Intraprocedural mitral regurgitation and gradient: key determinants of transcatheter edge-to-edge repair outcomes for primary mitral regurgitation

Transcatheter edge-to-edge repair (TEER) has emerged as a crucial therapeutic option for patients with degenerative mitral regurgitation (MR) who are at high or prohibitive risk for surgical mitral valve repair. TEER has gained prominence due to its minimally invasive nature, which significantly reduces the risk associated with traditional surgical approaches, particularly in elderly and/or high-risk patients. The success of TEER largely depends on the degree of residual mitral regurgitation (rMR) and the mean mitral pressure gradient (MPG) following the procedure, as these factors significantly influence long-term clinical outcomes. The study titled “Impact of Intraprocedural Mitral Regurgitation and Gradient Following Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation” investigates the prognostic implications of intraprocedural rMR and mean MPG in patients undergoing TEER for primary MR (1). Using data from the PRIME-MR registry, which included 1,509 patients from 27 international sites, the study categorizes patients based on rMR (optimal result: ≤1+, suboptimal result: ≥2+) and MPG (low gradient: ≤5 mmHg, high gradient: >5 mmHg) to evaluate their individual and combined impact on two-year outcomes, specifically all-cause mortality and heart failure hospitalization.

Key findings reveal that intraprocedural rMR is a strong independent predictor of adverse clinical outcomes, with higher event rates observed in patients with suboptimal rMR (≥2+). Interestingly, MPG itself was not found to be an independent predictor of outcomes, suggesting that it is essential to focus on achievement of maximal rMR reduction during TEER and if necessary, may accept higher transvalvular gradient to enhance long-term clinical outcomes. The results of this study provide additional insights for clinicians regarding procedural endpoint of TEER as the treatment of degenerative MR, highlighting the need to balance rMR reduction and concomitant mean MPG increase for optimal clinical outcomes.

rMR: a key determinant of outcomes

The findings of this study add further supportive evidence to the growing body of literature emphasizing the importance of achieving minimal residual MR during TEER. The impressive incremental separation of Kaplan-Meier curves presented Fig. 4A of Ludwig et al.’s study, based on rMR degree from no or mild, moderate, to moderate-to-severe or severe for combined endpoint of mortality and hospitalization further reaffirms importance of lowering rMR during a TEER procedure to achieve optimal clinical outcomes.

Residual MR has consistently been a critical determinant of long-term outcomes in patients with symptomatic MR undergoing the TEER regardless of its etiology. Makkar et al.’s study on TEER for primary MR similarly found that achieving a better reduction in residual MR significantly improved patient outcomes, echoing the results of the current study (2). The COAPT trial that enrolled functional MR demonstrated that patients with minimal residual MR post-TEER had significantly better outcomes compared to those with higher levels of residual MR (3). The COAPT trial underscored that reducing MR to an optimal level (≤1+) is associated with improved survival and fewer heart failure hospitalizations. Additionally, the OCEAN-Mitral Registry demonstrated that moderate residual MR (2+) at discharge leads to worse clinical outcomes, including increased mortality and heart failure hospitalizations, compared to those with mild or no residual MR (4). The consistency across these studies underscores the pivotal role of minimizing residual MR to enhance long-term prognosis across different patient populations regardless of MR etiology.

Mean pressure gradient

Although the importance of reducing rMR is increasingly recognized, the clinical impact of post TEER mitral MPG remains an area of ongoing debate. Contrary to the current study findings, previous study suggested that adding additional clips may contribute to an increase in post-procedural MPG, which has been associated with worse clinical outcomes, particularly when MPG exceeds certain thresholds (5). Patzelt et al. also reported that in addition to a degree rMR reduction, an elevated MPG (>4.4 mmHg) is independently predictive of adverse clinical outcomes in patients with degenerative MR following TEER (6). Their sample size is relatively small and also the results could be affected by selection bias. On the contrary, Yoon et al. found that in primary MR patients undergoing TEER, post procedural elevated MPG was not independently associated with adverse outcomes (7). One factor that should be noted is that the degree of MPG elevation post TEER in majority of reported papers is probably at the worst, moderate and may not reach the real threshold to cause immediate unfavorable hemodynamic and clinical outcomes itself. Leaving significant mitral stenosis even with outstanding rMR reduction is generally unacceptable and TEER should be aborted without releasing the treatment device.

Still, in the current study, a presence of elevated MPG appears to indirectly impact on the worse clinical outcomes in association with the degree of rMR reduction. In four groups comparison, this study clearly demonstrated that the group with suboptimal rMR reduction/elevated MPG has the worst clinical outcomes compared to the rest of groups including that with suboptimal rMR reduction/low MPG. Moreover, the better clinical outcome was seen in the group with optimal rMR reduction/low MPG compared to that with optimal rMR reduction/elevated MPG. A similar trend of results was also reported in the previous study including the larger cohort by Makkar et al. (2). In their study, rMR reduction with maintaining a low MPG in patients with primary MR was associated with the best improved 1-year survival following TEER. The mean MPG observed in the optimal result/high gradient group (6.7±1.1 mmHg) and the suboptimal result/high gradient group (7.0±1.3 mmHg) fall within ranges typically associated with moderate mitral stenosis. Although such gradients may be clinically tolerable in specific cases, markedly higher gradients could potentially lead to adverse hemodynamic consequences and worse clinical outcomes. To ensure optimal decision-making, MPG should be interpreted in the context of individual patient characteristics, including their hemodynamic state and clinical presentation, with careful attention to balancing procedural success and potential risks.

Intraprocedural endpoints toward the best follow-up outcomes

As opposed to multiple published studies using rMR and/or MPG obtained at the discharge or at the 30 days post-procedure, the current study used intraprocedural rMR and MPG acquired by TEE on the TEER device release to investigate their impact on follow-up outcomes. The study’s focus on utilizing these “intraprocedural” parameters and demonstration of their long-term prognostic impact further support validation of appropriate procedural endpoint using them to optimize individualized TEER outcomes. However, the observational nature of the study introduces potential biases, and the lack of core lab adjudication of echocardiographic data may impact the consistency of rMR and MPG measurements. Additionally, as intraprocedural MPG measured during TEE often differ from post-implant gradients assessed under different hemodynamic conditions, the absence of post-implant echocardiographic data limits the direct correlation between intraprocedural findings and long-term outcomes. Achievement of rMR reduction ≤1+ should be a specific and primary optimal target goal of TEER as the significant residual MR has detrimental impact on long-term outcomes (8). If this is difficult to achieve, the next target goal can be set up using hierarchical threshold combined rMR and MPG. This approach may be particularly valuable in consideration of additional device use. For instance, if the first TEER device leads to moderate MR reduction without MPG increase, as far as anatomically feasible, using additional TEER device will likely achieve optimal treatment goal with less impact on MPG. However, if the first TEER device increases MPG significantly without meaningful MR improvement, the TEER may not be feasible, the procedure should be aborted and alternative treatment such as MV replacement may have to be pursued. Lastly, if optimal MR reduction ≤1+ is achieved with moderate increase of MPG, this could be still acceptable in selective cases depending on individual’s clinical background, a goal of care and accessibility to alternative treatment options, since benefits of MR reduction during follow-up period seems to overweigh a negative impact of immediate MPG increase after TEER. In the current study, the group with optimal rMR reduction/elevated MPG has the second-best follow-up outcomes after the group with optimal rMR reduction/low MPG. Overall, the current study adds further supportive data from a practical standpoint, how to utilize these intraprocedural parameters to determine optimal and individual procedural endpoint with consideration of balancing rMR and mitral MPG after TEER.

Conclusions

This study reinforces the importance of optimal reduction of rMR during TEER to enhance patient outcomes, aligning with previously reported findings. The impact of residual mitral MPG remains debated, with its impact varying across different patient subset. Future research should aim to clarify this issue, since formulation of personalized strategies will be crucial for ensuring long-term success across diverse populations.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Cardiovascular Diagnosis and Therapy. The article has undergone external peer review.

Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-491/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-491/coif). The authors have no conflicts of interest to declare.

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