early single-site experience with transcatheter tricuspid...

J A C C : C A R D I O V A S C U L A R I M A G I N G V O L . 1 2 , N O . 3 , 2 0 1 9

ª 2 0 1 9 B Y T H E A M 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

P U B L I S H E D B Y E L S E V I E R

ORIGINAL RESEARCH

Early Single-Site Experience WithTranscatheter TricuspidValve Replacement
Rebecca T. Hahn, MD,a Isaac George, MD,a Susheel K. Kodali, MD,a Tamim Nazif, MD,a Omar K. Khalique, MD,a
Deniz Akkoc, BA,a Alex Kantor, BA,a Torsten P. Vahl, MD,a Amisha Patel, MD,a Elliott Elias, MD,a Vivian Ng, MD,a

Roberto Spina, MD,a Krzysztof Bartus, MD,b Poonam Velagapudi, MD,b Isaac Wu, MD,a Martin Leon, MD,a

Vinayak Bapat, MDa

ABSTRACT

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OBJECTIVES This study presents a single-site experience of 5 patients with severe tricuspid regurgitation (TR) who

underwent implantation of a novel transcatheter tricuspid valve replacement device.

BACKGROUND Functional TR is the most common etiology of severe TR in the developed world and is associated with

unfavorable clinical outcomes. Although numerous transcatheter repair devices are currently in early clinical trials, most

result in incomplete degrees of TR reduction and functional improvement.

METHODS Transcatheter tricuspid valve replacement was performed in 5 patients with compassionate use of the novel

GATE System. All patients had symptomatic, massive and/or torrential TR at baseline. All patients had computed

tomography, transthoracic and transesophageal echocardiographic assessment of the tricuspid valve and right heart

anatomy. All patients had a surgical transatrial approach performed with valve implantation guided by fluoroscopy and

intraprocedural transesophageal echocardiography.

RESULTS Baseline characteristics of the patients showed a substantial burden of comorbidities. All patients had suc-

cessful implantation of the transcatheter valve, with significant reduction of TR to #2þ. Baseline poor right ventricular

(RV) function measured by global longitudinal strain and RV change in pressure divided by change in time were associated

with post-implantation RV failure and poor clinical outcomes in this small group. Four of the 5 patients were followed

for 3 to 6 months following the initial implantation and showed evidence of RV remodeling, increased cardiac output,

and reduction in New York Heart Association functional class.

CONCLUSIONS Implantation of a first-generation TTVR device was technically feasible in patients withmore than severe

TR. Transcatheter tricuspid valve replacement was associated with RV remodeling, increased cardiac output, and

improvement in New York Heart Association functional class in most patients. Further studies are needed to refine

patient population selection for this device and to determine long-term outcomes. (J AmColl Cardiol Img 2019;12:416–29)

© 2019 by the American College of Cardiology Foundation.

N 1936-878X/$36.00 https://doi.org/10.1016/j.jcmg.2018.08.034

m the aColumbia University Medical Center/NewYork Presbyterian Hospital, New York, New York; and the bDepartment of

rdiovascular Surgery and Transplantology, Jagiellonian University Medical College, John Paul II Hospital, Krakow, Poland.

s. Hahn and Bartus are consultants for NaviGATE. Dr. Kodali has been a member of the advisory board for Abbott Vascular,

trace Medical, Dura Biotech, and Thubrikar Aortic Valve; has been a consultant for Merrill Lifesciences and Claret Medical;

d owns equity in Dura Biotech, Thubrikar Aortic Valve, and Biotrace Medical. Dr. Nazif has been a consultant for Edwards

esciences, Medtronic, and Boston Scientific. Dr. Khalique has been a member of the Speakers Bureau for Edwards

esciences. Dr. Bapat has been consultant for Medtronic and Edward Lifesciences. All other authors have reported that they

ve no relationships relevant to the contents of this paper to disclose.

nuscript received June 22, 2018; revised manuscript received August 1, 2018, accepted August 1, 2018.

https://doi.org/10.1016/j.jcmg.2018.08.034

http://crossmark.crossref.org/dialog/?doi=10.1016/j.jcmg.2018.08.034&domain=pdf

AB BR E V I A T I O N S

AND ACRONYM S

2D/3D = 2-/3-dimensional

CT = computed tomography

dP/dT = change in pressure

divided by change in time

RA = right atrium

RV = right ventricular

TA = tricuspid annulus

TEE = transesophageal

echocardiography

TAPSE = tricuspid annular

plane systolic excursion

TTE = transthoracic

echocardiography

TR = tricuspid regurgitation

TTVR = transcatheter tricuspid

replacement

J A C C : C A R D I O V A S C U L A R I M A G I N G , V O L . 1 2 , N O . 3 , 2 0 1 9 Hahn et al.M A R C H 2 0 1 9 : 4 1 6 – 2 9 Transcatheter Tricuspid Valve

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I nterest in functional or secondary tricuspidregurgitation (TR) has increased in recent years,with recognition of the progressive nature of

the disease (1,2) and its affect on mortality (3–5).Analysis of national trends of surgery for TR hasshown that between 2004 and 2013, valve replace-ment was performed in 59.2% of patients, whereastricuspid valve repair was performed in 40.8% (6).Although the rates of repair procedures is increasing,recurrence of significant TR following repair has beenreported to be as high as 42% by 5 years, with a 14%recurrence of moderate or severe TR just 1 weekfollowing repair (7), which suggests that annularrepair may be inadequate for certain patients.

Due to high surgical mortality for isolated tricuspidvalve disease (6,8), a number of transcatheter annularrepair devices have been developed (9). Early reportsof these devices have shown variable reduction in TR(10–14). This is the first report of a single-site series ofpatients who received a novel transcatheter tricuspidvalve replacement (TTVR) device.

SEE PAGE 430

METHODS

DEVICE DESCRIPTION. The GATE System (NaviGateCardiac Structures, Inc., Lake Forest, California) iscomposed of an atrioventricular valved stent, a de-livery system, a compression loading system, and anintroducer sheath. The valve stent is nitinol alloywith a conical shape (Figure 1A) and is available in 4sizes (40 to 52 mm diameter) intended for nativetissue tricuspid annular diameters of 36 to 52 mm(Table 1). Twelve right ventricular (RV) tines grasp thetricuspid leaflets from the RV side. There are 12 rightatrial (RA) winglets perpendicular to the conical stentand covered by a microfiber polyester cloth designedto provide a seal. The 3 leaflets and the skirt are madeof treated equine pericardium. The delivery systemconsists of a tip-deflecting catheter designed to gothrough a 42F introducer sheath (Figure 1B and 1C).

PRE-PROCEDURAL IMAGING. Transthoracic echocardiography.Comprehensive transthoracic echocardiography (TTE)was performed before the procedure in each case.Functional TR is believed to be a disease determinedby not only tricuspid valve and/or annular sizeand morphology, but also by RV size and function,interventricular septal displacement, and pulmonaryartery pressures (15). Thus, multiple measures of RVsize and function were performed according to theAmerican Society of Echocardiography guidelines (16),including RV basal and mid-dimensions (4-chamberview), tricuspid annular plane systolic excursion(TAPSE), fractional area change, and systolic tissue

Doppler velocity. RV change in pressuredivided by the change in time (dP/dT) repre-sents the instantaneous rate of RV pressurerise during early systole and was measuredfrom any view that images the color Dopplerjet parallel to the insonation beam and resultsin an on-axis, continuous-wave DopplerTR tracing (Figure 2A and 2B) (17). Specklestrain imaging was performed using TomTecImage-Arena software (TOMTEC Corp., USA,Chicago, Illinois) for assessment of globallongitudinal strain, using the 4-chamber view(Figure 2C and 2D). Measures of tricuspidmorphology included tenting height and area(4-chamber view). Quantitation of TR wasperformed using multiple methods accordingto guidelines (18) and previously describedquantitative Doppler methods (19).
Transesophageal echocardiography. Comprehensivetransesophageal echocardiography (TEE) studieswere performed as per American Society of Echocar-diography Guidelines (20). Focused tricuspid valveimaging was performed as previously described (19)using both 2-dimensional (2D) (Figure 3A and 3B) and3D (Figure 3C and 3D) modalities. Using 3D volumes, aplanar cross-sectional area of the tricuspid annulus(TA) was measured in early systole and mid-diastole(Figure 3E), with quantitation of the regurgitationperformed both by quantitative Doppler and 3Dplanimetry of the color Doppler vena contracta area(Figure 3F). Valve size was determined using anintegrative approach.Computed tomography. Patients underwent electro-cardiographically-gated computed tomographic (CT)angiography following a dedicated tricuspid protocolusing a 320-slice system (Toshiba Medical Systems,Otawara, Japan). Intravenous injection of nonioniccontrast agent (iodixanol) was performed using atriphase protocol as follows: 60%/40% contrast/salinemixture at a rate of 4 ml/s, followed by 25%/75%contrast saline mixture at a rate of 4 ml/s, and finally,20 ml of normal saline at 4 ml/s (total contrast vol-ume: 61 ml). The TA was defined as the plane of thevirtual circumferential ring that contained the basalattachment points of the 3 tricuspid valve leaflets(Figure 4A and 4B). In addition to a nonplanar mea-surement of the TA area, a planar cross-sectional areawas measured in early systole and mid-diastole(Figure 4C and 4D). Finally, the transatrial accessapproach with the most co-axial deployment axisperpendicular to the centroid point of the cubic splinethat interpolated the TA (Figure 4D) was determinedwith 3D reconstruction of this location (Figure 4E),and volume rendering of the surgical view (Figure 4F)
valve

FIGURE 1 The GATE System

A

B

C

Stent Inflow View Outflow View Side View

The GATE System is composed of an atrioventricular valved stent (A), the delivery system (B), a compression loading system, introducer sheath (C), and dilator.

Hahn et al. J A C C : C A R D I O V A S C U L A R I M A G I N G , V O L . 1 2 , N O . 3 , 2 0 1 9

Transcatheter Tricuspid Valve M A R C H 2 0 1 9 : 4 1 6 – 2 9

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was determined using dedicated software (3mensiovalves, version 9.0, Pie Medical Imaging, Maastricht,the Netherlands). Using either CT or TEE TA mea-surements for sizing, the implanted GATE valve wasoversized by 2% to 5% according to the area-derivedaverage diameter.

PROCEDURAL STEPS. Following double lumenendotracheal tube intubation, right coronary arteryangiography and placement of a coronary guidewirewas performed to help define the TA plane fluoro-scopically. In all cases, the tricuspid valve wasapproached through a surgical, direct transatrialapproach. A minimally invasive right thoracotomywas performed in the intercostal space identified bypre-operative CT to provide the best perpendicular

TABLE 1 Sizing Chart for the GATE System

ModelAVS-EXD Size (mm)

Intended TAD of NativeTricuspid Valve (mm)

OutflowDiameter (mm)

1002-40 40 36–39 40

1002-44 44 40–43 44

1002-48 48 44–47 48

1002-52 52 48–52 52

AVS-EXD ¼ atrioventricular valved stent-external diameter; TAD ¼ tricuspid annular dia

access to the tricuspid valve (Figure 5A). The rightlung was deflated, and the pericardium was opened 1to 2 cm above the phrenic nerve to the mid-free wallof the right atrium (RA). Balloting the RA wall with aforceps was performed during simultaneous TEE im-aging (Figure 5B) to confirm that the location of theatriotomy and the intended trajectory of the deliverysystem had ideal perpendicular alignment with theannular plane. After full heparinization with a goalactivated clotting time of >250, 2 4-0 PROLENEPolypropylene Suture (Ethicon US, LLC, Somerville,New Jersey) purse string sutures with pledgets wereplaced at the site of the intended atriotomy. Apuncture was made with introduction of a wire andpigtail across the annulus. A stiff wire was then

InflowDiameter (mm)

Inflow WingletsDiameter (mm)

Outflow TinesDiameter (mm)

Height(mm)

30 43 45 18.2

33 48 49 19.4

36 49 55 22.0

40 57 58 21.4

meter.

FIGURE 2 Representative Examples of Advanced Assessment of RV Function

A B

C D

(A and B) Measurement of right ventricular (RV) change in pressure divided by change in time (dP/dT) on representative beats for Patients #2

and #4, who had the highest and lowest values, respectively. The global longitudinal strain (GLS) measurement for these same 2 patients are

shown in (C and D), respectively.


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introduced over the pigtail catheter and positioned inthe RV apex (Figure 5C). The puncture site wasdilated, and the introducer sheath was positionedwith the tip 2 to 3 cm into the RA. The delivery systemwas then introduced into the RA, and purse stringswere secured around the system.

Using TEE guidance, the delivery system wascentered in the annulus, with the shaft perpendicularto the annular plane (Figure 5D). The delivery systemwas advanced across the TA and re-centered beforethe valve capsule was slowly withdrawn by rotating aknob on the delivery system handle, exposing the

ventricular tines of the atrioventricular valved stent(Figure 6A and 6B). The partially unsheathed valvewas then re-positioned with the distal end just belowthe leaflet tips, which allowed imaging of leafletengagement between the body of the valve and thetines (Figure 6C and 6D). At this point, the atrial brimwas still restrained, and some repositioning waspossible to ensure that the proximal edge of the de-vice was within the atrium before deploying the atrialend. Once the atrial brim was deployed (Figure 6E and6F), the delivery system was carefully withdrawn,and the atriotomy and right thoracotomy closed.

FIGURE 3 Pre-Procedural TEE

D1 - 445 cm

Distance(s)

D2 - 428 cm

A1 - 1538 cm

A1 - 0.71 cm

Area(s)

Area(s)

2

2

A2 - 0.81 cm2

A3 - 0.63 cm2

A4 - 0.70 cm2

A5 - 0.85 cm2

A6 - 1.02 cm2

A7 - 1.34 cm2

A8 - 1.37 cm2

A10 - 0.95 cm2

A19 - 1.09 cm2

A11 - 0.53 cm2

A B

CRH2 TEEX7-2t11Hz7.6cm3D 2.0m 2D/3D%42/33C 50/30Pen

D

E F

Focused tricuspid valve imaging was performed using (A and B) 2-dimensional (2D) and (C and D) 3-dimensional (3D) modalities. (E) A planar

cross-sectional area was measured in early systole and mid-diastole using multi-planar reconstruction with (F) quantitation of the regur-

gitation performed both by quantitative Doppler and 3D planimetry of the color Doppler vena contracta area. TEE ¼ transesophageal

echocardiography.



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FIGURE 4 Pre-Procedural CT

Systolic phase: Diastolic phase

A B

C D

E F

Marker1Marker1

Three-dimensional computed tomography (CT) reconstruction of the nonplanar TA is shown in (A) long- and (B) short-axis planes. (C and D)

A planar cross-sectional area was also measured in early systole and mid-diastole. Finally, the transatrial access approach, in which the most

co-axial deployment angle to (E) the TA was determined with (F) 3D reconstruction of this location.


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Final imaging of the valve position, shape, andfunction was performed using both fluoroscopy andTEE (Figures 6G and 6H). Post-operative care includedroutine drain care and long-term anticoagulation withwarfarin for clinical indications.

RESULTS

BASELINE PATIENT CHARACTERISTICS. The base-line clinical characteristics of the 5 patients are listedin Table 2. All patients were symptomatic despite

FIGURE 5 Procedural Imaging

A B

C D

1 cm

Nosecone

RA

RV

AnnularPlane

HR 59

(A) A minimally invasive right thoracotomy was performed in the fourth intercostal space, mid-posterior axillar line. (B) Balloting the right

atrial (RA) wall with a forceps (yellow arrow) was performed to confirm that the location of the atriotomy and intended trajectory of

atrioventricular valved stent delivery. (C) A stiff wire was then introduced over the pigtail catheter and positioned in the RV (yellow arrow).

The site was dilated and the introducer sheath positioned with the tip 2 to 3 cm into the RA (red arrow). (D) Using 3D transesophageal

imaging, the delivery system is centered in the annulus (yellow-white crossing arrows). Abbreviations as in Figures 2 and 3.



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aggressive diuretic therapy as per guidelines (21). Allpatients were in atrial fibrillation or had a history ofparoxysmal atrial fibrillation. All patients had multi-ple comorbidities, including a history of cardiac sur-gery in 4 of the 5 patients. Three of the 5 patients hadchronic ascites that required serial paracenteses.

Baseline echocardiographic parameters are listedin Table 3. All patients had a dilated RV and TAdiameter. Two of the patients (#2 and #5) had nosignificant tenting despite the dilated RA and RV,

which is consistent with idiopathic functional TR. Allpatients had massive or torrential TR (22). At least 1measure of RV function was abnormal in all patients.One patient had severe left ventricular dysfunction(#4) and had a pacemaker traversing the tricuspidvalve annulus. Estimated pulmonary artery pressureswere variable by echocardiography.

CLINICAL AND ECHOCARDIOGRAPHIC OUTCOMES.

All patients were admitted 3 to 5 days before the

FIGURE 6 Valve Deployment

A

C

E

G

B

D

F

H

(A and B) Once centered in the annulus the valve capsule is withdrawn exposing the ventricular tines of the atrioventricular valved stent.

(C and D) The valve is then positioned just below the leaflet tips, with imaging of leaflet engagement between the body of the valve and the

tines before completion of ventricular release. (E and F) The atrial brim is deployed, and the delivery system is carefully withdrawn. (G) Trivial

tricuspid regurgitation is seen on both right ventriculography and (H) echocardiography (white arrow).


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TABLE 2 Baseline Clinical Characteristics

Patient #1 Patient #2 Patient #3 Patient #4 Patient #5

Age (yrs) 93 91 78 80 80

Sex Male Female Male Male Female

NYHA functional class III II III III III

Rhythm P. AF AF AF AF AF

Concomitant disease HTN, DM, CAD, TIAs HTN, DM,hypothyroid,

CABG

HTN, DM, CABG,laryngeal cancer,B-cell lymphoma

HTN, CABG, MVrepair, CVA, AICD

AVR, MVR

Kidney disease Stage 3 Stage 1 Stage 1 Stage 3 Stage 3

Liver disease Mild Normal Normal Cirrhosis Mild

Other relevant clinical history Frequent paracenteses Thoracenteses,paracenteses

Paracenteses

Cardiac medications Furosemide 80 mg,Metolazone 5 mg,Aldactone 25 mg

Furosemide80 mg

Furosemide 40 mg,Metolazone 2.5 mg

Bumex 1 mg,Metolazone 2.5 mg

Carvedilol 12.5 mg,Furosemide 40

mg

Hemoglobin (g/dl) 8.7 11.6 12.3 10.1 6.3

Bilirubin (mg/dl) 0.3 0.7 1.1 1.2 0.3

Sodium (mmol/l) 136 141 137 137 141

Creatinine (ml/dl) 1.89 0.99 1.47 2.26 0.9

eGFR (ml/min/1.73 m2) 41 >60 >60 34 48

Albumin (g/dl) 2.8 3.6 4.7 3.4 3.0

Total protein (g/dl) 5.1 6.0 7.7 7.6 4.7

AST (U/l) 40 41 40 17 28

ALT (U/l) 16 18 25 9 10

AlkPhos (U/l) 556 61 132 134 48

NT-ProBNP (pg/ml) 9,524 1,037 1,465 1,688 1,707

In-hospital outcomes

Significant bleeding No No Yes (chest wall) Yes (chest wall) Yes (esophageal,chest wall)

Stroke No No No No No

Myocardial infarction No No No No No

Other complications None None Temporary pacer forbradycardia

CVVH None

ICU stay (days) 5 2 28 28 3

Length of stay (days) 13 5 43 Expired 28 8

AF ¼ atrial fibrillation; AICD ¼ automatic implantable defibrillator; AlkPhos ¼ alkaline phosphatase; AST ¼ aspartate aminotransferase; ALT ¼ alanine aminotransferase; AVR ¼aortic replacement; CABG ¼ coronary artery bypass grafting; CAD ¼ coronary artery disease; CVA ¼ cerebral vascular accident; CVVH ¼ continuous veno-venous hemofiltration;DM ¼ diabetes mellitus; eGFR ¼ estimated glomerular filtration rate; HTN ¼ hypertension; ICU ¼ intensive care unit; MV ¼ mitral valve, MVR ¼ mitral valve replacement;NT-ProBNP ¼ N-terminal pro�B-type natriuretic peptide; NYHA ¼ New York Heart Association; P.AF ¼ paroxysmal atrial fibrillation; TIAs ¼ transient ischemic attacks.



424

procedure and treated with intravenous diuretics astolerated to achieve a reduction in weight with aclinical improvement in peripheral edema.

Technical success was 100%, with implantation ofa single valve in the appropriate position and suc-cessful retrieval of the delivery system in all cases.The threshold for the pacemaker in Patient #4 wasunchanged after implantation of the transcathetervalve. Inotropic support was required immediatelyfollowing the procedure for 3 patients (#3, #4, and#5). Intraprocedural TEE results are listed in Table 3.The GATE valve was slightly canted in patient #1,with the posterior edge of the device seated moreatrially (Figure 7A), which resulted in mild posteriorparavalvular and mild central regurgitant jets. Allsubsequent valves were well positioned in theannulus, with trace to mild TR seen following valve

deployment. Peak and mean transtricuspid gradientswere low (mean gradient <1.0 mm Hg). One patient(#3) required re-exploration for chest wall bleeding.One patient (#4) died on post-operative day 28; thispatient experienced prolonged mechanical ventila-tion, re-intubation, and renal failure that requiredcontinuous veno-venous hemofiltration. All otherpatients were discharged to home (#2 and #5) or to arehabilitation facility (#1 and #3). There were nostrokes or myocardial infarctions. A temporary pace-maker was placed in patient #3 for symptomaticbradycardia, but a permanent pacemaker was notrequired.

All discharged patients were on anticoagulants,except for Patient #5, who was discharged on aspirinalone in the setting of extensive bleeding (esophagealand pleural) during her hospitalization. She was

TABLE 3 Baseline and Follow-Up Echocardiographic Parameters

Baseline Echo Parameters Case #1 Case #2 Case #3 Case #4 Case #5

LVIDD (cm) 4.4 3.6 3.9 5.8 3.3

LVIDS (cm) 3.2 2.3 2.8 4.9 2.8

LVEF (%) 75 65 55 25 57

RV basal diameter (cm) 6.0 4.6 5.9 5.2 5.5

RV mid diameter (cm) 3.8 3.9 4.0 3.7 4.8

TAPSE (cm) 0.8 1.4 1.1 1.0 1.2

Fractional area change (%) 41 43 26 29 38

RV systolic TDI (cm/s) 13 12 7 9 9

Global longitudinal strain (RV, %) �28 �19 �16 �12 �19

RV dP/dT (mm Hg/s) 543 583 300 240 501

LVOT stroke volume (cc) 77 49 37 65 75

Aortic regurgitation None None Trace Mild None

Mitral regurgitation Mild Mild Mild Mild None

RA volume index (ml/m2) 94.6 70.4 149 88 97.2

TV annular diameter (4Ch, end-diastole) (cm) 4.0 4.8 4.7 4.2 4.6

Tenting height (mm) 8.8 4.4 5.9 0.73 0

Tenting area (cm2) 1.69 0.96 1.04 1.04 0

EROA PISA (cm2) 0.73 0.63 0.78 0.7 0.75

PISA regurgitant volume (ml) 74 70 57 69 43

2D quantitative EROA (cm2) 0.76 0.96 1.75 1.5 2.2

Doppler regurgitant volume (ml) 74 107 127 147 125

Hepatic vein systolic reversal Yes Yes Yes Yes Yes

TR velocity (m/s) 3.17 3.50 2.67 3.17 1.81

Estimated PASP (mm Hg) 55 65 34 55 28

TR contour Parabolic Parabolic Triangular Parabolic Parabolic

Baseline 3D TEE annular measurements (early diastolic)

Minimum/maximum diameters (cm) 4.7 � 4.7 4.3 � 4.8 4.2 � 5.1 4.2 � 4.3 3.2 � 4.7

Annular area�derived diameter (cm) 4.5 4.5 4.8 4.2 4.3

Baseline CT annular measurements (end-diastolic)

Minimum/maximum diameters (cm) 4.3 � 4.9 4.7 � 5.0 42.1 � 5.7 4.2 � 4.4 3.9 � 5.1

Annular area�derived diameter (cm) 4.4 4.8 5.0 4.3 4.5

Implanted GATE valve size 48 48 52 44 44

Intraprocedural, post-device TEE

Peak transtricuspid gradient 1.4 1.5 0.8 2.5 1.0

Mean transtricuspid gradient 0.8 0.5 0.3 0.8 0.5

Tricuspid valve area (by CE, in cm2) 3.5 3.1 3.1 2.7 2.2

Tricuspid regurgitation (total) Mild�moderate Trace Mild Mild Trace

Central Mild Trace Mild None None

Paravalvular Mild (posterior) Trace (septal) None Mild (lateral andat wire)

Trace(anterior)

2D ¼ 2-dimensional; 4Ch ¼ 4 chamber; dP/dT ¼ change in pressure divided by the change in time; CE ¼ continuity equation; CT ¼ computed tomography; EROA ¼ effectiveregurgitation orifice area; LVEF¼ left ventricular ejection fraction; LVIDD¼ left ventricular internal dimension in diastole; LVIDS ¼ left ventricular internal dimension in systole;LVOT ¼ left ventricular outflow tract; PASP ¼ pulmonary artery systolic pressure; PISA ¼ proximal isovelocity surface area; RA ¼ right atrium; RV ¼ right ventricular; TAPSE ¼tricuspid annular plane systolic excursion; TDI ¼ tissue Doppler imaging; TEE ¼ transesophageal echocardiography; TR ¼ tricuspid regurgitation.


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readmitted on post-operative day 28 with a fluidcollection over the right chest wall, which wasdetermined to be a seroma. A TTE at that timerevealed restricted leaflet motion with thrombus onboth atrial and ventricular sides of the cusps(Figure 7B and 7C), with a peak and mean gradient of4.7 and 3.4 mm Hg, respectively, and an estimatedvalve area of 0.9 to 1.4 cm2 (significantly reduced).The patient was treated with warfarin and follow-upafter 8 weeks showed complete resolution of

thrombus (Figure 7D), with peak and mean gradientsof 1.5 and 0.8 mm Hg, respectively.

On 30-day follow-up, all patients reportedimprovement in symptoms, as well as evidence for RVremodeling and an increase in forward cardiac outputon echocardiography (Table 4). No patient had achange in the severity of paravalvular regurgitation atfollow-up. One patient (#3) had a small fistula be-tween the noncoronary aortic sinus of Valsalva andthe RV (just beneath the septal tricuspid valve leaflet)

FIGURE 7 Complications Following Valve Deployment

A E

B C D

LA LA

AV

RV RV

AortaRARA

R R

AV

RVRV

RV RVRV

RA RA RA RA

30d TTE 30d TTE 3mo TTE

CS

LALA

TEE following deployment in (A) patient #1 showed a malpositioned device (yellow box). The blue dotted line indicates the annular plane with the posterior edge

atrially displaced in the orthogonal biplane view. (B to D) The transthoracic echocardiographic (TTE) imaging of Patient #5 with is marked tissue-density thickening of

the leaflets (B) (yellow arrows) and a narrow, high-velocity transtricuspid diastolic jet (C) (red arrows). (D) Following 8 weeks of Coumadin, the leaflet motion and

thickness were normal (yellow arrows) with laminar transtricuspid diastolic flow (red arrows). Patient #3 had a small fistula detected between the aorta and the RV

initially on transthoracic echocardiography. (E) TEE confirmed the fistula with color Doppler revealing a narrow jet from the right coronary sinus of Valsalva to the RV

outflow tract (red arrow). AV ¼ aortic valve; CS ¼ coronary sinus; LA ¼ left atrium; other abbreviations as in Figures 2 and 5.



426

on in-hospital echocardiograms (Figure 7E) but didnot require intervention.

DISCUSSION

The available transcatheter tricuspid repair devicesaddress specific anatomic abnormalities associatedwith primary or secondary TR. Annular devicesattempt to reduce annular area and improve coapta-tion, but similar to their surgical counterparts, theyare unlikely to result in a durable reduction in TR ifconcomitant RV dysfunction or dilatation exists.Leaflet devices such as spacers or clips reduce thearea of the functioning valve, and a reduction in RApressures may not occur. Furthermore, most repairdevices have reported incomplete reduction of TR(11,23,24). As in the case of functional mitral valve

regurgitation (25), it is possible that the durable so-lution for TR will require a valve replacement.

In this small series of patients who underwentcompassionate use of TTVR for severe, symptomaticTR, there are a number of important observationsspecific to the current device. First, pre-implantsizing can be performed using multiple differentmodalities; however, the minimal oversizing usingintra-procedural TEE measurements may be ideal forthis device. Second, procedural success is dependenton TEE guidance with frequent use of advanced,real-time 3D tools, which enables precise placementof the valve in the annulus despite the nonplanaranatomy. Although fusion imaging and intracardiacechocardiography was not used, these imaging toolscould also be helpful. Third, TTVR practically elimi-nates TR in a patient population with massive or

TABLE 4 Baseline and 30-Day Echocardiographic Measurements

Case #1 Case #2 Case #3 Case #4 Case #5

Pre 30 Days Pre 30 Days Pre 30 Days Pre 30 Days Pre 30 Days

RV basal diameter (cm) 6.0 4.9 4.6 4.0 5.9 3.9 5.2 NA 5.5 4.7

RV mid diameter (cm) 3.8 3.7 3.9 3.2 4.0 3.0 3.7 NA 4.8 3.3

TAPSE (cm) 0.8 0.8 1.4 0.8 1.1 1.0 1.0 NA 1.2 0.3

Fractional area change (%) 41 37 43 38 26 23 29 NA 38 32

LVOT stroke volume (cc) 77 46 49 54 40 58 53 NA 69 54

Cardiac output (l/min) 3.4 4.5 4.3 4.9 3.6 4.4 3.5 NA 4.8 4.9

Pre ¼ baseline transthoracic echocardiographic measurements; other abbreviations as in Table 3.


427

torrential disease. However, the elimination of TRmay not be tolerated in patients with significantlyreduced RV function. In this series, the patients withthe worst RV function had the worst clinical out-comes (inotropic dependence, increased length ofstay, and in-hospital mortality). Fourth, the largedelivery sheath requires a transatrial approach thatcan result in surgical or chest wall bleeding in thiscoagulopathic population, requires mechanicalventilation that increases pulmonary complications,and also lengthens hospital stay; a percutaneoustransvenous approach is highly desirable and forth-coming. When the procedure becomes completelypercutaneous, TTE imaging may also be used. Fifth,liver cirrhosis and advanced renal impairment werelikely contributors to the only in-hospital mortality,and patients with advanced sequelae of TR and rightheart failure may not benefit from this procedure.Sixth, anticoagulation will likely be necessary toprevent valve thrombosis because of the large size ofboth these valves, as well as the lower RV pressures.Finally, despite multiple comorbidities, those pa-tients who survived to 30 days had RV remodelingand an increase in cardiac output.

Device implantation and retrieval of the deliverysystem was achieved in all patients, and the valveperformed as expected. The peak and mean gradi-ents across the transcatheter valve were very lowin the setting of large valve areas. Equally impres-sive was the nearly complete elimination of verysevere TR. Using the proposed extended gradingscheme (22), the patients in this series had morethan severe TR according to different methods,with the 4 of 5 patients having massive (95 to 114mm2) or torrential ($115 mm2) TR according toquantitative Doppler. Post-implantation TR wasmild to moderate only in the first patient, who hadslight malpositioning likely due to a procedurallearning curve. All other patients had well-positioned valves with trace to mild paravalvularor central regurgitation. In addition, the valve was

successfully placed in a patient with a pre-existingpacemaker with minimal paravalvular regurgitationaround the pacing lead and no change in the pacingthreshold.

Complete elimination of TR may not be tolerated inall patients. Because regurgitation into a lower resis-tance chamber (e.g., the RA) effectively reduces RVafterload, elimination of TR may increase RV after-load, and, in failing ventricles, cardiac output mayactually fall. This is the first study to show that bothstrain imaging and RV dP/dT may be useful markersof baseline RV contractility. RV dP/dT represents theinstantaneous rate of RV pressure rise during earlysystole and is a surrogate marker of RV contractility.Studies in patients with pulmonary hypertensioncorrelated RV dP/dT with pulmonary artery systolicpressure (r ¼ 0.73; p < 0.001), TAPSE (r ¼ 0.45; p <

0.001), and left ventricular fractional shortening (r ¼0.40; p < 0.01) (17). RV dP/dT has been significantlycorrelated to RV ejection fraction by cardiac magneticresonance imaging (r2 ¼ 0.51; p < 0.01), and a RV dP/dT >400 mm Hg/s had a positive predictive value of91%, and sensitivity and specificity of 74% and 84%,respectively, for a normal RV ejection fraction (26). Inpatients with pulmonary arterial hypertension andchronic thromboembolic pulmonary hypertension, areduced baseline RV dP/dT is an indicator of pooroutcome independent of TAPSE (27). In our smallseries, the patient with the worst RV dP/dT did notsurvive the initial hospitalization, and the patientwith RV dP/dT <400 mm Hg/s had a prolonged hos-pital course. Because this parameter can be derivedfrom the TR velocity profile, and thus multiple cyclescan be averaged for those patients in atrial fibrilla-tion, it may be a simpler measure of RV functioncompared with strain imaging, which requiresadvanced imaging packages. Because of the smallnumber of patients, these results are hypothesis-generating only, and larger outcomes studies shouldbe performed to assess the performance of theseparameters.

PERSPECTIVES

COMPETENCY IN MEDICAL KNOWLEDGE: Im-

plantation of a first-generation TTVR device is tech-

nically feasible in patients with more than severe TR.

TTVR is associated with RV remodeling, increased

cardiac output, and improvement in New York Heart

Association functional class in most patients; howev-

er, predictors of poor clinical outcomes may be the

extent of existing co-morbidities and RV dysfunction.

TRANSLATIONAL OUTLOOK: Elimination of TR

using a transcatheter replacement device may not be

appropriate in all patients. Determining the appro-

priate patient population that will benefit from this

therapy requires additional studies.



428

Both TEE and CT measurements of the annuluswere used in this series. Although cardiac magneticresonance imaging was not used, this modality canalso measure the annulus (28). CT and TEE mea-surements were discordant in only patient #3, inwhom intra-procedural TEE measurements supportedthe use of a 48-mm valve, but the CT measurementssuggested a 52-mm valve. This patient subsequentlywas found to have a small aortic perforation from aventricular tine likely related to oversizing of thevalve. In this instance, the 52-mm valve chosen rep-resented a 4% oversizing by CT, but an 8% oversizingby TEE. Unlike transcatheter aortic valve replace-ment, in which oversizing is required to provide a sealand prevent embolization, the tricuspid valveannulus on histological examination has little fibroustissue or collagen (29). Although initially oversizingthe device (similar to practices for the aortic andmitral transcatheter devices) was used, a number offactors led to more nominal sizing for the last 2 pa-tients. First, although the valve was somewhatconformable, most annuli were still elliptical, and inthe longer dimension, the atrial brim, as well as thenormal tricuspid valve leaflet tissue, appeared toprevent paravalvular regurgitation in segments of theannulus that were not in direct contact with the de-vice. Second, the lack of support from a rigid annulusincreased the risk of perforation of adjacent struc-tures or atrioventricular node injury by the ventric-ular tines. Thus, nominal sizing rather thanoversizing was adopted for the last 2 patients. Inthese cases, the valve size was determined by theintraprocedural TEE and the largest derived annulardiameter that considered both the perimeter and areameasurements (typically diastolic). Finally, para-valvular regurgitation in the setting of a low-pressuresystem is unlikely to cause heart failure or hemolysis.Importantly, the annular dimensions were dependentalso on volume status, postural position, and evenrespirations. In-hospital, pre-procedural diuresis wasfrequently used in these patients and may explainwhy the intra-procedural TEE measurements were ingeneral smaller than pre-admission CT measure-ments. All measurements should be consideredcarefully with respect to the patient’s clinical andvolume status at the time of implantation. In addi-tion, once the valve is in place (and TR relieved),response to outpatient diuretics allows for bettervolume control.

Anticoagulation following implantation of theselarge tissue valves will likely be necessary. Patients #1to #3 were admitted with and discharged on anti-coagulation in the setting of chronic or paroxysmalatrial fibrillation. Patient #5 was admitted with chronic

atrial fibrillation; however, in the setting of bleedingcomplications before and following valve implanta-tion, she was discharged on aspirin alone. Her follow-up TTE showed extensive thrombus on the valve,which resulted in significant tricuspid valve stenosisdespite the patient reporting a significant clinicalimprovement. Following 8 weeks of anticoagulationwith warfarin, the leaflet thrombus resolved, and peakand mean gradients returned to immediate post-implantation levels. Whether vitamin K antagonists,direct oral anticoagulants, or dual anti-platelet agentsshould be used requires further study.

STUDY LIMITATIONS. This was a small initial seriesof patients, and validation of sizing algorithms andmeasures of outcome for TTVR must be validated in alarger patient population. In addition, althoughmultiple cardiac cycles were averaged to measuremost RV parameters, a single cycle was used for strainimaging, which, for patients in atrial fibrillation,might not be representative of overall RV function.

CONCLUSIONS

In this series of patients with symptomatic, very se-vere functional TR, TTVR was feasible with short-term improvement in RV remodeling and cardiacoutput. Comorbidities, particularly RV function,might be important determinants of outcomes.

ADDRESS FOR CORRESPONDENCE: Dr. Rebecca T.Hahn, Columbia University Medical Center, NewYork-Presbyterian Hospital, 177 Fort WashingtonAvenue, New York, New York 10032. E-mail: [email protected].

mailto:[email protected]

mailto:[email protected]


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RE F E RENCE S

1. Najib MQ, Vinales KL, Vittala SS, Challa S, Lee HR,Chaliki HP. Predictors for the development of severetricuspid regurgitation with anatomically normalvalve in patients with atrial fibrillation. Echocardi-ography (Mount Kisco, NY) 2012;29:140–6.

2. Kwak JJ, Kim YJ, Kim MK, et al. Development oftricuspid regurgitation late after left-sided valvesurgery: a single-center experience with long-term echocardiographic examinations. Am HeartJ 2008;155:732–7.

3. Nath J, Foster E, Heidenreich PA. Impact oftricuspid regurgitation on long-term survival. J AmColl Cardiol 2004;43:405–9.

4. Voelkel NF, Quaife RA, Leinwand LA, et al.Right ventricular function and failure: report of aNational Heart, Lung, and Blood Institute workinggroup on cellular and molecular mechanisms ofright heart failure. Circulation 2006;114:1883–91.

5. Bustamante-Labarta M, Perrone S, De LaFuente RL, et al. Right atrial size and tricuspidregurgitation severity predict mortality or trans-plantation in primary pulmonary hypertension.J Am Soc Echocardiogr 2002;15:1160–4.

6. Alqahtani F, Berzingi CO, Aljohani S, Hijazi M,Al-Hallak A, Alkhouli M. Contemporary trends inthe use and outcomes of surgical treatment oftricuspid regurgitation. J Am Heart Assoc 2017;6.

7. Sales VL, McCarthy PM. Durability of functionaltricuspid valve repair. Semin Thorac CardiovascSurg 2010;22:97–103.

8. Zack CJ, Fender EA, Chandrashekar P, et al.National trends and outcomes in isolated tricuspidvalve surgery. J Am Coll Cardiol 2017;70:2953–60.

9. Rodes-Cabau J, Hahn RT, Latib A, et al. Trans-catheter therapies for treating tricuspid regurgi-tation. J Am Coll Cardiol 2016;67:1829–45.

10. Hahn RT, Meduri CU, Davidson CJ, et al. Earlyfeasibility study of a transcatheter tricuspid valveannuloplasty: SCOUT trial 30-day results. J AmColl Cardiol 2017;69:1795–806.

11. Nickenig G, Kowalski M, Hausleiter J, et al.Transcatheter treatment of severe tricuspidregurgitation with the edge-to-edge mitracliptechnique. Circulation 2017;135:1802–14.

12. Campelo-Parada F, Perlman G, Philippon F,et al. First-in-man experience of a novel trans-catheter repair system for treating severe tricuspidregurgitation. J Am Coll Cardiol 2015;66:2475–83.

13. Rosser BA, Taramasso M, Maisano F. Trans-catheter interventions for tricuspid regurgitation:TriCinch (4Tech). EuroIntervention 2016;12:Y110–2.

14. Figulla HR, Kiss K, Lauten A. Transcatheterinterventions for tricuspid regurgitation - hetero-topic technology: TricValve. EuroIntervention2016;12:Y116–8.

15. Taramasso M, Pozzoli A, Guidotti A, et al.Percutaneous tricuspid valve therapies: the newfrontier. Eur Heart J 2017;38:639–47.

16. Lang RM, Badano LP, Mor-Avi V, et al. Rec-ommendations for cardiac chamber quantificationby echocardiography in adults: an update from theAmerican Society of Echocardiography and theEuropean Association of Cardiovascular Imaging.J Am Soc Echocardiogr 2015;28:1–39 e14.

17. Pai RG, Bansal RC, Shah PM. Determinants ofthe rate of right ventricular pressure rise byDoppler echocardiography: potential value in theassessment of right ventricular function. J HeartValve Dis 1994;3:179–84.

18. Zoghbi WA, Adams D, Bonow RO, et al. Rec-ommendations for noninvasive evaluation ofnative valvular regurgitation: a report from theAmerican Society of Echocardiography developedin collaboration with the Society for Cardiovascu-lar Magnetic Resonance. J Am Soc Echocardiogr2017;30:303–71.

19. Hahn RT. State-of-the-art review of echocar-diographic imaging in the evaluation and treat-ment of functional tricuspid regurgitation. CircCardiovasc Imaging 2016;9.

20. Hahn RT, Abraham T, Adams MS, et al.Guidelines for performing a comprehensivetransesophageal echocardiographic examination:recommendations from the American Society ofEchocardiography and the Society of Cardiovas-cular Anesthesiologists. J Am Soc Echocardiogr2013;26:921–64.

21. Nishimura RA, Otto CM, Bonow RO, et al. 2017AHA/ACC Focused Update of the 2014 AHA/ACC

guideline for the management of patients withvalvular heart disease: a report of the AmericanCollege of Cardiology/American Heart AssociationTask Force on Clinical Practice Guidelines. J AmColl Cardiol 2017;70:252–89.

22. Hahn RT, Zamorano JL. The need for a newtricuspid regurgitation grading scheme. Eur HeartJ Cardiovasc Imaging 2017;18:1342–3.

23. Taramasso M, Hahn RT, Alessandrini H, et al.The International Multicenter TriValve Registry:which patients are undergoing transcathetertricuspid repair? J Am Coll Cardiol Intv 2017;10:1982–90.

24. Perlman G, Praz F, Puri R, et al. Transcathetertricuspid valve repair with a new transcathetercoaptation system for the treatment of severetricuspid regurgitation: 1-year clinical and echo-cardiographic results. J Am Coll Cardiol Intv 2017;10:1994–2003.

25. Michler RE, Smith PK, Parides MK, et al. Two-year outcomes of surgical treatment of moderateischemic mitral regurgitation. N Engl J Med 2016;374:1932–41.

26. Singbal Y, Vollbon W, Huynh LT, Wang WY,Ng AC, Wahi S. Exploring noninvasive tricuspid dP/dt as a marker of right ventricular function.Echocardiography 2015;32:1347–51.

27. Ameloot K, Palmers PJ, Vande Bruaene A,et al. Clinical value of echocardiographic Doppler-derived right ventricular dp/dt in patients withpulmonary arterial hypertension. Eur H J Car-diovasc Imaging 2014;15:1411–9.

28. Medvedofsky D, Jimenez JL, Addetia K, et al.Multi-parametric quantification of tricuspidregurgitation using cardiovascular magnetic reso-nance: a comparison to echocardiography. Eur JRadiol 2017;86:213–20.

29. Messer S, Moseley E, Marinescu M, Freeman C,Goddard M, Nair S. Histologic analysis of the rightatrioventricular junction in the adult human heart.J Heart Valve Dis 2012;21:368–73.

KEY WORDS tricuspid regurgitation,tricuspid valve, valve replacement

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