Degenerative mitral valve stenosis (DMS) is a complex condition that presents significant challenges in both diagnosis and treatment. It is most commonly associated with mitral annular calcification (MAC), which can extend to the mitral leaflets and subvalvular apparatus. The occurrence of MAC is associated with several atherosclerotic risk factors, including advanced age, female sex, diabetes, smoking, obesity, and chronic kidney disease.1 The reported incidence of MAC varies widely depending on both the age of the population studied and the imaging modality used, occurring in approximately 10% of individuals older than 60 years and increasing to about one-third of those over 90 years.2

Although MAC-related mitral valve dysfunction is the most common complication, moderate to severe mitral regurgitation (MR) is the predominant manifestation, occurring in up to 30% of patients with MAC.1,3 In contrast, significant MS is much less frequent, affecting approximately 8% of patients.1,3 Its pathophysiology differs significantly from that of rheumatic mitral stenosis. Rheumatic disease is characterized by commissural fusion, leaflet thickening and chordal involvement, resulting in a “funnel-shaped” orifice.4 In contrast, DMS is driven by extensive annular and basal leaflet calcification, producing a “tunnel-like” obstruction that usually spares leaflet tips and lacks commissural fusion.4 Consequently, conventional echocardiographic parameters, particularly mitral valve area by planimetry, are less reliable in this setting, and standard interventions such as percutaneous balloon commissurotomy are generally not suitable.5

Because DMS primarily affects elderly patients with multiple comorbidities, surgical intervention is often associated with high operative risk and increased morbidity. Current European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines on Valvular Heart Disease state that transcatheter mitral valve implantation can be considered in highly selected patients with severe MV dysfunction and extensive MAC, provided the procedure is performed in experienced centers.6 Nevertheless, reported outcomes remain suboptimal, with one-year mortality ranging from 10 to 30% even after successful treatment.6 Some patients are not candidates for this therapy due to anatomical features that suggest a high risk of embolization or left ventricular outflow tract (LVOT) obstruction. Together, the limited effectiveness of established therapies and the lack of strong randomized data highlight a significant unmet clinical need in this population.

Lithotripsy-assisted balloon valvuloplasty has recently emerged as a novel percutaneous technique for treating calcific mitral stenosis. Since the first in-human report in 2019,7 small case series have described encouraging short-term clinical and hemodynamic results, demonstrating meaningful reductions in transmitral gradients (TMG) without significant worsening of concomitant MR.8–12

Technical refinements of lithotripsy-assisted balloon valvuloplasty have gradually overcome key procedural limitations, particularly challenges related to stable device positioning and adequate contact with heavily calcified mitral structures, which are essential for effective lithotripsy delivery. The introduction of larger-diameter lithotripsy balloons was instrumental in resolving these issues. Recent case reports have described the use of peripheral 12-mm Shockwave® balloons, which are compatible with 0.018″ support guidewires and deliver two lithotripsy pulses per second, thereby streamlining the procedure.8,13,14 In addition, a dual deflectable sheath strategy has recently been proposed to improve catheter stability and enhance the precision of lithotripsy balloon positioning across the mitral valve.13 At the same time, Giustino et al. reported a small case series using a triple-balloon configuration, which resulted in significant hemodynamic improvement and removed the need for adjunctive noncompliant balloon dilation.14

The aim of our work is to report the feasibility and safety of the first lithotripsy-assisted balloon valvuloplasty cases performed in our center, using a dual deflectable sheath strategy with simultaneous dual-balloon lithotripsy, without adjunctive noncompliant balloon valvuloplasty.

This series adds to the limited but growing body of evidence supporting lithotripsy-assisted balloon valvuloplasty as a potential treatment option for patients with DMS and extensive calcification who are not candidates for surgery or conventional transcatheter therapies. To our knowledge, this represents the first reported national case series using this strategy.

The procedural concept aligns with previously described lithotripsy-based mitral interventions, while incorporating important technical adaptations. Prior reports have demonstrated the feasibility of multi-balloon lithotripsy configurations8–11 and, more recently, the use of a dual steerable sheath strategy to optimize device positioning and stability across the mitral valve.13 Our approach combines dual deflectable sheath support through a single transseptal puncture with simultaneous dual-balloon lithotripsy delivery, while avoiding adjunctive high-pressure noncompliant balloon valvuloplasty. This modification simplifies the procedural workflow and may reduce mechanical trauma to the valve apparatus.

Consistent with previous reports, we observed significant acute hemodynamic improvement with meaningful reductions in TMG without clinically relevant increases in MR. Nevertheless, the final gradient remained within the range compatible with significant stenosis, which might be expected in DMS associated with extensive MAC. Unlike rheumatic disease, in which commissural fusion can be effectively relieved by balloon commissurotomy, the obstructive substrate in DMS frequently involves circumferential annular calcification and basal leaflet rigidity, creating a relatively fixed inflow tunnel.

The mechanism underlying the observed reduction in gradient is likely multifactorial. Intravascular lithotripsy generates acoustic pressure waves that selectively induce microfractures in calcified structures while sparing surrounding soft tissue. In a study of cadaveric hearts, micro-CT demonstrated these microfractures,16 which may reduce radial stiffness of the annulus and basal leaflet segments, improve leaflet excursion, and increase effective orifice area modestly. However, because the calcified structures are not removed and the anatomical obstruction is often extensive, complete normalization of TMG is unlikely.

In this context, the primary therapeutic goal of lithotripsy-mediated calcium modification is not necessarily to completely normalize TMG, but rather to achieve a meaningful reduction in the gradient, improvement in LAP, and/or relief of symptoms, while minimizing the risk of severe MR or major procedural complications. Accordingly, once we achieved satisfactory hemodynamic improvement in our series, we avoided high-pressure balloon dilation, which may have reduced the risk of structural leaflet injury.

Compared to previous reports, we used relatively large-diameter lithotripsy balloons, which may improve circumferential contact with the calcified annulus and basal leaflet segments. This enhances energy delivery and effectiveness while allowing for controlled expansion. This may represent an additional factor contributing to the reduction of the gradient without worsening regurgitation.

From a technical standpoint, several procedural simplifications are worth noting. The entire intervention was performed using a single transseptal puncture to accommodate two steerable sheaths, eliminating the need for a septostomy. Rapid ventricular pacing during balloon inflation was not necessary, which simplified the procedure and reduced its complexity. Additionally, using ICE instead of transesophageal guidance provided precise imaging support while avoiding general anesthesia and endotracheal intubation, which is especially beneficial for elderly and high-risk patients.

Beyond the inherent limitations of the very small sample size and the single-center design, which restrict generalizability, several important knowledge gaps remain. Although lithotripsy-assisted balloon valvuloplasty leads to significant immediate hemodynamic improvement without the need for standard balloon post-dilatation, it remains uncertain whether this benefit can be consistently maintained during short- and long-term follow-up, or if routine or selective post-dilatation with conventional balloons will be necessary to optimize durability. Optimal balloon sizing remains poorly defined, and there are no standardized criteria for selecting the most appropriate dimensions based on individual valve anatomy. Additionally, potential conduction disturbances are an important area of interest. Although only transient pacing requirements were observed in our series, the long-term impact of lithotripsy-assisted balloon valvuloplasty on conduction abnormalities remains unknown. The role of cerebral embolic protection devices also deserves further investigation, as the theoretical risk of embolization caused by calcium fragmentation has not yet been systematically studied.

Future research should prioritize larger prospective studies that use standardized procedural protocols, include systematic multimodal imaging follow-up, and provide extended clinical surveillance. Such investigations are essential to better define the safety profile of lithotripsy-assisted balloon valvuloplasty, optimize procedural strategies, evaluate the durability of hemodynamic improvements, and clarify the overall clinical impact of this emerging technique.

This initial case series demonstrates that lithotripsy-assisted balloon valvuloplasty, using a dual deflectable sheath and dual-balloon strategy, is feasible and procedurally safe in selected inoperable patients with DMS. The technique consistently improved acute hemodynamics without increasing MR or causing major procedural complications, all while avoiding high-pressure balloon dilation and general anesthesia. Although this study is hypothesis-generating due to its small sample size and exploratory nature, the findings suggest that lithotripsy-assisted balloon valvuloplasty may be a promising adjunctive option for anatomically complex patients who lack conventional therapeutic alternatives. These results warrant further evaluation in larger prospective studies.

Conception and design of the research: João Silva Marques. Acquisition of data: Daniel Inácio Cazeiro, Diogo Ferreira, Fábio Viveiros, João Silva Marques. Analysis and interpretation of the data: Daniel Inácio Cazeiro, João Silva Marques. Writing of the manuscript: Daniel Inácio Cazeiro, Diogo Ferreira, Fábio Viveiros, João Silva Marques. Critical revision of the manuscript for content: Daniel Inácio Cazeiro, Diogo Ferreira, Fábio Viveiros, Catarina Oliveira, Tiago Rodrigues, Ana Rita Francisco, Cláudia Moreira Jorge, Pedro Cardoso, Fausto J. Pinto, João Silva Marques.

Written informed consent was obtained prior to all the procedures, as well as authorization for use of data for investigation purposes, according to a general clinical protocol validated by the local ethics committee.

ChatGPT 5.2 was used for linguistic correction and language refinement. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.

No authors received financial support for the research, authorship, and/or publication of this article.

The authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article.