6 � 6.3

Euroscore II predicted risk of mortality, % 10.9 � 9.8

TVT risk score (15), % 9.2 � 7.2

Site-reported reasons unsuitable for conventional access

Clinical 86/100

Frailty 54

Advanced pulmonary disease 39

Advanced age and predicted mortality 44

Immunosuppression 8

Morbid obesity 7

Technical 91/100

Factors impeding transaortic access: porcelain aorta,threatened grafts, previous chest radiation, previoussternal wound infection, inadequate working length

53

Factors impeding transapical access: failed previoustransapical, chest radiation, chest wound infection,fatty myocardium

11

Inadequate ilio-femoral artery diameter irrespective ofcalcification or tortuosity

82

Values are n (25th, 75th percentile), n, or mean � SD.

CHF ¼ congestive heart failure; eGFR ¼ estimated glomerular filtration rate; NYHA ¼ New YorkHeart Association; NT–pro-BNP ¼ N-terminal pro-brain natriuretic peptide; STS ¼ Society ofThoracic Surgeons; TVT ¼ Transcatheter Valve Therapy Registry.

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516

vascular complications, major adverse cardiovascularevents, and their relatedness to transcaval access andclosure according to a modification of the SecondValve Academic Research Consortium (VARC-2) (14)(Online Appendix). NHLBI has custody of all data;the sponsor and the principal investigator areresponsible for data integrity.

The primary endpoint was device success, whichwas defined as successful transcaval access anddeployment of a closure device without death oremergency open abdominal surgery. Data are re-ported as mean � SD or median (25th, 75th percentile)as appropriate. Continuous and integer data werecompared using Student t test or Fisher exact test,respectively. To identify predictors of bleeding orvascular complications, we assessed associationseparately for each potential predictor (age, sex,closure device/sheath ratio, sheath/aorta ratio, aortic

diameter, fistula patency, balloon aortic tamponade,covered stent, transcaval procedure volume), andeach discrete outcome by fitting a proportional-oddscumulative-logit model in SAS version 9.4 (SASInstitute, Cary, North Carolina). Multivariable modelswere formed using a backwards stepwise selection ofclinical and procedural factors (excluding thosebelieved to be consequents of bleeding) until onlyfactors with p < 0.20 remained. Effects of transcavalexperience were assessed by creating a dichotomousvariable indicating the 2 sites with the highest-enrollment.

RESULTS

ENROLLMENT. We enrolled 100 patients who under-went attempted transcaval TAVR at 17 of 20 sitesbetween July 2014 and June 2016. Thirty-day follow-up data were obtained for all patients. Sites per-formed a median of 2 (25th, 75th percentile: 0, 4)transcaval procedures before this study was initiated.

PROCEDURE OUTCOMES. Transcaval access andclosure were successful in 99 of 100 attempts. Atypical procedure is depicted in Figure 3. Baselinecharacteristics, including predictors of transthoracicaccess complications, are shown in Table 1. Procedurecharacteristics are shown in Table 2. In 1 subject, theguidewire failed to cross, and the operator subse-quently performed transfemoral artery TAVR that wascomplicated by iliac artery rupture. Device success,the primary endpoint of the study, occurred in 98 of100 patients. This included the failure to cross andanother patient in whom the operator chose primaryclosure using a covered aortic stent instead of repo-sitioning a fully withdrawn nitinol occluder. All pa-tients survived the immediate TAVR procedure, andnone died as a direct consequence of transcaval ac-cess and closure, nor did any undergo emergencysurgical rescue of the transcaval access site. TAVRcomplications included: 1 case of transcatheter heartvalve (THV)-related coronary obstruction that wasultimately fatal; 1 case of aortic annular hematomamanaged conservatively and successfully; no THVembolization; 16 new permanent pacemakers; and nocases of endocarditis during the 30-day landmarkanalysis.

Inpatient and 1-month follow-up data are shown inTable 3. Four patients died before hospital discharge,2 each of cardiovascular and noncardiovascular cau-ses. Thirty-day landmark survival was 92%. Sevendeaths were adjudicated as cardiovascular and 1 asnoncardiovascular. Specific causes of death are elab-orated in the Online Appendix.

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TABLE 2 Procedure Characteristics (N ¼ 100)

”Valve-in-valve” TAVR 6

Crossing duration, from snare tointroducer sheath, min

21.1 � 17.5

Need for tract balloon dilatation afterinitial guidewire crossing

40

Valve type Edwards Sapien XT (n ¼ 23)Edwards Sapien 3 (n ¼ 57)

Medtronic Corevalve (n ¼ 11)Medtronic Corevalve Evolut R (n ¼ 9)

Valve size nominal, mm 20 (n¼ 3)23 (n ¼ 37)26 (n ¼ 41)29 (n ¼ 19)

Sheath model Edwards Retroflex 3 (n ¼ 6)Edwards eSheath (n ¼ 73)

Cook Large Check-Flo (n ¼ 13)Cook Extra-Large Check-Flo (n ¼ 8)

Sheath outer diameter, mm 8.0 � 0.7

TAVR success* 100%*

Closure duration, from introducingdevice to completion angiogram(min)

14.1 � 9.5

Closure device ADO (n ¼ 58)VSD (n ¼ 40)None (n ¼ 2)

Final closure device size Amplatzer Duct Occluder (n ¼ 58)8/6 mm (n ¼ 7); 10/8 mm (n ¼ 51)

Amplatzer Muscular VSD Occluder (n ¼ 40)6 mm (n ¼ 10); 8 mm (n ¼ 27); 10 mm (n ¼ 3)

Covered stent only (n ¼ 1)

Angiographic closure score (8) 1.0 � 0.8

Adjunctive balloon aortic tamponade 17

Total contrast volume (ml) 166 � 87

Anesthesia technique General anesthesia with endotracheal intubation(n ¼ 84) (52 [62%] extubated on-table); moderate

sedation (n ¼ 16)

*All transcatheter aortic valve replacement (TAVR) procedures were successful; however, 1 of 100 was performedvia a femoral artery route, complicated by iliac artery rupture.

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Bleeding and vascular complications are listed inTable 4. Transcaval-related bleeding was adjudicatedas VARC-2 major or life-threatening in 12 of 99 pa-tients. Overall, 35 patients received a median of 2.0 U(25th, 75th percentile: 2.0, 4.0 U) of red cell trans-fusions during their transcaval TAVR admission.Transcaval-related vascular complications wereadjudicated as modified VARC-2 major in 13 of 99 pa-tients, typically because of a retroperitoneal hema-toma detected on mandatory CT scan combined with adecrease in hemoglobin. Covered stents were placedin 8 patients after transcaval access and closure, allbut 1 during the same procedure. The indication wasongoing extravasation after deploying the transcavalclosure device in the 1 patient who received apixabanduring the procedure, intolerable left-to-right shuntin 2 patients that manifested as hemodynamic insta-bility and deterioration of right ventricular function,and 1 stent used for primary closure of the transcavalaccess site after complete withdrawal of the nitinoloccluder device. The indications for covered stentplacement were less clear in the remaining 4 patients.One subject had aortic root hematoma, and the oper-ator placed a covered aortic stent to reduce diagnosticambiguity should hemodynamic instability ensue.One subject had unexplained hypotension that did notimprove by covered stent use; in retrospect, the hy-potension was attributed to anesthesia medications.One subject was taken back to the catheter laboratoryin the evening after the transcaval procedure for hy-potension and evident retroperitoneal hematoma,and a covered stent was placed out of caution,although there was no extravasation. One subject hada covered stent placed to treat a pre-existing aorticdissection at the transcaval access site, which waspre-planned by the operator. Post hoc multivariateanalysis of clinical and procedural characteristicsidentified predictors of bleeding (Online Appendix),including the small closure device/sheath diameterratio, baseline hemodialysis, older age, larger aortas,and sites with lower enrollment. Post hoc predictors ofvascular complications included larger sheath/aortadiameter ratio and sites with lower enrollment. Theaorto-caval fistula was occluded immediately aftertranscaval TAVR in 36 of 99 (36%) patients. Among theevaluable mandatory CT scans (Table 5), the fistulawas occluded in 38 of 72 (53%) patients at hospitaldischarge and 48 of 66 (72%) patients at 30 days. Sixty-four of 99 (64%) patients had tracts that wereoccluded by 30 days according to angiography find-ings combined with CT.

Retroperitoneal hematomas (Table 5) were foundby the core laboratory in 24% of patients beforedischarge and in 5% of patients after 30 days. Most

were graded small or moderate. There were novascular complications after discharge.

No patient had a complication related to thetranscaval closure device or closure site, or aorticpseudoaneurysm, after hospital discharge.

There were 2 TAVR-related myocardial infarctions,1 of which was fatal. There were 5 TAVR-relatedischemic strokes. Three patients developed acutetubular necrosis classified as acute kidney indexscores of 3, including 2 who required hemodialysis.There were no cases of hemolytic anemia or infectednitinol occluder devices. Five patients had nadirplatelet counts <50 � 109/ml, 4 of whom had a patentaortocaval fistula on the final angiogram, and none ofwhom had evident sequelae.

There were fewer complications in one-half of thepatients treated at centers with more transcavalexperience, including VARC-2 30-day safety events(17% vs. 36%; p ¼ 0.03), covered stents (6% vs. 11%;p ¼ 0.32), major or life-threatening bleeding (13%vs. 28%; p ¼ 0.01), major vascular complications

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TABLE 3 Outcomes Through 30 Days (N ¼ 100)

Death within 30 days 7 Cardiovascular1 Noncardiovascular

Stroke 5 Ischemic

Myocardial infarction 2 Peri-procedural

Contrast nephropathy requiring dialysis 2

Acute kidney injury classification Grade 0 (n ¼ 87)Grade 1 (n ¼ 9)Grade 2 (n ¼ 0)Grade 3 (n ¼ 3)

Thrombocytopenia <50 � 103 / ml 5 (4 with patent fistula)

Non-access-related bleeding (e.g., gastrointestinal) 15

Transfusion during TAVR/after TAVR/during or after TAVR 14/30/35

Transfusion units among those transfused (median) (n ¼ 35/100) 2.0 (2.0, 4.0)

Follow-up CT scan before discharge 87

Post-TAVR length of stay (days), median (quartiles) 4 (2–6)

Post-TAVR intensive care unit length of stay (days), median (quartiles) 1 (1–3)

VARC-2 composite early safety* 75

*Second Valve Academic Research Consortium (VARC-2) composite early safety is 30-day freedom frommortality, stroke, life-threatening bleeding, acute kidney injury stage 2 or 3, coronary artery obstructionrequiring intervention, major vascular complication, or valve-related dysfunction requiring repeat procedure.

CT ¼ computed tomography; TAVR ¼ transcatheter aortic valve replacement.

TABLE 4 Key Complications

New Transcaval-RelatedCount

(n ¼ 99) Details

Bleeding

Life-threatening

Yes 6 5 RPH (large [n ¼ 2]; moderate [n ¼ 2];small [n ¼ 1])

1 Covered aortic and iliac stents, no RPH

Indeterminate 1 1 Thoracic aortic dissection fromCorevalve Evolut R

No 5 2 Pericardial tamponade1 Femoral artery closure device failure1 Epistaxis related to anesthesia care1 GI hemorrhage

Major Yes 5 5 RPH (4 moderate, 1 small) including 1concurrent GI and jugular access hemorrhage

No 1

Minor Yes 11

No 8

None — 62

Vascular complications

Major Yes 12 9 RPH (any size) þ major or life-threateningbleeding

1 Covered stent for extravasation1 Primary closure with covered aortic and

femoral artery stents1 Noncovered aortic stent for local dissection

Indeterminate 1 1 Thoracic aortic dissection from CorevalveEvolut R

No 6 2 Pericardial tamponade1 Aortic root hematoma1 Lower extremity revascularization1 Femoral artery closure device failure1 Other

Minor Yes 13

No 4

None — 63

Bleeding and vascular complications are classified as the most serious event for each patient. One patient isexcluded because of unsuccessful transcaval access.

GI ¼ gastrointestinal; RPH ¼ retroperitoneal hematoma.

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(11% vs. 28%; p ¼ 0.03), and acute kidney index $1(7% vs. 15%; p ¼ 0.22), although some differences didnot meet statistical significance. There was no dif-ference in outcomes between the first and second halfof patients enrolled.

DISCUSSION

Transcaval access and closure for TAVR were success-ful in a cohort of patients without good conventionalaccess options. This is remarkable, because mostparticipating centers had limited previous transcavalexperience, we used a permeable closure device, andpatients had extensive comorbidities. The observed30-day mortality rate was 8%, although no patientdied or required surgical bailout as a direct conse-quence of transcaval access. Adjudicated bleeding andvascular complications were common. From a patient-centered outcome perspective, the primary observedmorbidity (blood transfusions) compared favorablywith the morbidity of surgical transthoracic access.

The included patients were not eligible for femoralartery access and were deemed poorly suited or inel-igible for transthoracic access. Seventy-seven percentreceived contemporary low-profile THV devices.Eligibility for transthoracic access was a subjectiveclinical determination made by the local multidisci-plinary heart team, including the cardiac surgeons.The included patients had a high Society of ThoracicSurgeons (STS) predicted risk of mortality (9.7 � 6.3%)and a heavy burden of comorbidities. We speculatedthat patients with fewer comorbidities, who might besuitable for transthoracic access, might experiencefewer complications from transcaval access.

Despite fears of catastrophic hemorrhage, trans-caval access appeared to be well-tolerated. We infer-red that the retroperitoneal space surrounding theaortic entry site pressurizes during and after closure,and that aortic bleeding decompresses into thenearby venous hole because retroperitoneal pressureexceeds venous pressure (Figure 1). In a small numberof patients, a transiently unrepaired aorto-caval fis-tula was well-tolerated after pull-through of a closuredevice (Figure 4), or during replacement of theintroducer sheath or dilator. Even after deviceclosure, asymptomatic residual aorto-caval fistulaepersisted in two-thirds of patients before dischargeand one-third after the first month.

Life-threatening (also known as “disabling”)bleeding occurred in 12% of high or prohibitive riskpatients after transcaval TAVR in this study (meanSTS score 9.6), compared with 22.6% of intermediate-risk patients after transthoracic TAVR and 6.7% ofpatients after transfemoral TAVR using the Sapien 3

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TABLE 5 Computed Tomographic Findings

Aorto-caval fistula

Timepoint Occluded Patent Indeterminate(noncontrast orpoor contrast

timing)

Pre-discharge (n ¼ 87) 38 34 15

30 day (n ¼ 76) 48 18 10

Retroperitoneal hematoma

Timepoint None Small Moderate Large

Pre-discharge (n ¼ 88) 67 (76) 12 (14) 7 (8) 2 (2)

30 days (n ¼ 76) 72 (95) 3 (4) 0 1 (1)

Values are n or n (%).

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THV in the PARTNER-II trial (mean STS score 5.8) (6).In the other major pivotal TAVR trials for which dataare available according to type of access, non-transfemoral access (transapical or transaortic) wasassociated with major vascular complication rates of3.8% to 5.9% and life-threatening or major bleedingrates of 8.7% to 22.6% (3,6,16). In large, non-adjudicated single-center and national TAVR regis-tries, the rate of life-threatening and major bleedingwith non-transfemoral access ranged from 3.6% to37.3%, the rate of transfusion ranged from 8.9% to25.4%, and the rate of major vascular complicationsranged from 0.6% to 2.4% (17–22).

FIGURE 4 Unconstrained Aorto-Caval Shunt After Inadvertent Pull-

(A) This angiogram was performed while preparing a new closure device

(B) A fistula persists on the completion angiogram after a closure device w

hematoma, and the fistula is reduced but persistent. (E and F) It is occl

Despite a paucity of randomized data on alternateextrathoracic access approaches such as transcarotid,subclavian, or transaxillary, single-center experiencesuggested these approaches compared favorably witha transthoracic approach, with acceptable rates ofbleeding and vascular access complications (17,23,24).However, none of these studies had systematicfollow-up imaging or independent adjudication.Compared with carotid, subclavian, and axillary ar-tery access, transcaval access may provide: 1) superioroperator ergonomics because the operators work fromthe standard right groin puncture site; 2) less tortuoussheath trajectory; 3) less risk of brachial plexus injury;and 4) no surgical dissection. All of these extra-thoracic access methods appear to work well.

In this study, adjudicators classified transcaval-related vascular and bleeding complications accord-ing to modified VARC-2 standards (14). Because weobtained CT scans systematically before discharge,and because blood transfusions were common (35%),VARC-2 classified vascular complications as “major”even when patients had otherwise uneventful clinicalcourses. For example, a patient who had a smallretroperitoneal blood collection on CT and who had a2-U blood transfusion without an overt source ofbleeding would be classified as having majorbleeding, yet they would also have been classified as

Through of a Closure Device

. The blood pressure was not changed. The arrow points to the unrepaired aorto-caval fistula.

as implanted. (C and D) On pre-discharge computed tomography, there is no retroperitoneal

uded on follow-up computed tomography.

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PERSPECTIVES

COMPETENCY IN PATIENT CARE AND

PROCEDURAL SKILLS: In candidates for TAVR who

are ineligible for transfemoral access and at high risk of

complications with transapical or transaortic access,

transcaval access may be a feasible alternative.

TRANSLATIONAL OUTLOOK: Further studies are

needed to assess the safety and efficacy of closure

devices for use in patients undergoing transcaval access

for TAVR and to compare the transcaval approach with

direct transaortic approaches.

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having no bleeding had there not been systematicfollow-up imaging.

Covered stents were used in 8% of patients, lessthan one-half for extravasation or an intolerableshunt through the permeable nitinol occluderdevices, and none for catastrophic aortic disruptionor hemodynamic collapse. Covered stents wereconsidered a failure only because this study wasdesigned to evaluate the specific permeable nitinolcardiac occluder devices in the closure of transcavalaccess ports. In contrast, in clinical practice, a provi-sional strategy of nitinol occluder implantation andbailout covered stenting seems prudent and practical.

Outcomes after transcaval access have improvedsince the first human experience study (8). Bleedingand vascular complications have declined because oftechnique refinements, such as complete reversal ofheparin anticoagulation before closure, consistentimplantation of slightly oversized closure devices,use of a deflectable sheath to rotate the closure devicehorizontally during deployment, and liberal use ofballoon aortic tamponade, although the closuredevices have not changed. In this prospective trial,centers with more transcaval experience trendedtoward fewer complications. Outcomes mightimprove further using a purpose-built closure devicethat is immediately hemostatic.

STUDY LIMITATIONS. Limitations of this investiga-tion included the absence of a control group, the in-clusion of patients without other good options whohad expected high morbidity and mortality notnecessarily reflected in their risk score, use of apermeable nitinol occlude device, the participation ofsites with little or no previous experience, the largeproportion (18%) of patients who had missing follow-up CT, and limited data collection, including cost,quality of life, and frailty. Some countervailingstrengths included independent clinical event adju-dication and data monitoring, and careful centralizedanalysis of follow-up CT. Compared with femoralartery access, transcaval procedures imparted addi-tional logistical complexity of planning, crossing, andclosure. The extra expense of closure devices might

possibly be offset by reduced morbidity and length ofstay compared with transthoracic access.

Transcaval access might prove valuable for otherclinical applications. It was used successfully as partof thoracic endovascular aneurysm repair (25) and tointroduce 5.0 L percutaneous left ventricular assistdevices (Impella, Abiomed, Danvers, Massachusetts)(26). The transcaval approach might allow trans-catheter implantation of other large devices, forexample, to treat aortic regurgitation.

CONCLUSIONS

Transcaval access is a realistic alternative for TAVR.These data supported cautious clinical adoption inpatients without good access options and comparisonagainst more established alternative access routes inlower risk patients. Outcomes and applicability mightimprove with more experience and using a purpose-built, impermeable closure device to achieve imme-diate hemostasis.

ADDRESS FOR CORRESPONDENCE: Dr. Robert J.Lederman, Cardiovascular and Pulmonary Branch,Division of Intramural Research, National Heart,Lung, and Blood Institute, National Institutes ofHealth, Building 10, Room 2c713, MSC 1538, Bethesda,Maryland 20892-1538. E-mail: [email protected].

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KEY WORDS caval-aortic access,nontransfemoral access, structural heartdisease, transcatheter aortic valvereplacement, transcaval, vascular access

APPENDIX For an expanded Methodssection, please see the online versionof this article.