Study of the Clinical Impact of Surgical Correction of Tricuspid Insufficiency in Implantable LVAD Patients

Participant recruitment: At University of Washington Medical Center, 30 to 40 patients with
mild tricuspid valve regurgitation (TR) receive LVAD placement annually. A predicted 50 - 60%
of these patients will agree to be enrolled in this study, for an estimation of 15 to 20
participants a year. With an enrollment period of 2 years, the study aims to enroll 30 to 40
participants

Study interventions and Specific Techniques: Prior to screening data collection and protocol
defined procedures, the participant must sign the consent form. Within 30 days prior to
randomization (as part of routine clinical care), a complete transthoracic echocardiogram
will be performed, evaluated, and reported. Within 7 days prior to randomization (as part of
routine clinical care): 1) a medical history and physical exam is performed; 2) New York
Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) Classes are established
and documented; 3) all current medications and therapies are recorded on study documents; 4)
the participant will complete the Duke Activity Status Index for quality of care (QOL)
assessment.

Randomization: Randomization procedure will be performed intra-operatively, following
sternotomy and before cannulation of aorta. Randomization will follow a computer generated
simple randomization process. Participants will be randomized with equal probability to
receive LVAD implantation alone or LVAD implantation plus surgical repair of their tricuspid
valve (TV). The nature of the treatments precludes masking of participants and their treating
clinicians to treatment assignment.

Surgical technique: Participants randomly assigned to receive tricuspid valve repair (TVR) in
addition to LVAD implantation will undergo repair with standard techniques. After bicaval
cannulation and with the heart beating, a right atriotomy is created and the TV exposed. A
patent foramen ovale (PFO), if present, is closed primarily. 2-0 braided sutures are placed
radially through the tricuspid annulus from the lateral fibrous trigone counterclockwise to
the medial fibrous trigone, thus avoiding the conduction system. An incomplete semi-rigid
annuloplasty ring is then suspended after appropriate sizing. Any ventricular pacing leads
are then mobilized from leaflet and subvalvular adhesions and placed in the commissure
between the septal and posterior leaflets. The septal and posterior leaflets are then
approximated from the junction of the rough and smooth zone back to the leads, bicuspidizing
the valve, and trapping the ventricular leads away from the tricuspid valve orifice.

Tricuspid valve assessment: The 3 leaflets of the TV will be assessed with echocardiography.
The midesophageal inflow-outflow view and the midesophageal modified bicaval TV view will be
chosen for Doppler interrogation of transvalvular flow. 3D examinations will also be
assessed. 3D Transesophageal echocardiography (TEE) permits the precise description of the
elliptical shape of the TV annulus and its dimensions in a clinically feasible fashion.

Assessment of TR severity will include several echocardiographic parameters such as right
ventricle (RV), right atrium, and inferior vena cava size, area of the regurgitant jet, width
of the vena contracta (VC), proximal isovelocity surface area, TR jet density and contour, as
well as hepatic vein flow patterns. The VC is a surrogate measurement for the effective
regurgitant orifice area (EROA). Using sequential cropping techniques that keep the cropping
plane precisely parallel to the TV orifice, the vena contracta area (VCA) of the TR jet can
be obtained under 3D TEE assessment.

Right ventricular function: RV diastolic function will be assessed using pulsed-wave Doppler
interrogation of the tricuspid valve, the pulmonary and hepatic venous flow rates, as well as
examination of the tricuspid annulus using tissue Doppler where necessary. With this, the
investigators will measure the tricuspid annular plane systolic excursion (TAPSE), and the
Tei index. The Tei index or right ventricular index of myocardial performance (RIMP) is
defined as the sum of isovolumetric contraction and relaxation intervals divided by ejection
time and is an indicator of systolic and diastolic RV dysfunction.

With transthoracic echocardiography (TTE), a RIMP > 0.40 by pulsed Doppler and > 0.55 by
tissue Doppler suggests RV dysfunction. The investigators will also measure tricuspid annular
velocity using intraoperative TEE. The tissue Doppler derived tricuspid lateral annular
systolic velocity (S') is an alternative parameter to assess RV function, which has been
shown to correlate well with other measures of global RV systolic function. S' velocity < 10
cm/s indicates RV systolic dysfunction.The last measurement for RV function will be the rise
of the RV to right atrial pressure gradient during systole (dP/dT). The correlation of RV
dP/dT with TAPSE and RV ejection fraction will represent another estimate of global RV
function that can easily be determined using Doppler echocardiography.

Perioperative management: A variety of strategies may be utilized to optimize postoperative
ventricular function. These strategies may include pacing, infusions of vasopressors or
positive inotropic agents including both beta receptor agonists and/or phosphodiesterase
inhibitors such as milrinone. Occasional participants may require additional mechanical
support, either intra-aortic balloon pumping or right ventricular assist device, and
Extracorporeal Life Support (ECLS).

Inclusion Criteria:

1. Participant or their legal representative has signed an informed consent

2. Over 18 years of age

3. Participant with advanced heart failure symptoms (Class III or IV) and preoperative
mild tricuspid regurgitation who are scheduled for an implantable LVAD

Exclusion Criteria:

1. Prior tricuspid valve repair

2. Any evidence of structural (chordal or leaflet) tricuspid valve disease

3. Technical obstacles, which pose an inordinately high surgical risk, in the judgment of
the investigator

4. Existence of any ongoing mechanical circulatory support other than intra-aortic
balloon counter pulsation

5. Body Mass Index (BMI) > 45

6. Pregnancy

7. Presence of mechanical aortic valve that will not be converted to a bioprosthesis at
time of LVAD implant

8. History of cardiac transplant or cardiomyoplasty

9. Psychiatric disease, irreversible cognitive dysfunction or psychosocial issues that
are likely to impair compliance with the study protocol and LVAD management

10. Presence of active, uncontrolled infection

11. Evidence of intrinsic hepatic disease as defined by liver enzyme values

12. History of a stroke within 90 days prior to enrollment, or a history of cerebral
vascular disease with significant (> 80%) extra cranial stenosis

13. Need for chronic renal replacement therapy (e.g. chronic dialysis)

14. Participation in any other clinical investigation that is likely to confound study
results or affect study outcome

15. Any condition, other than heart failure, that could limit survival to less than 1 year

16. Participant refuses to be enrolled in study

17. Institution inmates.