The research team, led by Mohammed Abusharekh and Amir Abbas Mahabadi, compared the original PASCAL repair system with its second-generation iteration, the PASCAL ACE, in a cohort of 366 consecutive patients treated between 2019 and 2024. The PASCAL system, developed by Edwards Lifesciences, introduced a central spacer and independent leaflet capture as structural innovations over the earlier MitraClip platform. The ACE version refined the concept further, featuring a reduced profile, narrower paddles, and increased curvature designed to enhance leaflet approximation, improve deliverability, and distribute mechanical stress more evenly in anatomically challenging valves. Until now, however, head-to-head comparative data in real-world practice have been scarce, leaving device selection largely to operator judgment.

The Essen cohort reflected the realities of contemporary practice. Patients had a mean age of 77.7 years, and nearly 58 percent were men. All had moderate-to-severe or severe mitral regurgitation, categorized by etiology as functional, degenerative, or mixed. Crucially, the two devices were not used interchangeably. Patients receiving the ACE device were older, more frequently had atrial fibrillation, and presented with significantly more complex valve anatomy, including bileaflet or multi-scallop prolapse in 25.8 percent of cases compared with 13.1 percent in the PASCAL group. Moderate-to-severe calcification in the grasping area, leaflet clefts, and restricted leaflet mobility were also more common in the ACE cohort. In other words, clinicians were already intuitively reserving the refined device for the hardest cases.

To move beyond intuition, the investigators deployed comprehensive three-dimensional transesophageal echocardiography before and during every procedure. This imaging approach allowed precise planimetric measurement of the mitral valve orifice area, or MVOA, in late diastole at maximal leaflet opening, along with the vena contracta area, anteroposterior and mediolateral annular diameters, annular area, perimeter, and the annular sphericity index. All 3D datasets were analyzed offline by a senior echocardiographer blinded to device type and outcomes, a methodological safeguard that lends considerable weight to the findings. Procedural endpoints followed the Mitral Valve Academic Research Consortium criteria, and statistical analysis included multivariable regression and propensity score matching to address the inherent selection bias of a non-randomized comparison.

The headline result concerns the fate of the valve orifice. Before the procedure, ACE-treated patients had larger baseline orifice areas, a median of 6.55 square centimeters versus 5.87 square centimeters in the PASCAL group. After the first device was implanted, the ACE group predictably retained a larger residual orifice, 3.81 versus 3.38 square centimeters. But when the researchers calculated the relative reduction, the numbers were almost identical: a decrease of 44.5 percent with ACE versus 45.9 percent with PASCAL, a difference that did not reach statistical significance. This pattern held consistently across functional, degenerative, and mixed etiologies. In essence, both devices squeezed the valve by roughly the same proportion; the final orifice size simply mirrored what the anatomy had provided at the start.

The hemodynamic consequences followed the same logic. The transmitral mean pressure gradient, a key indicator of potential iatrogenic mitral stenosis, rose modestly in both groups, with a slightly smaller increase in the ACE cohort, from one to two millimeters of mercury difference, likely reflecting the larger residual orifice areas in that group. This detail matters clinically, because accumulating evidence suggests that a post-procedural mean gradient of five millimeters of mercury or higher predicts worse outcomes. Whether the modest gradient advantage observed with ACE after the first device translates into long-term clinical benefit remains an open question that the study’s authors flag for future investigation.

Annular remodeling told a similar story of convergence. Both devices shifted the mitral annulus from a circular toward a more elliptical geometry, with comparable relative reductions in the anteroposterior diameter and the annular sphericity index. The slightly larger post-procedural annular dimensions in the ACE group, including a small increase in mediolateral diameter, were best explained by the larger baseline annular size rather than any device-specific geometric effect. Notably, no differences in annular sphericity or transmitral gradients emerged across any of the etiological subgroups, reinforcing the conclusion that the two devices exert fundamentally similar geometric influences on the valve apparatus.

One area where the devices diverged was the need for a second implant. ACE-treated patients more often required two devices, 35.9 versus 23.5 percent, and had a larger residual vena contracta area after the first implant, particularly in degenerative regurgitation where multi-scallop prolapse and bileaflet involvement predominated. Yet after the second device, final vena contracta values and percent reductions were comparable between groups, supporting multi-device strategies as a reliable path to procedural optimization regardless of starting anatomy. Procedural success was uniformly excellent, 100 percent with ACE and 99.6 percent with PASCAL, with no cases of single leaflet device attachment, leaflet injury, or chordal entrapment in either cohort.

The study also documented a clear temporal shift in practice. In the early years, the original PASCAL device accounted for the majority of procedures, but after ACE was introduced at the center in August 2020, its utilization climbed steadily and eventually became the dominant choice. This evolution parallels a rising proportion of patients presenting with complex valve morphology and mixed etiologies, suggesting that the refined device arrived just as the treated population was becoming more challenging. A sensitivity analysis comparing the first fifty PASCAL cases with later ones showed that operator experience improved acute efficacy without compromising safety, partially addressing concerns about a learning curve.

Perhaps the most consequential finding came from the multivariable analysis. After adjusting for age, atrial fibrillation, ejection fraction, etiology, anatomical complexity, baseline dimensions, and temporal trends, the differences in post-procedural orifice and vena contracta areas that appeared in the crude comparison vanished entirely. Device type was not an independent predictor of any geometric or hemodynamic outcome. A stratified analysis by baseline valve size added nuance: device-specific effects on narrowing only emerged in mid-sized valves, where ACE proved more area-sparing in the four-to-five square centimeter range, while at the extremes the underlying leaflet anatomy reigned supreme. The authors’ conclusion is unambiguous: baseline valve anatomy, rather than device selection, is the predominant determinant of post-procedural geometry and hemodynamics. For the growing number of heart teams weighing PASCAL against PASCAL ACE, the message is to choose based on the valve in front of them, favoring the ACE’s narrower paddles for complex, restricted, or calcified anatomies and the original PASCAL’s broader coaptation zone where wide leaflet grasping is needed, always guided by meticulous three-dimensional imaging rather than by any assumption that one device is inherently superior.

Subject of Research: Three-dimensional mitral valve geometry and outcomes after transcatheter edge-to-edge repair comparing PASCAL and PASCAL ACE devices

Article Title: Three-dimensional mitral valve geometry after transcatheter edge-to-edge repair: PASCAL versus PASCAL-ACE—implications for devices selection

Article References: Abusharekh, M., Kampf, J., Schindhelm, F., Jürgens, F., Dykun, I., Al-Rashid, F., Totzeck, M., Rassaf, T., & Mahabadi, A. A. (2026). Three-dimensional mitral valve geometry after transcatheter edge-to-edge repair: PASCAL versus PASCAL-ACE—implications for devices selection. Clinical Research in Cardiology. https://doi.org/10.1007/s00392-026-03031-0

Image Credits: AI Generated

DOI: 10.1007/s00392-026-03031-0

Keywords: mitral regurgitation, transcatheter edge-to-edge repair, PASCAL, PASCAL ACE, 3D echocardiography, mitral valve orifice area, annular remodeling, interventional cardiology, degenerative mitral regurgitation, functional mitral regurgitation, device selection, heart team

The study, part of the ongoing Regensburg Trial on TMVR Techniques in Mitral Regurgitation (RETORT-MR), enrolled 311 patients with severe mitral regurgitation between December 2017 and March 2024. All were considered clinically well compensated before their procedure, meaning they showed no obvious signs of hypervolemia or congestion on physical examination. The researchers calculated each patient’s estimated plasma volume status, or ePVS, a surrogate marker that quantifies the proportional deviation of actual plasma volume from the ideal value. The calculation relies on Hakim’s formula, which derives actual plasma volume from the hematocrit and body weight using sex-dependent constants, and compares it against ideal plasma volume estimates established by Longo and colleagues. Because it requires nothing more than a complete blood count and a scale, the ePVS can be computed in any clinic within minutes, at essentially no cost.

The median ePVS in the cohort was -3.8 percent, with an interquartile range spanning -10.3 to +3.6 percent, indicating that most patients carried slightly less plasma volume than the theoretical ideal. Using receiver operating characteristic analysis anchored to one-year mortality, the investigators identified an optimal cut-off of +0.36 percent for ePVS and 2794 pg/mL for NT-proBNP, the established blood biomarker of myocardial wall stress. Fifty-one patients died during a median follow-up of twelve months, with a median time to death of 422 days. When the cohort was split at these thresholds, the differences in survival were stark and statistically unmistakable.

Patients whose preprocedural ePVS exceeded the cut-off had a Kaplan-Meier estimated mortality of 14.4 percent at one year, compared with just 4.7 percent among those below the threshold. By five years, the gap had widened dramatically: 63.0 percent of patients with elevated ePVS had died, versus 26.0 percent of those with lower values, a difference the log-rank test flagged as highly significant. Elevated NT-proBNP told a similar story, with one-year mortality of 14.6 percent versus 3.5 percent. Crucially, both markers survived multivariable adjustment for competing risk factors. Elevated ePVS carried a hazard ratio of 2.38 for all-cause mortality, while elevated NT-proBNP carried a hazard ratio of 4.30, confirming that each independently predicted death after the procedure.

Perhaps the most striking finding emerged when the two biomarkers were combined into a single trichotomous congestion variable. Patients with both markers above their cut-offs faced a hazard ratio of 14.27 for mortality compared with those in whom neither was elevated, a nearly fifteen-fold increase in risk. Even one elevated marker alone conferred a hazard ratio of 6.67. Kaplan-Meier curves for the three groups separated in a clean, stepwise fashion, with one-year mortality climbing from 1.9 percent in the double-negative group to 8.2 percent with one marker elevated and 21.5 percent with both. Five-year mortality followed the same gradient, reaching 64.8 percent in the doubly elevated group. The authors argue this reflects the integration of two fundamentally different congestion phenotypes into one comprehensive risk picture.

That pathophysiological distinction is central to the study’s significance. NT-proBNP is released by cardiac muscle cells in response to end-diastolic wall stress caused by pressure or volume overload inside the heart, and it is tightly linked to cardiac function. In this cohort, patients with elevated NT-proBNP indeed showed the expected signature of advanced myocardial disease: a higher prevalence of heart failure with reduced ejection fraction, lower left ventricular ejection fractions, reduced tricuspid annular plane systolic excursion, and more frequent secondary mitral regurgitation. Elevated ePVS, by contrast, was not associated with impaired systolic function. Instead, it marked a composite phenotype dominated by intravascular volume expansion, hemodilution, renal dysfunction, and systemic congestion. Patients with high ePVS were slightly older, had significantly lower estimated glomerular filtration rates, lower body mass index, lower hemoglobin and hematocrit, and required higher doses of loop diuretics.

A critical methodological question was whether ePVS simply repackages anemia, which is itself a known predictor of poor outcomes in heart failure. Because hematocrit is a direct component of the ePVS formula, the researchers built nested multivariable Cox models comparing ePVS against hematocrit, both as a continuous variable and as a sex-specific dichotomized variable. The results were decisive: hematocrit alone was not independently associated with mortality and did not improve model fit, whereas ePVS remained significant even when hematocrit was included, and adding ePVS significantly improved model fit in likelihood-ratio tests. Time-dependent reclassification analyses using integrated discrimination improvement showed that ePVS added significant prognostic information at a two-year horizon. This suggests the prognostic power lies not in anemia itself but in the multifactorial processes of plasma volume expansion and pseudoanemia that ePVS captures.

The findings held across both major etiologies of mitral regurgitation. In patients with primary, or degenerative, mitral regurgitation, elevated ePVS carried a univariable hazard ratio of 6.26, while in those with secondary or mixed disease the hazard ratio was 2.95, both statistically significant. The combined ePVS and NT-proBNP variable also stratified mortality in both subgroups. Regarding cardiovascular death specifically, of the 51 total deaths, 26 were cardiovascular in origin, and elevated ePVS maintained its independent association with cardiovascular mortality in multivariable models, with a hazard ratio of 2.66. Interestingly, only NT-proBNP, not ePVS alone, predicted rehospitalization for heart failure, which the authors interpret as evidence that ePVS marks a subtler, subclinical form of congestion that drives progressive organ dysfunction and death rather than acute decompensation requiring readmission.

The clinical implications are considerable. M-TEER candidates are a heterogeneous, high-risk population in whom traditional risk assessment has struggled to identify who will benefit most and who will deteriorate despite a technically successful procedure. The study found that, alongside the biomarkers, only a reduced left ventricular ejection fraction, severe preprocedural tricuspid regurgitation, and severe residual mitral regurgitation after the procedure remained independently associated with mortality, underscoring that optimal heart failure therapy and excellent procedural results remain essential. But the ePVS offers something those measures do not: a zero-cost, universally available window into subclinical intravascular congestion in patients who appear clinically dry. The authors caution that the estimated plasma volume depends on multiple variables and provides only limited information about true quantitative plasma volume, so it should not dictate therapy on its own.

Limitations temper the enthusiasm appropriately. RETORT-MR is a single-center study with a relatively small cohort, a low absolute number of deaths, and a substantial proportion of patients lost to follow-up, all of which constrain statistical power, particularly for the reclassification analyses and cause-specific mortality. The authors themselves emphasize that the results warrant validation in larger cohorts with more adverse events. Nevertheless, the consistency of the signal across etiologies, its independence from hematocrit and established covariates, and the sheer magnitude of the combined-marker hazard ratio make a compelling case. If confirmed, a calculation performable from a routine blood draw could become a standard element of preprocedural evaluation, flagging the silent fluid overload that today’s stethoscopes cannot hear and tomorrow’s outcomes depend on.

Subject of Research: Prognostic value of estimated plasma volume status in patients undergoing transcatheter edge-to-edge mitral valve repair

Article Title: The estimated plasma volume status is an independent predictor for mortality in patients undergoing transcatheter mitral valve repair

Article References: The estimated plasma volume status is an independent predictor for mortality in patients undergoing transcatheter mitral valve repair. (n.d.). https://doi.org/10.1007/s00392-026-03021-2

Image Credits: AI Generated

DOI: 10.1007/s00392-026-03021-2

Keywords: M-TEER, mitral regurgitation, ePVS, NT-proBNP, congestion, heart failure, plasma volume status, mortality prediction, biomarkers, transcatheter valve repair, risk stratification, cardiology