Muralidhar Padala

Objectives: Functional mitral regurgitation (FMR) remains challenging to repair surgically, as highlighted by the Cardiothoracic Surgical Trials Network (CTSN) trial, which showed limited durability of mitral annuloplasty. We previously demonstrated in vivo and experimentally that papillary muscle approximation (PMA) can improve mitral valve (MV) function, with or without annuloplasty. In this study, we assessed valve biomechanics after PMA, mitral annuloplasty, and their combination in imaging-derived computational models. Methods: 3D echo images were obtained in three pigs with heart failure, dilated ventricles, and FMR. Each echo dataset was segmented, and a subject-specific computational model of the MV was created. Virtual FMR repair was performed on each valve using PMA, annuloplasty with true-sized (40 mm) and downsized (38 mm and 36 mm) rings, and a combination of both techniques. For each repair strategy, leaflet closure was simulated, and MV geometry and biomechanics at peak systole were evaluated. Results: Isolated PMA improved valve coaptation, reduced leaflet stresses and chordal tension forces, but failed to completely eliminate FMR. Isolated mitral annuloplasty also improved coaptation, but overall provided only limited geometric and biomechanical benefits. Combining annuloplasty and PMA resulted in the most favorable outcomes, eliminating FMR, increasing coaptation length (up to 97.7%), and reducing leaflet stresses (up to 43.7%) and chordal forces (up to 43.0%). Conclusions: While both PMA and annuloplasty independently improved MV function, neither technique fully resolved FMR on its own. Their combination yielded the most favorable repair outcomes, eliminating FMR and significantly improving valve geometry and biomechanics without the need for excessive annular downsizing.

Hypovolemic shock is one of the leading causes of death in the military. The current methods of assessing hypovolemia in field settings rely on a clinician assessment of vital signs, which is an unreliable assessment of hypovolemia severity. These methods often detect hypovolemia when interventional methods are ineffective. Therefore, there is a need to develop real-time sensing methods for the early detection of hypovolemia. Previously, our group developed a random-forest model that successfully estimated absolute blood-volume status (ABVS) from noninvasive wearable sensor data for a porcine model (n = 6). However, this model required normalizing ABVS data using individual baseline data, which may not be present in crisis situations where a wearable sensor might be placed on a patient by the attending clinician. We address this barrier by examining seven individual baseline-free normalization techniques. Using a feature-specific global mean from the ABVS and an external dataset for normalization demonstrated similar performance metrics compared to no normalization (normalization: R² = 0.82 ± 0.025|0.80 ± 0.032, AUC = 0.86 ± 5.5 × 10⁻³|0.86 ± 0.013, RMSE = 28.30 ± 0.63%|27.68 ± 0.80%; no normalization: R² = 0.81 ± 0.045, AUC = 0.86 ± 8.9 × 10⁻³, RMSE = 28.89 ± 0.84%). This demonstrates that normalization may not be required and develops a foundation for individual baseline-free ABVS prediction.

Several interventional therapies are in development to treat functional tricuspid regurgitation. Most have failed to achieve adequate efficacy, as animal models of this lesion are lacking. We developed a new image-guided technique in swine, by tethering the tricuspid valve chordae using echo-guided chordal encircling snares. Five swine underwent baseline echocardiographic assessment of tricuspid valve function, followed by echo-guided placement of snares that encircle the chordae inserting into the anterior and posterior tricuspid valve leaflets. Tethering these snares and stabilizing them on the right ventricle caused the regurgitant fraction to increase from 8.48±5.38% to 48.76±12.5%, and the valve tenting area to increase from 60.26±52.19 to 160.9±86.92 mm². Image-guided chordal encircling snares could reproducibly induce clinically significant levels of functional tricuspid regurgitation and create a valve geometry like that seen in patients, providing a new animal model for use to study novel interventional devices. Graphical Abstract

Surgical repair of functional mitral regurgitation (FMR) that occurs in nearly 60% of heart failure (HF) patients is currently performed with undersizing mitral annuloplasty (UMA), which lacks short- and long-term durability. Heterogeneity in valve geometry makes tailoring this repair to each patient challenging, and predictive models that can help with planning this surgery are lacking. In this study, we present a 3D echo-derived computational model, to enable subject-specific, pre-surgical planning of the repair. Three computational models of the mitral valve were created from 3D echo data obtained in three pigs with HF and FMR. An annuloplasty ring model in seven sizes was created, each ring was deployed, and post-repair valve closure was simulated. The results indicate that large annuloplasty rings (> 32 mm) were not effective in eliminating regurgitant gaps nor in restoring leaflet coaptation or reducing leaflet stresses and chordal tension. Smaller rings (≤ 32 mm) restored better systolic valve closure in all investigated cases,but excessive valve tethering and restricted motion of the leaflets were still present. This computational study demonstrates that for effective correction of FMR, the extent of annular reduction differs between subjects, and overly reducing the annulus has deleterious effects on the valve.