Role of surgical repair in FMR
The current role of surgical repair in FMR appears limited due to the
conservative recommendations given by the 2017 U.S. and European
guidelines and the position papers of professional
societies,7,8,46 which are predominantly based on the
results of 2 CTSN randomized studies.7,8,12,14Observational, non-randomized, and single-center experiences often lack
robustness in study design with non-rigorous definitions of the degree
of MR especially in patients with moderate and severe
MR.48 Although RCTs are less susceptible to
confounders and non-homogeneity of the samples, insufficient power and
methodological or operational flaws might fail to generate evidence that
can reliably be used to guide patient care.41
In the CTSN moderate IMR trial, the negative results after 2-year
follow-up might be reasonably explained by the novel conceptual
framework that all the enrolled patients were presented with
proportionate MR (EROA of 0.2±0.1 cm2 and LV
end-systolic volume index (LVESVI) of
54.8±24.9ml/m2).13,14 The
contribution of CABG targeting ischemic ventricular muscles, not the
restrictive annuloplasty targeting at mitral annulus, for alleviating MR
is fundamental, and the results show that adding MR correction
procedures to CABG showed no additional benefit in death and major
adverse events.14 However, several flaws in this trial
should be noted. Firstly, given the fact that 35.8% of patients in the
CABG only group and 31.3% in the combined procedure group had no AMI,
mixing patients with myocardial ischemia and infarction made the results
inconsistent because pure IMR is reversible with revascularization and
MR secondary to infarction-induced LV remodeling responds poorly to
CABG;49 Secondly, the gradation of severity of IMR as
moderate (EROA 0.20-0.39 cm2, vena contracta 0.3-0.69
cm and color Doppler jet area from 20% to 40% of the left atrial area)
in this study now have been defined as severe in 2017 European
guideline.7 As a result, these discrepancies cast
shadow on the way the study was built and on its conclusions. Moreover,
whether a survival benefit beyond 2 years in adding MV repair to CABG
could be translated from better cardiac physical function, less IMR
grade and higher reverse LV remodeling observed during 2-years follow-up
is pending.14 Therefore, the impact of surgical MV
repair in moderate IMR remains to be re-evaluated.
In the CTSN severe IMR trial, although a substantially recurrence of at
least moderate MR developed in 58.8% of the patients in the repair
group, the patients who did not have recurrent MR had greater LV reverse
remodeling than patients who underwent replacement (LVESVI 42.7±26.4ml
vs. 60.6±39.0ml) at 2 years.12 This outcome validates
the well-proven principle that a “good repair” (with durable
correction of MR) outperforms the best replacement in the setting of
FMR.50 However, the high prevalence of recurrent MR in
this cohort of patients contrasts with apparent durability of the same
restrictive annuloplasty in patients with moderate MR (11.2%) studied
by the same group of investigators.14 It is logically
to attribute these differences to the larger LV in patients with severe
MR. However, baseline LVESVI were only modestly greater in patients with
severe MR (61.1±26.2 ml/m2)12 than in those with
moderate MR (59.6±25.7 ml/m2).14 More importantly,
among patients with severe MR, preoperative LV cavity size was not
different between those who did or did not develop recurrent MR.
Therefore, several authors have suggested the recurrence of MR was most
likely related to a mismatch between LV end-systolic dimension (LVESD)
and the mitral ring size. If the PMs remain laterally displaced relative
to the mitral ring, tethering of the posterior leaflet can be
exacerbated following restrictive annuloplasty.51,52 A
post-hoc analysis by the CTSN authors indicated that a LVESD/ring size
ratio >2 was associated with increased risk of persistent
or recurrent IMR.51 Recent echocardiography-based
studies have identified several valvular (e.g., coaptation depth
>1.5 cm, posterior mitral leaflet angle >45°,
distal anterior mitral leaflet angle >25°, systolic tenting
area >2.5cm2) and ventricular (e.g.,
LVEDV >65mm, coaptation depth >1.5 cm,
end-systolic interpapillary muscle distance >20 mm, and
systolic specificity index >0.7) determinants failure of
undersized annuloplasty in those with FMR.48,53 Given
that these factors were not considered as inclusion or exclusion
criteria for randomization, a crucial bias exists.50If these cases and those with a mismatch between the LV and mitral ring
size were detected at the time of surgery, consideration should be given
to an intervention directed to improving leaflet coaptation at valvular
(e.g., leaflet augmentation plus true-size
annuloplasty,[17,54] Figures 1 and 2) and
subvalvular levels (e.g., papillary muscle approximation or relocation)[55,56]. Since the life-expectancy of patients
undergoing replacement is endangered by the incremental risk of
thromboembolic/hemorrhagic and prostheses-related events, well-designed
RCTs without significant operational flaws are required to reconfirm the
role of surgical MV repair in treating severe FMR.
In the era of fast-evolving transcatheter therapy, apart from the
MitraClip, many other transcatheter devices designed to imitate surgical
repairing techniques, including direct or indirect annuloplasty, have
already been shown to be promising in reducing MR in experimental or
ongoing clinical trials. Further studies will determine whether selected
FMR patients (with or without different risk profile and predictors of
repair failure) might benefit from tailored surgical or transcatheter
repair.