Persistent Tricuspid Regurgitation Despite Mitral Transcatheter Edge-to-Edge Repair: Anticipate Early, Reassess Closely

Significant tricuspid regurgitation (TR) frequently coexists with severe mitral regurgitation (MR), particularly in patients with ischemic or dilated cardiopathy and functional or secondary valvular diseases, where up to half of patients may present with at least moderate TR.^1,2 Beyond being a simple epiphenomenon, TR is a strong marker of adverse prognosis, with mortality increasing in parallel with its severity.^3,4 Current guidelines recommend concomitant tricuspid valve intervention at the time of mitral valve surgery when TR is severe, and to a lesser extent when TR is moderate (respectively class IB and class IIaB in European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines).⁵ Transcatheter therapies have shifted this paradigm by enabling staged interventions. Indeed, mitral transcatheter edge-to-edge repair (M-TEER) may reduce pulmonary pressures and potentially improve TR, allowing subsequent consideration of tricuspid valve intervention only in cases of persistent TR. This raises key clinical questions: which patients are likely to have persistent TR after M-TEER, how does persistent TR affect outcomes, and should these findings support a staged or a more integrated mitral–tricuspid treatment strategy?

In this issue of Structural Heart, Kühlein et al.⁶ provide insights from a large dual-center cohort of 905 patients undergoing M-TEER, with echocardiographic follow-up available in 454 patients (50.2%). Persistent severe TR was observed in 16.3% of patients at 3 months and was associated with significantly increased mortality. A key strength of the study is the integration of transcatheter tricuspid valve intervention (TTVI) eligibility as a composite of severe or greater TR (TR grade ≥ III), systolic pulmonary artery pressure <70 mmHg (indicating absence of severe pulmonary hypertension), no persistent severe MR (MR < grade III), left ventricular (LV) ejection fraction (LVEF) > 30% and tricuspid annular plane systolic excursion >10 mm. This approach reveals a striking divergence in outcomes: patients with persistent TR who were TTVI-eligible had survival comparable to those without severe TR, whereas TTVI-ineligible patients had markedly reduced survival (approximately 40% at 2 years). The study also reinforces 2 important prognostic signals: baseline TR severity and the persistence of severe TR after M-TEER are both independently associated with mortality. In addition, predictors of TR persistence include right heart remodeling (right ventricle [RV] and right atrium dilation), baseline TR severity, LVEF, and female sex, factors that may help anticipate which patients are unlikely to experience TR regression. Finally, the study shows that although left-sided hemodynamics improve after M-TEER, RV reverse remodeling is limited, supporting the concept that TR persistence reflects advanced and often irreversible right heart disease.

Several important limitations and conceptual issues should be highlighted. First, the most important limitation is the incomplete follow-up. Only half of the original cohort underwent 3-month follow-up echocardiography, and those who did not had a worse clinical profile and experienced higher mortality. This is not merely a methodological issue; it is also a clinical warning. A sequential strategy depends on reliable reassessment. If 50% of patients are lost to follow-up after M-TEER, especially if those patients are frailer or more advanced, the staged approach may miss the very patients most likely to deteriorate. Second, no patient underwent TTVI in this cohort, even when classified as eligible. Therefore, TTVI eligibility should not be interpreted as evidence that TTVI improves survival in this setting. Rather, eligibility appears to function as a surrogate marker of disease severity. The observed survival advantage among eligible patients reflects lower disease severity, not a treatment effect. Third, the criteria used to define TTVI eligibility deserve discussion. Some of these thresholds originate from surgical reasoning or from trial selection criteria rather than from validated transcatheter-specific contraindications. In surgery, severe LV dysfunction, severe RV dysfunction, and pulmonary hypertension are major determinants of operative risk. In contrast, for TTVI, guideline-based exclusion criteria are more limited, with severe RV dysfunction and precapillary pulmonary hypertension being the principal factors highlighted in current European Society of Cardiology/European Association for Cardio-Thoracic Surgery recommendations.⁵ Thus, severe LV dysfunction is not, in itself, a formal contraindication to TTVI, but rather reflects advanced disease and may attenuate the benefit of intervention, as suggested by findings from the TRIGISTRY registry.⁷ In that regard, it is important to highlight that the authors evaluated clinical rather than anatomical eligibility. Fourth, the study does not address the role of concomitant mitral–tricuspid transcatheter procedures. It remains unclear whether such strategies were performed in these centers and in what proportion. This is highly relevant, as the study indirectly supports a staged approach but does not compare it with a combined strategy. Fifth, additional predictors of TR persistence may not have been fully captured. These include specific etiologies such as rheumatic disease or cardiac implantable electronic device–related TR, the presence of moderate TR at baseline, and, importantly, the lack of distinction between atrial and ventricular functional MR and TR. This distinction represents a relevant limitation, as these phenotypes differ in underlying mechanisms, remodeling patterns, reversibility, and likely response to M-TEER. Sixth, the quality of mitral repair deserves more attention. Residual MR was uncommon but not negligible. Since residual MR can sustain pulmonary hypertension and limit TR regression, procedural success of M-TEER is a key determinant of TR evolution and a potential confounder. Seventh, the small sample size of the key subgroup is a major limitation. Only 74 patients had persistent severe TR, including 51 TTVI-eligible and 23 TTVI-ineligible patients. This limits statistical power and the robustness of subgroup comparisons. Eighth, the lack of medical therapy data (e.g., diuretics, heart failure therapies) may confound both TR evolution and outcomes.

Perspectives

This study highlights the need for a more proactive and integrated approach to mitral–tricuspid disease. The key challenge is to identify, before M-TEER, patients at high risk of persistent TR. Factors such as baseline TR severity, RV and right atrial dilation, pulmonary hypertension, LVEF, and cardiac implantable electronic device presence should be integrated into a preprocedural assessment.⁸ This could help guide strategy selection, with a combined approach in patients with advanced right heart remodeling and a high likelihood of TR persistence, and a staged approach in patients with potentially reversible disease. Importantly, the results also challenge the “fire-and-forget” concept of M-TEER. Correction of MR does not guarantee right-sided recovery, and the absence of RV reverse remodeling suggests that the window for intervention may be limited. This underscores the need for close early follow-up after the procedure, followed by regular long-term echocardiographic surveillance, as TR may persist or progress over time.⁹ Future studies should compare concomitant versus staged transcatheter strategies and define TTVI eligibility criteria specific to transcatheter therapies. Ultimately, whether patients with severe MR and TR, particularly when both are secondary and ventricular in nature, should be considered for intervention remains open to debate.

Conclusion

Kühlein et al. provide important insights into the prognostic significance of persistent TR after M-TEER, highlighting that outcomes are not determined by TR severity alone but by the disease stage. However, in the absence of tricuspid intervention in this cohort, TTVI eligibility should be interpreted as a marker of disease stage rather than evidence of treatment benefit. In addition, the high rate of incomplete follow-up raises concerns regarding the feasibility and safety of a purely sequential strategy in routine practice. These findings emphasize the need to move from a reactive to a more anticipatory and holistic approach. Whether a staged or combined intervention should be performed is probably of less relevance and impact than ensuring a planned and careful follow-up after mitral valve intervention, particularly in patients with advanced-stage disease. Ultimately, optimizing outcomes will depend on timely intervention before right heart remodeling becomes irreversible.

Funding

The authors have no funding to report.

Disclosure Statement

David Messika-Zeitoun received unrestricted research grants from Edwards Lifesciences. Julien Dreyfus has received consulting or proctoring fees from Abbott and Edwards Lifesciences.