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Spieker et al. Vessel Plus 2020;4:29 I http://dx.doi.org/10.20517/2574-1209.2020.28 Page 9 of 11

Effects of MitraClip implantation on dynamic MR
At one-year follow-up, MitraClip implantation was associated with reduction in symptoms as assessed by
NYHA functional class and improvement in MR severity as assessed by echocardiography. Our findings are
[8]
in line with the results from the EVEREST-II trial, supporting MitraClip therapy mainly in primary MR ,
as well as with the results from real-world registries deciphering clinical improvement in patients with
[9]
predominately secondary MR . Notably, there was a similar clinical benefit (regarding all-cause mortality,
hospitalization for heart failure and reduction of NYHA functional class) and no difference in reduction of
MR severity in patients with dynamic severe MR compared to patients with severe MR already at rest.

Our findings here support the performance of exercise echocardiography in patients displaying moderate
MR at rest but reporting high-grade MR from a previous echocardiography or presenting with symptoms
[10]
suggestive of dynamic MR. Recently, Van de Heyning et al. provided the first clinical evidence of
hemodynamic improvements during exercise following PMVR in patients with secondary MR. They
compared exercise echocardiography before and six months after MitraClip implantation. In 31 patients, a
significant reduction of MR at peak exercise along with increased calculated cardiac output and decreased
pulmonary arterial pressures (measured echocardiographically by trans-tricuspid pressure gradient)
was documented. Here, we demonstrated in a larger, all-comers cohort that these findings go along with
reduction in symptoms as assessed by NYHA functional class and an improvement in MR severity. The
findings presented are of clinical relevance because MR resembles a dynamic entity that is sensitive to
[1]
changes in preload, afterload and ventricular geometry as well . Even in patients with only mild or
[11]
moderate MR at rest, Lapu-Bula et al. demonstrated a relevant negative impact on exercise-induced MR
deterioration on exercise capacity. This might have been due to the combination of an inhibition of the
[11]
expected increase in exercise forward stroke volume and a marked increase in pulmonary artery pressure .
[12]
Recently, Lancellotti et al. provided clinical evidence to understand the unfavorable consequences of
dynamic MR. They described that SPAP during exercise is associated with dynamic increase in EROA in
patients with secondary MR and revealed a significant prognostic importance of exercise-induced PH,
regarding the occurrence of cardiac death and cardiac events. The prognostic impact of dynamic MR
has also been described by others [2,6,13] . In this regard, mortality in patients with deteriorating secondary
MR during exercise managed with optimal medical therapy exhibited increased mortality in the range
of patients with severe MR already at rest . In the present study, we demonstrated a similar benefit in
[6]
patients with dynamic severe MR and patients with severe MR at rest with regard to outcomes such as all-
cause mortality, hospitalization for heart failure and symptomatic improvements. This may be explained
by an effective reduction of dynamic MR by PMVR, as optimal reduction of MR seems to be of utmost
importance for long-term clinical outcome . Mechanistically, PMVR with MitraClip implantation
[14]
[15]
effectively increases coaptation area, thus improving closing force efficiency with an additional decrease
[16]
in annular dimensions (antero-posterior) . This may lead to reduction in MR severity not only at rest, but
[10]
also during exercise as has been recently shown by Van de Heyning et al. and is accompanied by relief
from dyspnea.
The role of handgrip echocardiography prior to MitraClip implantation
Our study demonstrates that handgrip exercise serves as a valuable tool to unmask dynamic changes in
MR. According to pre-defined parameters [Supplementary Figure 2], 15 patients (45%) with DMR and
2
24 patients (40%) with FMR revealed a marked increase in MR severity (EROA > 10 mm , RVol > 15 mL)
during handgrip exercise, irrespective of MR severity at rest. These data foster previous results from studies
[17]
reporting dynamic MR during exercise in one-third of patients with DMR and in 30%-50% of cases with
FMR, both ischemic and non-ischemic etiology [18-21] . Increasing MR severity during handgrip exercise is
[22]
exaggerated by the hemodynamic response , which mainly imposes pressure load on the left ventricle
due to an increase in systemic vascular resistance, whereas dynamic exercise predominately results in
[23]
volume overload . We decided to perform handgrip exercise as we included a frail patients cohort (logistic