Mechanical intervention of FMR: the game changers
Although long-term outcomes of surgical repair for primary MR have been
excellent, treatment for FMR with valve repair or replacement has
produced less favorable results. Both US and European guidelines
currently recommend medical therapy as the initial strategy and mainstay
of FMR management with CRT and revascularization as
appropriate.7-9 In the 2017 American College of
Cardiology/American Heart Association (ACC/AHA) valvular guidelines, the
biggest change was a new recommendation that “it is reasonable to
choose chordal-sparing MV replacement over downsized annuloplasty repair
if an operation is considered for severely symptomatic patients (New
York Heart Association (NYHA) class III-IV) with chronic severe ischemic
MR (stage D) and persistent symptoms despite GDMT”.8This was based on remarkable findings of a cardiothoracic surgical
trials network (CTSN) multicenter RCT showing that the recurrence rate
of moderate-to-severe MR over 1 and 2 years was significantly higher in
the restrictive annuloplasty repair group than in the replacement group,
associated with a higher incidence of HF and
rehospitalization.11,12 In addition, the
recommendation for MV repair in patients with chronic, moderate ischemic
MR undergoing coronary artery bypass grafting (CABG) changed from “may
be considered” to “usefulness of MV repair is uncertain” (2b, Level
B-R).8 This modification was largely based on another
CTSN study demonstrating that the addition of restrictive MV
annuloplasty to CABG did not add any survival benefit or reduce overall
adverse events or readmissions.13,14 A superficial
interpretation of these two CTSN trials favors replacement in patients
with severe FMR. For moderate FMR, leaving it alone at the time of CABG
seems to be reasonable.
The reality of the poor prognosis despite rigorous GDMT (and CRT when
indicated) and the high proportion of advanced HF patients who are too
risky or unsuitable for conventional surgery have stimulated rapid
development of less-invasive transcatheter technologies. Currently, the
most widely used TMVr device is the MitraClip (Abbott Vascular, Santa
Clara, California). This transcatheter intervention produces an
edge-to-edge leaflet coaptation and creates a double-orifice
MV.44 The efficacy and safety of Mitraclip for
moderate-to-severe FMR were evaluated in 2 large RCTs: MITRA-FR
(Percutaneous Repair with the MitraClip Device for Severe
Functional/Secondary Mitral Regurgitation) and COAPT (Cardiovascular
Outcomes Assessment of the MitraClip Percutaneous
Therapy).15,16 Both trials randomized patients to
MitraClip along with GDMT vs. GDMT alone. The MITRA-FR trial found no
differences in a composite of death from any cause and readmissions for
HF at 1 year, while the COAPT trial found a significant reduction in
hospital readmissions for HF at 2 years and overall mortality. On the
basis of the results of the COAPT trial, the FDA approved the MitraClip
for the treatment of FMR in patients with HF who remain symptomatic
despite GDMT.9 Consequently, new changes have been
made in the most recently published “2020 Focused update of the 2017
ACC expert consensus decision pathway on the management of mitral
regurgitation”,9 which supported the consideration of
TMVr in the management of FMR.
However, the strikingly opposed findings across the 2 MitraClip RCTs,
which used precisely the same device to reduce MR, have generated
intense debate because these results cannot be simply explained by
differences in trial design, length of follow-up, or statistical
power.37 Intriguingly, an examination of the baseline
characteristics of the patients participating in the 2 trials indicated
that the studies included 2 distinctly different populations of patients
with FMR.45,46 Patients enrolled in the COAPT trial
had more severe FMR (EROA 41mm2 vs.
31mm2; RVol 60ml vs. 45ml) and less dilated ventricles
(LVEDV index 101ml/m2 vs. 135ml/m2)
than those in the MITRA-FR trial. According to the concepts of
proportionate and disproportionate MR, it is evident that the patients
in the MITRA-FR trial represent a population in which the MR is
proportional to the ventricular dilatation and is a consequence, not a
cause, of the ventricular disease. Therefore, these patients would
generally respond favorably with an improved prognosis when treated with
GDMT aiming at reducing the ventricular volume. In contrast, the
patients in the COAPT trial had disproportionate degrees of FMR, with
higher RVol for smaller ventricles, in which proper functioning of the
MV apparatus is disproportionately undermined, leading to severe MR that
cannot be explained by the degree of LV enlargement. These patients
would be ideal candidates for mechanical interventions aimed at
correcting the MR.37-39
Hence, the outcomes of recent surgical and transcatheter RCTs emphasized
the importance of patient selection and, taken together, have delineated
the beneficial role of MV intervention in FMR patients who have
disproportionate regurgitation despite GDMT (or CRT when indicated).
Concurrently, the effectiveness of MV intervention in patients with
proportionate or non-severe MR is yet to be proven.47