ARB-PMCF STUDY: ANNULOPLASTY RINGS & BAND POST-MARKET CLINICAL FOLLOW-UP STUDY

Valve disease is commonly classified as primary or secondary. Congenital or
acquired primary disease directly alters or damages valvular tissue. The most
prevalent primary mitral and tricuspid disease etiologies are degenerative and
rheumatic,both of which are associated with annular dilation and remodeling. In
secondary mitral and tricuspid disease, the deformation and dysfunction of
otherwise normal valvular tissue is caused by diseases of the surrounding
cardiac anatomy, most commonly ischemic cardiomyopathy, left-sided valve
disease, and arrhythmogenic atrial dilation. Enlargement of one or more heart
chambers associated with these diseases can lead to mitral or tricuspid annular
dilation and leaflet tethering that compromise leaflet coaptation. Primary
disease is the most frequent indication for surgical mitral valve repair in the
US, accounting for nearly three quarters of mitral repair surgeries. In recent,
large (N >=180) tricuspid repair studies reporting on consecutive case
series,however, secondary disease is the dominant surgical indication,
accounting for roughly 90% of cases.

The most frequent consequence of mitral and tricuspid disease is valvular
incompetence, where a failure of leaflet coaptation, or a torn or perforated
leaflet, allows regurgitation through the closed valve into the atrium during
systole. Moderate to severe mitral or tricuspid regurgitation are associated
with markedly lower life expectancy. Prevalence estimates based on
echocardiographic exam sampling in the US suggest moderate to severe mitral
regurgitation (MR) is present in 2.0% of all adults and in 7.6% of adults aged
65 or older, while moderate to severe tricuspid regurgitation (TR) is present
in 0.6% of all adults and 2.2% of those over age 65.

Mitral and tricuspid repair surgeries are accepted approaches to treatment of
severe primary mitral or severe primary tricuspid disease. The difference in
prognoses for these conditions with surgical repair as opposed to medical
management alone is stark enough that the superior efficacy of surgical repair
is considered self-evident, even in the absence of randomized controlled
trials. When feasible, repair of primary mitral and tricuspid disease is
preferred to valve replacement in US and European practice guidelines because
the available evidence suggests repair offers both lower perioperative
mortality and higher long-term survival.
Outcomes of secondary MR repair surgery are less favorable than primary MR
repair outcomes. In the largest (N>200) surgical MR repair studies published in
the past 15 years, reported five year survival after primary MR repair ranges
from 82% to 99% with a sample-size-weighted mean of 93%, while after secondary
MR repair the range is 52% to 85% with a sample-size-weighted mean of 71%. Two
recent multicenter, randomized Cardiothoracic Surgery Network (CTSN) studies
have provided further evidence of the limitations of secondary MR repair
surgeries, with results suggesting that surgical replacement is preferable to
surgical repair for severe secondary MR, and that the benefits of moderate MR
repair in conjunction with CABG are doubtful.

There is no broad consensus or medical society guideline on annuloplasty device
selection. Perioperative and long term survival, recurrence of regurgitation,
and reoperation rates have been compared across annuloplasty device types
(e.g., rigid vs. semi-rigid vs. flexible, partial vs. full) in a sizeable
number of retrospective studies, a handful of small randomized trials and
multiple systematic reviews and meta-analyses. Interpretation of these studies
requires caution, given the abundance of potential confounding factors.
Annuloplasty is seldom performed in isolation and outcomes depend heavily on
concomitant leaflet and/or subvalvular repairs and, in nearly all tricuspid
repairs, on concomitant left sided valve repair or replacement. Even across
otherwise identical surgeries with the same annuloplasty device, variation in
surgeon sizing and/or suturing of the device can be the difference between an
uncomplicated repair and one followed by excessive residual regurgitation,
valvular stenosis, device dehiscence or mitral systolic anterior motion (SAM).
Given these considerations and the lack of large, multicenter randomized trials
comparing standardized surgical repair protocols, the reported differences in
outcomes across annuloplasty devices have not been large enough or consistent
enough to generate consensus guidance for use of particular annuloplasty device
types for particular repair indications.

The goal of the ARB-PMCF study is to evaluate the safety and performance of
Abbott annuloplasty devices used in the surgical repair of mitral and tricuspid
regurgitation for five years from implantation.

The ARB-PMCF study aims to meet the EU Medical Device Directives (MDD)
requirements for clinical follow-up, post-marketing of the medical devices
(PMCF).

The MDD requires equipment manufacturers to perform a PMCF study to confirm the
clinical performance and safety over the expected lifespan of the medical
device and acceptability of identified risks, and to detect emerging risks
based on factual evidence.
ure.

The ARB-PMCF Study has a multicenter, observational, parallel group design in
which 550 subjects will be prospectively followed through five years after
implant of an Abbott annuloplasty device in five treatment groups:

Group 1. Primary mitral disease repair (N=200) with the Rigid Saddle Ring,
Séguin Ring or full Tailor Ring, without cut zone removal, including at
least 50 implants of each ring model.
Group 2. Secondary mitral disease repair (N=200) with the Rigid Saddle Ring,
Séguin Ring or full Tailor Ring, without cut zone removal, including
at least 50 implants of each ring model.
Group 3. Primary tricuspid disease repair with the full Tailor Ring without cut
zone removal (N=50).
Group 4. Secondary tricuspid disease repair with the full Tailor Ring without
cut zone removal (N=50).
Group 5. Primary tricuspid disease repair with the Tailor Band or partial
Tailor Ring with the cut zone removed (N=50).

This investigation has an observational design in which nearly all data
collected are from examinations, imaging, medical treatments and procedures
that would have occurred in the absence of the investigation. In these
instances, participation in the investigation poses no additional risk beyond
what subjects would incur under the usual standard of care.

The investigation includes required TTE at the one-year, three-year and
five-year visits which do not coincide with the usual standard of care. TTE has
no known risks beyond the discomfort associated with having an ultrasound probe
pressed against the skin of the chest and upper abdomen. Blood draws for
hepatic and renal function panels are required for subjects in Groups 3 and 4.
There are minor risks associated with collection of blood, including discomfort
from the needle stick, a small risk of infection, bruising, swelling, bleeding
or fainting. These risks are minimized by having a qualified person perform
blood collection, adherence to aseptic technique and appropriate disinfection
of the venipuncture site before needle insertion.

The burden for the subjects is that the one-year, three-year and five-year
visits will have to be performed in the hospital and are not part of the
standard of care. At the two-year and four-year visit there will be a phonecall
with the researchteam, which is not part of the standard of care. Therefore the
burden of participation consists of the additional time and additional
procedures from the follow-up visits.