Leaflet remodeling reduces tricuspid valve function in a computational model.

Tricuspid valve leaflets have historically been considered "passive flaps". However, we have recently shown that tricuspid leaflets actively remodel in sheep with functional tricuspid regurgitation. We hypothesize that these remodeling-induced changes reduce leaflet coaptation and, therefore, contribute to valvular dysfunction. To test this, we simulated the impact of remodeling-induced changes on valve mechanics in a reverse-engineered computer model of the human tricuspid valve. To this end, we combined right-heart pressures and tricuspid annular dynamics recorded in an ex vivo beating heart, with subject-matched in vitro measurements of valve geometry and material properties, to build a subject-specific finite element model. Next, we modified the annular geometry and boundary conditions to mimic changes seen in patients with pulmonary hypertension. In this model, we then increased leaflet thickness and stiffness and reduced the stretch at which leaflets stiffen, which we call "transition-λ." Subsequently, we quantified mean leaflet stresses, leaflet systolic angles, and coaptation area as measures of valve function. We found that leaflet stresses, leaflet systolic angle, and coaptation area are sensitive to independent changes in stiffness, thickness, and transition-λ. When combining thickening, stiffening, and changes in transition-λ, we found that anterior and posterior leaflet stresses decreased by 26% and 28%, respectively. Furthermore, systolic angles increased by 43%, and coaptation area decreased by 66%; thereby impeding valve function. While only a computational study, we provide the first evidence that remodeling-induced leaflet thickening and stiffening may contribute to valvular dysfunction. Targeted suppression of such changes in diseased valves could restore normal valve mechanics and promote leaflet coaptation.

Impact of tricuspid annuloplasty device shape and size on valve mechanics-a computational study.

Background: Tricuspid valve disease significantly affects 1.6 million Americans. The gold standard treatment for tricuspid disease is the implantation of annuloplasty devices. These ring-like devices come in various shapes and sizes. Choices for both shape and size are most often made by surgical intuition rather than scientific rationale. Methods: To understand the impact of shape and size on valve mechanics and to provide a rational basis for their selection, we used a subject-specific finite element model to conduct a virtual case study. That is, we implanted 4 different annuloplasty devices of 6 different sizes in our virtual patient. After each virtual surgery, we computed the coaptation area, leaflet end-systolic angles, leaflet stress, and chordal forces. Results: We found that contoured devices are better at normalizing end-systolic angles, whereas the one flat device, the Edwards Classic, maximized the coaptation area and minimized leaflet stress and chordal forces. We further found that reducing device size led to increased coaptation area but also negatively impacted end-systolic angles, stress, and chordal forces. Conclusions: Based on our analyses of the coaptation area, leaflet motion, leaflet stress, and chordal forces, we found that device shape and size have a significant impact on valve mechanics. Thereby, our study also demonstrates the value of simulation tools and device tests in "virtual patients." Expanding our study to many more valves may, in the future, allow for universal recommendations.

Geometric data of commercially available tricuspid valve annuloplasty devices.

Tricuspid valve annuloplasty is the gold standard surgical treatment for functional tricuspid valve regurgitation. During this procedure, ring-like devices are implanted to reshape the diseased tricuspid valve annulus and to restore function. For the procedure, surgeons can choose from multiple available device options varying in shape and size. In this article, we provide the three-dimensional (3D) scanned geometry (*.stl) and reduced midline (*.vtk) of five different annuloplasty devices of all commercially available sizes. Three-dimensional images were captured using a 3D scanner. After extracting the surface geometry from these images, the images were converted to 3D point clouds and skeletonized to generate a 3D midline of each device. In total, we provide 30 data sets comprising the Edwards Classic, Edwards MC3, Edwards Physio, Medtronic TriAd, and Medtronic Contour 3D of sizes 26-36. This dataset can be used in computational models of tricuspid valve annuloplasty repair to inform accurate repair geometry and boundary conditions. Additionally, others can use these data to compare and inspire new device shapes and sizes.

Untangling the mechanisms of pulmonary arterial hypertension-induced right ventricular stiffening in a large animal model.

Pulmonary hypertension (PHT) is a devastating disease with low survival rates. In PHT, chronic pressure overload leads to right ventricle (RV) stiffening; thus, impeding diastolic filling. Multiple mechanisms may contribute to RV stiffening, including wall thickening, microstructural disorganization, and myocardial stiffening. The relative importance of each mechanism is unclear. Our objective is to use a large animal model to untangle these mechanisms. Thus, we induced pulmonary arterial hypertension (PAH) in sheep via pulmonary artery banding. After eight weeks, the hearts underwent anatomic and diffusion tensor MRI to characterize wall thickening and microstructural disorganization. Additionally, myocardial samples underwent histological and gene expression analyses to quantify compositional changes and mechanical testing to quantify myocardial stiffening. Finally, we used finite element modeling to disentangle the relative importance of each stiffening mechanism. We found that the RVs of PAH animals thickened most at the base and the free wall and that PAH induced excessive collagen synthesis, increased cardiomyocyte cross-sectional area, and led to microstructural disorganization, consistent with increased expression of fibrotic genes. We also found that the myocardium itself stiffened significantly. Importantly, myocardial stiffening correlated significantly with collagen synthesis. Finally, our computational models predicted that myocardial stiffness contributes to RV stiffening significantly more than other mechanisms. Thus, myocardial stiffening may be the most important predictor for PAH progression. Given the correlation between myocardial stiffness and collagen synthesis, collagen-sensitive imaging modalities may be useful for estimating myocardial stiffness and predicting PAH outcomes. STATEMENT OF SIGNIFICANCE: Ventricular stiffening is a significant contributor to pulmonary hypertension-induced right heart failure. However, the mechanisms that lead to ventricular stiffening are not fully understood. The novelty of our work lies in answering this question through the use of a large animal model in combination with spatially- and directionally sensitive experimental techniques. We find that myocardial stiffness is the primary mechanism that leads to ventricular stiffening. Clinically, this knowledge may be used to improve diagnostic, prognostic, and therapeutic strategies for patients with pulmonary hypertension.

Comparison of Repair vs Replacement in Calcific and Rheumatic Mitral Disease.

BACKGROUND: The benefit of repair over replacement of rheumatic or calcified mitral valve (MV) is debatable. METHODS: Patients who underwent MV repair or replacement for rheumatic or calcified MV disease between 2006 and 2020 were identified in the Polish National Registry of Cardiac Surgery Procedures. Patients who underwent additional procedures other than coronary artery bypass grafting or tricuspid valve surgery, as well as redo or emergency cases, were excluded. The long-term survival was verified based on National Health Fund registry data. The survival was compared between MV repair and replacement in the whole cohort and after propensity score matching. RESULTS: We included 4338 patients: 1859 (43%) with pure mitral regurgitation and 2479 (57%) with mitral stenosis. MV was repaired in 543 patients (29%) with pure regurgitation and 126 (5.1%) with stenosis (P < .001). In total, 984 (23%) patients underwent concomitant coronary artery bypass grafting and 1358 (32%) tricuspid valve surgery. MV repair improved survival (hazard ratio 0.81; 95% CI 0.68-0.97; P = .022) in patients with no mitral stenosis, and had no effect in mitral stenosis (hazard ratio 1.17; 95% CI 0.85-1.59; P = .332). The results were confirmed in propensity-matched cohorts. The freedom from MV reoperation at 10 years was 95.5% ± 1.2% after repair and 96.0% ± 0.7% after MV replacement (P = .416) in the absence of stenosis and 91.8% ± 3.4% after repair vs 95.9% ± 0.5% after replacement in patients with mitral stenosis (P = .065). CONCLUSIONS: Repair of rheumatic/calcified mitral valve should be a preferred option in patients with no mitral stenosis, but confers no benefit if mitral stenosis is present.

Untangling the mechanisms of pulmonary hypertension-induced right ventricular stiffening in a large animal model.

Background: Pulmonary arterial hypertension (PHT) is a devastating disease with low survival rates. In PHT, chronic pressure overload leads to right ventricle (RV) remodeling and stiffening; thus, impeding diastolic filling and ventricular function. Multiple mechanisms contribute to RV stiffening, including wall thickening, microstructural disorganization, and myocardial stiffening. The relative importance of each mechanism is unclear. Our objective is to use a large animal model as well as imaging, experimental, and computational approaches to untangle these mechanisms. Methods: We induced PHT in eight sheep via pulmonary artery banding. After eight weeks, the hearts underwent anatomic and diffusion tensor MRI to characterize wall thickening and microstructural disorganization. Additionally, myocardial samples underwent histological and gene expression analyses to quantify compositional changes and mechanical testing to quantify myocardial stiffening. All findings were compared to 12 control animals. Finally, we used computational modeling to disentangle the relative importance of each stiffening mechanism. Results: First, we found that the RVs of PHT animals thickened most at the base and the free wall. Additionally, we found that PHT induced excessive collagen synthesis and microstructural disorganization, consistent with increased expression of fibrotic genes. We also found that the myocardium itself stiffened significantly. Importantly, myocardial stiffening correlated significantly with excess collagen synthesis. Finally, our model of normalized RV pressure-volume relationships predicted that myocardial stiffness contributes to RV stiffening significantly more than other mechanisms. Conclusions: In summary, we found that PHT induces wall thickening, microstructural disorganization, and myocardial stiffening. These remodeling mechanisms were both spatially and directionally dependent. Using modeling, we show that myocardial stiffness is the primary contributor to RV stiffening. Thus, myocardial stiffening may be an important predictor for PHT progression. Given the significant correlation between myocardial stiffness and collagen synthesis, collagen-sensitive imaging modalities may be useful for non-invasively estimating myocardial stiffness and predicting PHT outcomes.

Results of aortic valve replacement for aortic stenosis and moderate functional mitral regurgitation.

BACKGROUND: Referral and admission echocardiography (ECHO) in patients scheduled for aortic valve replacement (AVR) with aortic stenosis (AS) may differ in the assessment of moderate functional mitral regurgitation (FMR). AIMS: Our study was to determine the truly moderate-FMR and evaluate its impact on survival. METHODS: We conducted an observational study of patients referred for AVR with AS and up to moderate FMR, between 2014 and 2019. Patients were divided into three groups: (1) no/mild (N-FMR); (2) moderate-FMR on one ECHO (either at referral or admission) termed incidental (I-FMR); (3) moderate FMR in two studies (both at referral and admission) termed permanent (PM-FMR). RESULTS: The referral and admission assessment were performed median 35 days apart. Of the 679 elective patients who underwent elective isolated AVR, 516 patients had N-FMR, 102 patients had I-FMR, and 61 patients had PM-FMR. Median follow-up was 46 months (22.5-58.5); max 73.3. 30-day mortality was 2.5% vs. 1% vs. 8.2% (N-FMR vs. I-FMR vs. PM-FMR, respectively; P = 0.01). Five-year survival was 84.1% in N-FMR vs. 88.5% in I-FMR vs. 60.6% in PM-FMR group, where was the lowest (P <0.001). In multivariable modeling PM-FMR increased mortality (hazard ratio [HR], 1.88 [1.05-3.37]; P = 0.03). The I-FMR had no effect on mortality (HR, 0.67 [0.32-1.37]; P = 0.28). Five-year survival after excluding 30-day mortality was 86.3% vs. 89.4% vs. 66.0%; (N-FMR vs. I-FMR vs. PM-FMR, respectively; P = 0.02). The PM-FMR increased late mortality (HR, 2.17 [1.14-4.15]; P = 0.01). CONCLUSIONS: In patients undergoing isolated AVR for AS, the presence of permanent moderate FMR significantly impacts 30-day and mid-term survival.

Myocardial protection using single dose del Nido Cardioplegia with and without topical cooling.

INTRODUCTION: Del Nido cardioplegia (DN) is gaining acceptance in adult cardiac surgery but there is paucity of experimental data regarding its efficacy. We set out to assess the safety and efficacy of single-dose DN with and without topical cooling (TC) versus multi-dose blood cardioplegia (BC). METHODS: Thirty-two healthy adult sheep had pressure-volume (PV) catheters placed in the left (LV) and right (RV) ventricle. Animals were assigned to receive cold (4°C) antegrade solution for a 60-min arrest using: (1) multi-dose (every 20 min) BC with TC (n = 11), (2) single-dose DN with TC (DN-C, n = 10), or (3) single-dose DN without TC (DN-H, n = 11). LV and RV PV-derived indexes, epicardial echocardiographic strains, and blood samples were acquired before CPB and at 1, 2, and 3 h of reperfusion. Dobutamine bolus (2.5 µg) was given after 3 h to test for myocardial reserve. RESULTS: Time to rhythm restoration was shortest (54 ± 29 s, 118 ± 167 s, and 172 ± 170 s for DN-H, DN-C, and BC, respectively; p = 0.024) and number of shocks lowest (1.7 ± 1.8, 3.6 ± 2.8, and 5.6 ± 4.6 for DN-H, DN-C, and BC, respectively; p = 0.020) in DN-H group. Hemodynamic, load-independent myocardial function, echocardiographic, and metabolic data revealed only slight differences between groups. Troponin I levels did not differ between groups. With dobutamine, preload-recruitable stroke work of both LV (136 ± 50%, 131 ± 31%, 142 ± 58% for BC, DN-C and DN-H, respectively; p = 0.993) and RV (161 ± 67%, 185 ± 45%, 166 ± 75% for BC, DN-C and DN-H respectively; p = 0.580) increased similarly. CONCLUSIONS: Single-dose DN cardioplegia with or without topical cooling offered comparable biventricular myocardial protection to multi-dose BC for a 60-min arrest in sheep.

The impact of thickness heterogeneity on soft tissue biomechanics: a novel measurement technique and a demonstration on heart valve tissue.

The mechanical properties of soft tissues are driven by their complex, heterogeneous composition and structure. Interestingly, studies of soft tissue biomechanics often ignore spatial heterogeneity. In our work, we are therefore interested in exploring the impact of tissue heterogeneity on the mechanical properties of soft tissues. Therein, we specifically focus on soft tissue heterogeneity arising from spatially varying thickness. To this end, our first goal is to develop a non-destructive measurement technique that has a high spatial resolution, provides continuous thickness maps, and is fast. Our secondary goal is to demonstrate that including spatial variation in thickness is important to the accuracy of biomechanical analyses. To this end, we use mitral valve leaflet tissue as our model system. To attain our first goal, we identify a soft tissue-specific contrast protocol that enables thickness measurements using a Keyence profilometer. We also show that this protocol does not affect our tissues' mechanical properties. To attain our second goal, we conduct virtual biaxial, bending, and buckling tests on our model tissue both ignoring and considering spatial variation in thickness. Thereby, we show that the assumption of average, homogeneous thickness distributions significantly alters the results of biomechanical analyses when compared to including true, spatially varying thickness distributions. In conclusion, our work provides a novel measurement technique that can capture continuous thickness maps non-invasively, at high resolution, and in a short time. Our work also demonstrates the importance of including heterogeneous thickness in biomechanical analyses of soft tissues.

Surgical and transcatheter aortic valve replacement for severe aortic stenosis in low-risk elective patients: Analysis of the Aortic Valve Replacement in Elective Patients From the Aortic Valve Multicenter Registry.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) remains the preferred strategy for high-risk or elderly individuals with aortic valve (AV) stenosis who are not considered to be optimal surgical candidates. Recent evidence suggests that low-risk patients may benefit from TAVI as well. The current study evaluates midterm survival in low-risk patients undergoing elective surgical AV replacement (SAVR) versus TAVI. METHODS: The Aortic Valve Replacement in Elective Patients From the Aortic Valve Multicenter Registry (AVALON) compared isolated elective transfemoral TAVI or SAVR with sternotomy or minimally invasive approach in low-risk individuals performed between 2015 and 2019. Propensity score matching was conducted to determine SAVR controls for TAVI group in a 1-to-3 ratio with 0.2 caliper. RESULTS: A total of 2393 patients undergoing elective surgery (1765 SAVR and 629 TAVI) with median European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) score 1.81 (interquartile range [IQR], 1.36 to 2.53]) were initially included. Median follow-up was 2.72 years (IQR, 1.32-4.08; max 6.0). Propensity score matching returned 329 TAVI cases and 593 SAVR controls. Thirty-day mortality was 11 out of 329 (3.32%) in TAVI and 18 out of 593 (3.03%) in SAVR (risk ratio, 1.10; 95% CI, 0.52-2.37; P = .801) groups, respectively. At 2 years, survival curves began to diverge in favor of SAVR, which was associated with 30% lower mortality (hazard ratio, 0.70; 95% CI, 0.496-0.997; P = .048). CONCLUSIONS: Our data did not demonstrate a survival difference between TAVI and SAVR during the first 2 postprocedure years. After that time, SAVR is associated with improved survival. Extended observations from randomized trials in low-risk patients undergoing elective surgery are warranted to confirm these findings and draw definitive conclusions.

Impact of reductive tricuspid ring annuloplasty on right ventricular size, geometry and strain in an ovine model of functional tricuspid regurgitation.

OBJECTIVES: Reductive ring annuloplasty of the tricuspid annulus represents the contemporary surgical approach to functional tricuspid regurgitation (FTR). We set out to investigate the influence of moderate reductive tricuspid ring annuloplasty on tricuspid regurgitation and right ventricular (RV) size, geometry and strain in an ovine model of chronic FTR. METHODS: Eight healthy Dorsett male sheep (62.8 + 2kg) underwent a left thoracotomy for placement and tightening of pulmonary artery band to at least double proximal pulmonary artery blood pressure. After 8 weeks of recovery, animals underwent sternotomy, epicardial echocardiography and sonomicrometry crystal implantation. Six crystals were placed around tricuspid annulus and 13 on RV free wall epicardium along 3 parallels defining 3 wall regions (basal, mid and lower) and 1 on the RV apex. All animals underwent beating heart implantation of 26 mm MC3 annuloplasty ring during a second cardiopulmonary bypass run after baseline data acquisition. Simultaneous haemodynamic, sonomicrometry and echocardiography data were acquired at Baseline and after reductive tricuspid ring annuloplasty. RESULTS: Implantation of reductive ring annuloplasty resulted in 47 ± 7% annular area reduction (996 ± 152 mm vs 516 ± 52 mm2, P = 0.0002) and significantly decreased RV end-diastolic volume (185 ± 27 vs 165 ± 30 ml, P = 0.02). Tricuspid ring annuloplasty effectively reduced FTR grade (3.75 ± 0.6 vs 0.3 ± 0.5, P = 0.00004) and had little influence on RV function, cross-sectional area, radius of curvature or free wall regional strains. CONCLUSIONS: In adult sheep with 8 weeks of pulmonary artery banding and FTR, tricuspid annulus reduction of 47% with prosthetic ring annuloplasty effectively abolished FTR while maintaining regional RV function and strain patterns.

Vasorelaxing properties of the perivascular tissue of the human radial artery.

OBJECTIVES: Perivascular adipose tissue (PVAT) surrounding the human internal thoracic artery exhibits anticontractile and vasorelaxing properties associated with the adipocyte-derived relaxing factor (ADRF). The goal of our study was to assess if perivascular tissue of the human radial artery (RA) also exhibits such anticontractile/vasorelaxant properties. It could be especially relevant in preventing RA spasms. METHODS: The study was performed on isolated segments of human pedicled RA. Its skeletonized fragments were suspended on stainless steel wire hooks and gradually contracted with serotonin to establish the concentration-effect relationship in the presence/absence of PVAT. Skeletonized arterial segments were precontracted with a single dose of 10-6 M serotonin (EC80). The 5-ml PVAT aliquots (from PVAT incubated in Krebs-Henseleit solution) were transferred to the RA tissue bath resulting in its relaxation. Subsequently, we investigated if ADRF is dependent on endothelial vasorelaxants (nitric oxide and prostacyclin). We attempted to find the potassium channel responsible for mediating the activity of ADRF using different potassium channel blockers. RESULTS: RA without PVAT contracted more strongly in response to serotonin compared to RA with PVAT [Emax: 108.3 (20.2) vs 76.1 (13.5) mN]. The PVAT aliquot relaxed precontracted RA rings at 43% (2.4%) [72.2 (15.6) to 41.0 (5.6) mN]. ADRF is independent of endothelial vasorelaxants; hence, the addition of NG-monomethyl-l-arginine and indomethacin did not change the vasorelaxant response. Neither of the potassium channel blockers participated in the activity of ADRF. CONCLUSIONS: PVAT of human RA exhibits anticontractile/vasorelaxant properties that are inherently associated with ADRF secretion. We confirmed the endothelial-independent mechanism of the activity of ADRF. However, we failed to find the potassium channel responsible for the action of ADRF.

Outcome comparison of different approaches to aortic root aneurysm.

BACKGROUND: The treatment of aortic root aneurysm remains challenging for both cardiac surgeons and cardiologists. AIMS: This study aimed to assess and compare the long-term outcomes of different approaches to aortic root replacement (ARR). METHODS: All elective patients operated for aortic root aneurysm with or without aortic regurgitation at our institution over a 10-year period were included. We excluded patients with any degree of aortic stenosis and with active endocarditis. We assessed mortality, freedom from reoperation, freedom from aortic valve regurgitation, and the rate of hemorrhagic and thromboembolic complications. RESULTS: Two hundred and four patients underwent elective aortic root replacement: 107 (53%) valve-sparing aortic root replacement (VSARR), 35 (17%) mechanical Bentall procedure (MB), and 62 (30%) Bio-Bentall procedure (BB). Early mortality for VSARR, BB, and MB group was 2.8%, 4.8%, and 0%, respectively (P = 0.40). Estimated 5-year survival was: 90.2% vs. 78.4% vs. 94.2%, respectively (P = 0.12), 5-year freedom from reoperation: 97.8%, 96.6%, and 96.8%, respectively (P = 0.99). Estimat-ed 5-year freedom from complications was: 94.2%, 83.1% and 57.3% in the VSARR, BB and MB group, respectively (P <0.001). On last follow-up echocardiography, 90.5%, 98.4%, and 97.1% (P = 0.08) of patients were free from aortic regurgitation grade 2 or higher. The median (IQR) aortic valve peak gradient was 9 (6-12) mm Hg, 12 (10-18) mm Hg and 16 (14-22) mm Hg, respectively (P <0.001). Complications were predicted by mechanical Bentall (hazard ratio, 6.70 [2.54-17.63]; P <0.001). CONCLUSION: With the same mortality, freedom from reoperation, and a minimal late complication rate in comparison with mechanical Bentall and Bio-Bentall, VSARR might be the preferred approach to aortic root aneurysm.

Repair or Replacement for Secondary Mitral Regurgitation: Results From Polish National Registry.

BACKGROUND: The optimal surgical strategy (repair vs replacement) for patients with secondary mitral (MV) regurgitation is questionable. METHODS: Patients who underwent MV repair or replacement for functional or ischemic mitral regurgitation between 2006 and 2017 were identified in Polish National Registry of Cardiac Surgery Procedures. Patients, who underwent additional procedures other than coronary artery bypass grafting or tricuspid valve surgery, as well as redo or emergency cases, were excluded. The long-term survival was verified based on National Health Fund registry. The survival was compared between MV repair and replacement both in the whole cohort and after propensity score matching. The Cox regression was used to seek for independent predictors of survival. RESULTS: Of 7633 identified patients, 1793 (23%) underwent MV replacement and 5840 (77%) underwent MV repair. Coronary artery bypass surgery was performed together with MV repair in 3992 (69%) patients and together with MV replacement in 915 (52%) patients (P < .001). Tricuspid valve surgery was added to 1393 (24%) MV repairs and to 561 (32%) MV replacements (P < .001). The crude actuarial 5-year survival was 71% (95% confidence interval [CI], 70%-72%) in the repair group and 66% (95% CI, 63%-68%) in the replacement group (P < .001). MV replacement was an independent predictor of mortality (hazard ratio, 1.32; 95% CI, 1.17-1.49) (P < .001) in Cox regression modeling. In the propensity-matched cohort (1105 pairs), the long-term mortality was also significantly higher in the replacement group (hazard ratio, 1.24; 95% CI, 1.06-1.45; P = .008). CONCLUSIONS: Repair of secondary mitral regurgitation has an associated survival benefit compared with MV replacement.

Tricuspid leaflet kinematics after annular size reduction in ovine functional tricuspid regurgitation.

OBJECTIVE: Tricuspid annular size reduction with annuloplasty rings represents the foundation of surgical repair of functional tricuspid regurgitation. However, the precise effect of annular size reduction on leaflet motion and geometry remains unknown. METHODS: Ten sheep underwent surgical implantation of a pacemaker with an epicardial lead and were paced 200-240 beats/min to achieve biventricular dysfunction and functional tricuspid regurgitation. Subsequently, sonomicrometry crystals were implanted on the right ventricle, the tricuspid annulus, and on the belly of anterior, posterior, and septal tricuspid leaflets. Double-layer polypropylene suture was placed around the tricuspid annulus and externalized to a tourniquet. Simultaneous echocardiographic, hemodynamic, and sonomicrometry data were acquired with functional tricuspid regurgitation and during 5 consecutive annular reduction steps. Annular area, tenting height, and volume, together with each leaflet strain, radial length, and angles, were calculated from crystal coordinates. RESULTS: Rapid pacing reduced both left ventricle and right ventricle function and induced functional tricuspid regurgitation (0-3+) in all animals (from 0 ± 0 to 2.4 ± 0.7, P = .002), whereas tricuspid annulus diameter increased from 2.6 ± 0.3 cm to 3.3 ± 0.3 cm (P = .001). Tricuspid annular size reduction 1 to 5 resulted in 16% ± 7%, 37% ± 11%, 55% ± 11%, 66% ± 10%, and 76% ± 8% tricuspid annulus area reduction, respectively, and successively decreased tricuspid regurgitation. Tricuspid annular size reduction 2 to 5 induced anterior and posterior leaflet restricted motion and lower diastolic motion velocities. Tricuspid annular size reduction 5 perturbed septal leaflet range of motion but preserved its angle velocities. Tricuspid annular size reduction 3-5 generated compressive strains in all leaflets. CONCLUSIONS: Tricuspid annular area reduction of 55% perturbed anterior and posterior leaflet motion while maintaining normal septal leaflet movement. More extreme reduction triggered profound changes in anterior and posterior leaflet motion, suggesting that aggressive undersizing impairs leaflet kinematics.

Texas TriValve 1.0 : a reverse­engineered, open model of the human tricuspid valve.

Nearly 1.6 million Americans suffer from a leaking tricuspid heart valve. To make matters worse, current valve repair options are far from optimal leading to recurrence of leakage in up to 30% of patients. We submit that a critical step toward improving outcomes is to better understand the "forgotten" valve. High-fidelity computer models may help in this endeavour. However, the existing models are limited by averaged or idealized geometries, material properties, and boundary conditions. In our current work, we overcome the limitations of existing models by (reverse) engineering the tricuspid valve from a beating human heart in an organ preservation system. The resulting finite-element model faithfully captures the kinematics and kinetics of the native tricuspid valve as validated against echocardiographic data and others' previous work. To showcase the value of our model, we also use it to simulate disease-induced and repair-induced changes to valve geometry and mechanics. Specifically, we simulate and compare the effectiveness of tricuspid valve repair via surgical annuloplasty and via transcatheter edge-to-edge repair. Importantly, our model is openly available for others to use. Thus, our model will allow us and others to perform virtual experiments on the healthy, diseased, and repaired tricuspid valve to better understand the valve itself and to optimize tricuspid valve repair for better patient outcomes.

Long-Term Clinical Outcomes and Carotid Ultrasound Follow-Up of Transcarotid TAVI. Prospective Single-Center Registry.

This study aimed to prospectively evaluate the safety and long-term clinical outcomes of cerebral-oximetry-guided transcarotid transcatheter aortic valve implantation (TC-TAVI) with systematic follow-up with carotid ultrasound. Thirty-three TCTAVI procedures were performed in our center from 2017 to 2019. Our analysis includes in-hospital outcomes and long-term follow-up data on mortality, echocardiographic parameters, carotid Doppler ultrasound, and VARC-2 defined clinical events. Intraoperatively, one patient died, and one had a transient ischemic attack (TIA). The following events occurred in-hospital postoperatively: myocardial infarction (3.0%), cardiac tamponade (3.0%), new-onset atrial fibrillation (6.3%), need for temporary pacing (27.3%) and need for pacemaker implantation (15%). The mean follow-up was 19.5 ± 9.52 months. In the long-term follow-up, the two-year survival rate was 83% ± 14. The echocardiographic parameters did not differ significantly from the postprocedural values, and the ultrasound did not show any cases of significant vessel narrowing. The mean peak systolic velocity (PSV) was 71.6 cm/s in the left common carotid artery and 70.6 cm/s in the right common carotid artery. In conclusion, cerebral oximetry-guided TC access is safe, has a favorable long-term outcome, and does not increase the risk of plaque formation in the carotid artery. In a carefully selected group of patients, it might be considered as a first-choice alternative to TF access.

The effects of a simple optical clearing protocol on the mechanics of collagenous soft tissue.

Optical clearing of biological tissues improves imaging depth for light transmission imaging modalities such as two-photon microscopy. In studies that investigate the interplay between microstructure and tissue-level mechanics, mechanical testing of cleared tissue may be useful. However, the effects of optical clearing on soft tissue mechanics have not been investigated. Thus, we set out to quantify the effects of a simple and effective optical clearing protocol on the mechanics of soft collagenous tissues using ovine mitral valve anterior leaflets as a model system. First, we demonstrate the effectiveness of an isotonic glycerol-DMSO optical clearing protocol in two-photon microscopy. Second, we evaluate the mechanical effects of optical clearing on leaflets under equibiaxial tension in a dependent study design. Lastly, we quantify the shrinkage strain while traction-free and the contractile forces while constrained during clearing. We found the optical clearing protocol to improve two-photon imaging depth from ~100 µm to ~500-800 µm, enabling full-thickness visualization of second-harmonic generation, autofluorescent, and fluorophore-tagged structures. Under equibiaxial tension, cleared tissues exhibited reduced circumferential (p < 0.001) and radial (p = 0.009) transition stretches (i.e. stretch where collagen is recruited), and reduced radial stiffness (p = 0.031). Finally, during clearing we observed ~10-15% circumferential and radial compressive strains, and when constrained, ~2mN of circumferential and radial traction forces. In summary, we suggest the use of this optical clearing agent with mechanical testing be done with care, as it appears to alter the tissue's stress-free configuration and stiffness, likely due to tissue dehydration.

Long-term outcomes of etiology specific annuloplasty ring repair of ischemic mitral regurgitation.

BACKGROUND: Reductive annuloplasty repair of ischemic mitral regurgitation (IMR) is associated with high rates of recurrent MR, which may be improved with etiology-specific annuloplasty rings. METHODS: From October 2005 to May 2015, 128 consecutive patients underwent repair of IMR with the GeoForm ring. Clinical data was extracted from our local Society of Thoracic Surgeons database and electronic medical records. Mortality data was obtained from the Michigan State Social Security Death Index. RESULTS: The average age of patients was 65±11 years with mean pre-op left ventricular ejection fraction (LVEF) of 30%±10% and MR grade of 3.1±0.9 (0-4+). Thirty-day mortality was 4.7%, rate of renal failure 7.9%, rate of atrial fibrillation 27.3%, and no strokes were observed. Of the surviving patients, 89% (109/122) had a follow-up echocardiogram beyond 1 month with a mean echocardiographic follow-up of 59±39 months. LVEF improved from 30%±10% to 38%±14%, P<0.001) while end-diastolic (5.9±0.0 to 5.3±0.9 cm, P<0.001) and end-systolic (5.0±1.0 to 4.4±1.1 cm, P<0.001) left ventricular (LV) diameters decreased, as compared to pre-operative values. Seven patients were found to have recurrent moderate or greater IMR in follow-up to 10 years with three being due to ring dehiscence. One-, 5-, and 10-year freedom from recurrent moderate or severe IMR was 98%, 94%, and 80% respectively. One-, 5-, and 10-year survival was 91%, 77%, and 44%, respectively. CONCLUSIONS: Overall, etiology-specific ring repair of IMR was associated with low rates of recurrent MR on long-term follow-up, coupled with significant LV reverse remodeling and improvement in ejection fraction.