Prof Manuel J Antunes
Faculty of Medicine,
University of Coimbra,
3000-548 COIMBRA
Portugal
Tel +351-962092677
e-mail: mjantunes@fmed.uc.pt
ABSTRACT
The MitraClip technique has been increasingly used for correction of
mitral valve regurgitation in patients in whom surgical mitral repair is
considered contraindicated or very risky, but off label use occurs
often. Failure of the procedure, translated into moderate to severe
rates of residual or recurrent mitral regurgitation, is observed in up
to one-third of the patients, and surgery has been used to correct it in
a number of cases, in what can be called an “operation for the
inoperable”. That is precisely the subtitle of a paper published in
this issue of the JOCS by Gerfen and colleagues, who analyse their
institutional experience with a series of 17 patients. In this
Editorial, I comment on this series and the possible reasons for failure
of the MitraClip, and on the indications for reintervention and its
constraints, which I hope can contribute to the discussion about
“further exploration and refinement of patient selection criteria and
identify predictors for MitraClip failure”, as the authors suggest.
The percutaneous edge-to-edge mitral valve repair, MitraClip procedure,
for treatment of mitral valve regurgitation was introduced almost two
decades ago (first case in 2003) as an alternative to surgical repair in
patients who were not suitable for surgery.[1] It is based on the
Alfieri technique, which consists of a stitch used to unite prolapsing
segments of the two mitral valve leaflets.[2] But there are major
differences between the two methods: Firstly, while the MitraClip is
essentially a ‘blind’ procedure, even when guided by transesophageal
echocardiography or any other image method, performed with the heart
beating, the Alfieri stitch is placed under direct vision by the
surgeon, even when minimally invasive methods are used, with a quiet
heart, thus permitting precise positioning of the stitch. This blindness
effect of the percutaneous method is translated into the need for
multiple clip usage in the majority of cases. Thus, the incidence of
failure is bound to be higher in the MitraClip procedure. On the other
hand, it has been shown that the Alfieri technique fails mostly when it
is not accompanied by some type of valve annuloplasty,[3] but all
methods of percutaneous mitral annuloplasty have, so far, proven very
insufficient.
Because of these shortcomings, and contrary to other methods of
percutaneous valve procedures, especially aortic valve implantation
(TAVI), the current guidelines still restrict the use of the MitraClip
to patients in whom surgery is considered contraindicated or associated
to a very high risk.[4,5] Which raises the question of subsequent
surgery in the cases of early or late clip failure, especially in
emergency situations, i.e., an “operation for the inoperable”.
This is precisely the subtitle of a paper published in this issue of the
Journal by Gerfen and colleagues from Cologne, Germany,[6] in which
the authors describe a retrospective single-center cohort study of 17
patients requiring mitral valve surgery after failure of the MitraClip
procedure. This series is constituted by a high-risk (mean EuroSCORE II
= 10), very symptomatic patient population with persistent or severe
recurrent mitral valve regurgitation, which was mainly caused by
detachment or dislocation of the clip. These patients required complex
reoperations with the need for concomitant surgeries. In-hospital and
30-day all-cause mortality were 12% and 18%, respectively, and there
were high rates of prolonged mechanical ventilation and ICU stay. Hence,
the authors concluded that “failure of MitraClip represents a
challenging situation limited by high-risk profiles of patients and
limits the possibility of surgical valve repair, shown by a high rate of
mitral valve replacement… therefore, a careful evaluation of
patients undergoing MitraClip is of paramount importance”.
In this work, the population demographics is well characterized in the
three phases, before and during MitraClip application, and before
surgery, but it would be of interest to know what was the overall
incidence of surgery after MitraClip in the authors’ institution and how
does that compare with other reports. Also, how many patients would be
candidates for surgery but did not reach it, for whatever reason.
Considering that urgent or emergency operation was undertaken in 65% of
the cases and that in 47% it was a re-operation, peri and postoperative
outcomes were quite good for this type of population, perhaps showing
that refusal for surgery in the first place may not have always been
appropriate.
This is a unique paper, as only limited experiences have been reported
so far. We are talking about patients in whom surgery was initially
refused because of unacceptable risk, and I agree with the second part
of the conclusions about the need for careful evaluation of patients
both before and after insertion of the MitraClip. Papers like the
current one are important because these types of complications, which
are not that rare, are usually not given sufficient relevance in
publications describing the experience with this and other innovative
methods, even in those resulting from large clinical trials. They should
serve to dampen some extensive, say exaggerated, enthusiasm surrounding
these experiments, especially in their early phase.
We are aware that in many places around the world, the MitraClip is used
off-label and in clear ‘disobedience’ to the guidelines produced by the
most important cardiac and surgical societies on both sides of the
Atlantic. [4,5] The ESC/EACTS 2021 Guidelines indicate that in
primary mitral regurgitation the MitraClip procedure ”may be considered
(class IIb) in symptomatic patients who fulfil the echocardiographic
criteria of eligibility, are judged inoperable or at high surgical risk
by the Heart Team and for whom the procedure is not considered futile”.
On the other hand, the 2020 American Guidelines give it a IIa (is
reasonable) indication for similar inoperable or high risk patients with
secondary mitral regurgitation.
But patients are increasingly being attracted to the procedure because
of its perceived ‘much less-invasiveness’ nature and faster recovery. In
my opinion, however, not everything that is done without an open chest
is necessarily good for the patient. And I include here some abusive use
of minimally invasive cardiac surgery procedures.
One other important consideration is the fact that use of the MitraClip
generally limits the possibility of subsequent surgical valve repair,
shown by Gerfen and colleagues’[6] high rate (94%) of mitral valve
replacement, that confirms other authors’ experience.[6] That’s why
valves amenable to surgical repair, should have had that option
considered initially. It is not possible to evaluate the precise
clinical situation of the 17 patients at the time when the percutaneous
procedure was undertaken. Also, the classification of “high surgical
risk” is very subjective. We are often ‘forced’ to operate on high
surgical risk patients, surprisingly with good or excellent results.
Besides, it is well known that the commonly used scores overestimate
operation risk.[8]
Therefore, I believe that this is an area of endeavor where
comprehensive preoperative evaluation by the Heart Team is of absolute
importance, as recommended in the guidelines. As the authors state, the
current study can “contribute to further exploration and refinement of
patient selection criteria and identify predictors for MitraClip
failure”.
A final consideration: the current definition of procedural success for
MitraClip therapy dates to the EVEREST-1 trial and includes
“implantation of at least one clip and achievement of a residual mitral
insufficiency ≤2+”.[9] However, it has now been well demonstrated
that residual 2+ mitral regurgitation, which occurs in about one third
of the cases after MitraClip implantation, was associated with worse
follow-up outcomes.[10] In surgical interventions, on the other
hand, immediate success is generally only considered when the severity
of residual mitral insufficiency does not exceed 1+, and immediate steps
to correct more severe degrees of regurgitation are recommended during
the same procedure.
And this is no minor difference!