DISCUSSION:
The major findings of the present study are as follows:
- Intraprocedural MG was found to be a strong predictor for 12-month
mortality (cut-off value: 4.5 mmHg) and adverse functional outcomes
(cut-off value: 3.9 mmHg).
- We found the worst functional outcomes assessed by NYHA functional
class and walk distance as well as the highest 12-months mortality in
patients with persistent MG ≥ 4.5 mmHg at discharge independently from
the MR aetiology followed by in patients with an in-hospital decrease
in MG to values below 4.5 mmHg at discharge.
- LAI (<1.11) was found to be the strongest predictor for
unfavourable intraprocedural MG (>4.5 mmHg) followed by
baseline MG, the number of implanted clips, and central clip
localisation.
Elevated MG following the MitraClip procedure is considered to be
associated with adverse outcomes (20). Therefore, the current guidelines
recommend avoiding an intraprocedural transmitral pressure gradient
above five mmHg (11). On the other hand, some contradicting studies
currently show no relevant association between MG and outcomes after the
MitraClip procedure, particularly in patients with functional MR (6),
(7). Therefore, the effect of MG on outcomes after MitraClip is
ambiguous.
Intraprocedural assessment of mitral inflow patterns and hemodynamics
might be challenging owing to altered mitral geometry, such as the
double- or multi-orifice MVs after transcatheter MV repair.
Additionally, intraprocedurally assessed MG might be altered by
”abnormal” hemodynamic conditions through general anaesthesia or
inotropes. Despite difficulties in MG assessment by using
continuous-wave Doppler in the setting of catheter-based MV repair, it
was proven to be superior over planimetric evaluation of MVA for
stenosis assessment, in a study with 38 patients by Biaggi and
coworkers. They found peri-interventional planimetry to be unacceptably
time-consuming and also to underestimate the MVA due to technical and
acquisition-related issues (18). Accordingly, we used the Doppler-based
assessment of MG in the present study.
A linear relationship between intraprocedural MG >5 mmHg
and decreased functional capacity, as assessed by using the NYHA
functional classification, was demonstrated by Thaden et al. in a cohort
with 90% DMR (n=112) and preserved LV function (mean LV-EF: 50%).
Correlatively, MG at baseline, the number of implanted clips, and
central clip implantation were shown to be independent predictors for
high intraprocedural MG in our study (21).
Neuss et al. found an invasively measured MG >5 mmHg and an
echocardiographically estimated MG >4.4 mmHg to be
independent predictors for all-cause mortality in 268 patients (mean
age: 75 years) with moderately reduced LV-function (mean LV-EF: 39%)
and moderate-to-severe or severe MR, who underwent the MitraClip
procedure (19). Despite some differences in clinical and
echocardiographic characteristics, such as older patients with better
LV-function and a lower FMR rate, their findings support the validity of
our results.
Utsunomiya et al. found a moderate correlation between MG and MVA after
the MitraClip procedure in 97 patients with pre-existing pulmonary
hypertension. Confirmatively, they discovered that intraprocedural MG
predicts adverse outcomes in a cohort of comparable patients (20).
In a monocentric study including 51 elderly patients (mean age: 75
years), Boerlage-van Dijk et al. demonstrated that intraprocedural
assessment of MG systematically underestimates the value compared to
real life. Of note, the authors found no correlation between higher
intraprocedural MG and increased heart failure symptoms at FU (9). In
contrast, we found higher NYHA functional classes and lower six-minute
walk distances at FU, as well as higher one-year mortality in patients
with intraprocedural MG ≥4.5 mmHg, which might be due to the fact that
the majority of patients included in the cited study had FMR (74%), and
mostly suffer from chronic heart failure. This might hamper discerning
persisting advanced heart failure symptoms and symptoms due to elevated
MG at FU - high competing risk. Our cohort comprised a balanced number
of MR etiologies (DMR: 40%, FMR: 42.8%, mixed: 17.2%), which might be
a reason for the divergent finding.
An intraprocedural MG >4.4 mmHg was shown by Patzelt et al.
to be predictive for a combined endpoint consisting of all-cause
mortality, redo procedure, and LVAD implantation after MitraClip only in
patients with DMR, but not with FMR. Moreover, higher intraprocedural MG
was correlated with lower functional capacity at FU in the same study.
The authors found the patient’s age to be the strongest independent
predictor for the combined endpoint followed by residual MR
>II and intraprocedural MG (7). We also found that baseline
MG and central clip implantation are relevant predictors for
unfavourable intraprocedural MG, although we included more patients with
FMR (42.5%) and in more advanced stages of heart failure. We
additionally found a negative influence of elevated intraprocedural MG
on clinical outcomes regardless of MR aetiology.
Itabashi et al. showed that increased dimensions of the MV and the LV
might be accountable for a somewhat lower intraprocedural MG in a
comparable cohort after one-clip implantation (22). Contrary to our
findings, patients with FMR showed a tendency for developing higher
intraprocedural MG in this study, which might be due to smaller annular
dimensions in their study cohort (AP diameter: 32mm vs 38mm).
Of note, MR geometry has a direct influence on the development of
elevated MG. We found LAI to be the strongest predictor for unfavourable
MG after clip deployment. This new parameter, which reflects on the
length of the leaflets in relation to annular dimensions and offers an
adequate geometrical assessment of the MV, was not assessed in all of
the studies cited but seemed to be associated with residual MR, MG, and
outcomes after the MitraClip procedure (14).
Apart from residual MR as a well-known prognostic parameter,
postinterventional MG appears to be an independent predictor for
clinical outcomes despite in-hospital decrease to values below 4.5 mmHg.
It shows a dynamic postinterventional process and is influenced by
various haemodynamic parameters such as blood pressure, heart frequency,
volume condition of the patient, sedation or anaesthesia, haemoglobin,
inotropes. Therefore, its sporadic assessment may lead to under-or
overestimations, which may lead to misinterpretation
intrainterventionally. Understanding of MG dynamics and its predictors
is desirable to get more favourable outcomes after a successful
interventional MR reduction compared to just residual MR based
decision-making. The definite pathomechanism of this clinical entity
stays still unexplained as an encouraging reason for further prospective
multicentric studies. Considering that higher postprocedural MG is
associated with worse outcome, forthcoming procedural and
device/system-related improvements are desirable.