1 Introduction

Mitral regurgitation (MR) is the second most common valvular dysfunction in Europe and a substantial contributor to morbidity and mortality [1-3].

In severe MR, backwards blood flow and increased filling pressures causes pulmonary vein congestions and leads to pulmonary edema as well as postcapillary pulmonary hypertension. Increased right ventricular afterload can in turn cause right ventricular failure and tricuspid regurgitation (TR) which increases central venous pressure. Especially in the presence of low effective stroke volume (SV) due to backwards flow, tissue perfusion is impaired which ultimately causes end organ failure [4].

Mitral transcatheter edge-to-edge repair (M-TEER) is a well-established minimal invasive procedure to treat MR. Multiple studies have demonstrated reduction in all-cause mortality, hospitalization for heart failure and noninferiority to surgery in selected patients suffering from secondary MR. The procedure is also recommended in primary MR with high surgical risk [5-9].

Postinterventional effects on patient hemodynamic parameters like increased SV, increased cardiac output and reduction in systemic vascular resistance have been reported using noninvasive bioimpedance monitoring as well as echocardiography [10, 11].

After successful leaflet grasping, the implant is closed and MR reduced. This can be verified in real time using TOE. If the result is not satisfactory, the implant can be re-opened and leaflet optimization can be carried out to ensure effective MR reduction. In the final step, the device is released from the catheter.

Electrical cardiometry (ICON®, OSYPKA MEDICAL, Berlin, Germany) is a noninvasive method to measure real time hemodynamic parameters like cardiac SV. The validity of this method has been shown in multiple studies and several settings [12-14].

In our study, we implemented real time hemodynamic monitoring using the ICON system in patients undergoing M-TEER and compared cardiac SV to invasive measurements obtained by right heart catheter (RHC) before and after the intervention using the Fick method. The goal is to provide real time feedback on hemodynamic changes after leaflet grasping and approximation. This could help to quantify reduction of MR additionally to echocardiographic imaging and visualize hemodynamic changes to provide better interventional results and improve patient outcome.

2 Materials and Methods

3 Results

3.2 Stroke Volume Increases After M-TEER

Mean SV as measured via RHC increased significantly after successful M-TEER (Table 2). Boxplots showing SV pre and post M-TEER are demonstrated in Figure 1. Assessment of SV pre M-TEER correlated significantly between RHC and ICON (Figure 2A/Table 2). However, the increase in SV measured by RHC could not be detected using the ICON method (Figure 1). Even though absolute SV measured via RHC and ICON did still significantly correlate post M-TEER (Figure 2B/Table 2), change in SV (delta SV) did not (Figure 2C/Table 2). Overall SV measured via ICON was lower than measurements via RHC (Figure 1). Individual patient data on stroke volume measured via the two methods before and after M-TEER are demonstrated in Figure 2D.

TABLE 2. Results of statistical testing.

Variable	Test	Figure	p-value
Delta stroke volume RHC pre versus post M-TEER	Paired t-test	2	0.026
Stroke volume pre M-TEER ICON versus RHC	Pearson's correlation coefficient	3	0.003
Stroke volume post M-TEER ICON versus RHC	Pearson's correlation coefficient	3	0.021
Delta stroke volume ICON versus RHC	Pearson's correlation coefficient	3	0.995
PCWP mean pre versus post M-TEER	Paired t-test	4	0.355
PCWP v-wave pre versus post M-TEER	Wilcoxon signed-rank tests	4	0.151
LA mean pressure pre versus post M-TEER	Wilcoxon signed-rank tests	4	0.917
LA v-wave pre versus post M-TEER	Wilcoxon signed-rank tests	4	0.049
PA mean pressure pre versus post M-TEER	Wilcoxon signed-rank test	4	0.556
3D EROA pre versus post M-TEER	Paired t-test	4	< 0.001
Delta 3D EROA versus delta stroke volume RHC	Pearson's correlation coefficient	S1	0.420

• Note: Significant p-values of test results are displayed in bold.
• Abbreviations: 3D EROA, three-dimensional effective regurgitant orifice area; LA, left atrium; M-TEER, mitral transcatheter edge-to-edge repair; PCWP, pulmonary capillary wedge pressure; PA, pulmonary artery; PA, RHC, right heart catheter.

3.3 Hemodynamic and Echocardiographic Parameters Change After M-TEER

Hemodynamic parameters obtained via RHC changed after successful M-TEER. Mean PCWP (Figure 3A), PCWP v-wave (Figure 3B), mean LA pressure (Figure 3C) and LA v-wave (Figure 3D) all decreased whereas mean PA pressure increased slightly (Figure 3E). Likely due to the relatively small sample size, only the decrease in LA v-wave was statistically significant (Table 2). To investigate echocardiographic success of the procedure, 3D EROA measurements were carried out pre and postinterventionally. As shown in Figure 3F, D EROA was reduced dramatically after successfully M-TEER. This reduction reached statistical significance (Table 2). Interestingly, reduction of EROA did not correlate with increase in SV as measured by RHC (Table 2, Supporting Information S1: Figure 1).

4 Discussion

In the present study we were able to demonstrate that M-TEER has immediate hemodynamic effects in patients presenting with severe MR. Invasively measured SV increased significantly while LA mean pressure, LA v-wave, PCWP mean pressure and PCWP v-wave were all lower in the postprocedural measurement.

Even though significant correlation between initial measurements and postinterventional measurements could be observed, electrical cardiometry appeared to underestimate SV when compared to the gold standard method in this patient collective. However, in our specific setting, reliable readings of relative changes for periinterventional monitoring of “hemodynamic success” would be sufficient.

Unfortunately, electrical cardiometry was not able to detect the increase in SV in the real time, beat-to-beat measurement. The observed increase in SV via the gold standard method was from a mean of 64 mL/beat to 78 mL/beat (18%). While statistically significant, this change might be too subtle to be picked up by electrical cardiometry. However, median signal quality readings provided by the ICON device were at 90% which should be sufficient.

As mentioned above, PCWP mean pressure, PCWP v-wave, LA mean pressure and LA v-wave all decreased after successful M-TEER. Only the increase in LA v-wave reached statistical significance. However, this is likely to be due to the relatively small sample size as all four parameters show a clear trend. Apparently, pulmonary congestions caused by backwards flow secondary to severe MR is immediately relieved after M-TEER in our collective.

In this study, we used 3D EROA as a parameter for echocardiographic success of the M-TEER procedure. Our results show a reduction of mean 3D EROA of 0.65 cm² to 0.1 cm². This not only demonstrated a significant absolute (0.55 cm²) and relative (85%) reduction in EROA but also emphasizes that our collective suffered from very severe MR at the start of the procedure.

Interestingly, the reduction in MR as measured via 3D EROA did not correlate with the increase in SV as measured via RHC (Supporting Information S1: Figure 1). This demonstrates that multiple factors likely play a role in SV changes after M-TEER. Simard et al. were able to show that reduction in mean LA pressure and LA v-wave depends on MR pathophysiology and Markus et al. demonstrated that particularly patients with poor kidney function showed improvement in cardiac output as measured via noninvasive methods after successful M-TEER [11, 18]. This highlights the necessity for a multimodal approach when assessing periprocedural success of M-TEER.

To our knowledge, this is the first study attempting to monitor real time hemodynamic changes during M-TEER. Since both available systems allow for release and re-grasping of mitral valve leaflets, real time hemodynamic monitoring would enable to observe changes of cardiac SV before device release. Unfortunately, electrical cardiometry using the ICON system was not able to pick up changes in SV measured via RHC. However, different systems or software updates could enable hemodynamic guidance during M-TEER which might improves patient outcome.

5 Limitations

Since oxygen consumption was assumed and not actually measured, measurement inaccuracies with the RHC (Fick) method cannot be ruled out. Furthermore, we cannot exclude fluctuation in patient oxygen consumption during deep sedation which could influence calculation of stroke volume. Also, the sample size was relatively small to investigate the secondary endpoints. This is likely the reason why most secondary endpoints did not reach statistical significance despite clear trends.

6 Conclusion

SV as measured via RHC (Fick method) increases significantly after successful M-TEER. Unfortunately, this change was not captured via electrical cardiometry making this method currently unsuitable for beat-to-beat monitoring during M-TEER. Furthermore, a decrease in PCWP mean, PCWP v-wave, LA mean pressure and LA v-wave could be observed.

Ethics Statement

The study complies with the declaration of Helsinki and good clinical practice guidelines and was approved by the responsible local ethics committee (project number 238/2018BO2).

Consent

Written informed consent was obtained in all patients participating in the study.

Conflicts of Interest

The authors declare no conflicts of interest.