Differential gene expression of leaflet tissue in chronic ovine functional tricuspid regurgitation.

OBJECTIVES: Severe functional tricuspid regurgitation (FTR) is associated with subvalvular remodelling, but leaflet tissue alterations may also contribute. We set out to investigate molecular mechanisms driving leaflet remodelling in chronic ovine FTR. METHODS: Thirteen adult sheep (55 ± 4kg) underwent left thoracotomy, epicardial echocardiography, and pulmonary artery banding (PAB) to induce right heart failure and FTR. After 16 weeks, 13 banded (FTR) and 12 control (CTL) animals underwent median sternotomy for epicardial echocardiography and were subsequently sacrificed with each tricuspid leaflet tissue harvested for RNA-seq and histology. RESULTS: After 16 weeks, 7 animals developed severe, 2 moderate, and 4 mild tricuspid regurgitation (TR). Relative to CTL, FTR animals had increased PAP, TR, tricuspid annular diameter, and right atrial volume, while tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change decreased. FTR leaflets exhibited altered constituents and an increase in cellularity. RNA-seq identified 85 significantly differentially expressed genes (DEG) with 17, 53, and 127 within the anterior, posterior, and septal leaflets respectively. RRM2, PRG4, and CXCL8 (IL-8) were identified as DEGs across all leaflets and CXCL8 was differentially expressed between FTR severity grades. RRM2, PRG4, and CXCL8 significantly correlated with TAPSE, and this correlation was consistent regardless of the anatomical location of the leaflet. CONCLUSIONS: PAB in our ovine model resulted in RV failure and FTR. Leaflet RNA-seq identified several DEGs, specifically RRM2, PRG4, and CXCL8, with known roles in tissue remodelling. These data along with an overall increase in leaflet cellularity suggest tricuspid leaflets actively remodel in FTR.

Contemporary outcomes of surgical aortic valve replacement in patients referred for a transcatheter approach.

OBJECTIVES: The purpose of this study is to examine which patients referred to our structural valve clinic for potential transcatheter aortic valve replacement (TAVR) are receiving surgical aortic valve replacement (SAVR) whether due to unsuitable anatomy for TAVR versus other reasons. METHODS: Individuals referred for TAVR from January 2019 to March 2022, who ultimately underwent SAVR were examined, retrospectively. Patients were divided into 2 surgical groups: TAVR was technically unsuitable (SAVR-TU) and those in which TAVR was technically feasible (SAVR-TF). RESULTS: 215 patients referred for TAVR underwent SAVR with 61 (28.4%) patients in the SAVR-TU group and 154 (71.6%) in the SAVR-TF group. The SAVR-TU group were more commonly female (52.5% vs 23.4%, p < 0.0001), had a higher incidence of stroke at baseline (9.8% vs 2.0%, p = 0.017) were frailer (5-m gait 5.2 s vs 4.7 s, p = 0.0035), and had a higher Society of Thoracic Surgery risk score (2.2 vs 1.7, p = 0.04). In the SAVR-TU group, unsuitability for TAVR was due to inadequate aortic root anatomy (86.9%), and poor peripheral access (6.6%). In the SAVR-TF group, the most common reasons for SAVR referral were concomitant coronary artery disease (42.9%), bicuspid aortic valve disease (16.9%), and concomitant aortic aneurysm (10.4%). Overall, in-hospital mortality was 1.4% with no difference between both groups. One-year survival was 96.7%. CONCLUSION: Despite a higher trend of aortic stenosis being treated with TAVR, higher risk patients unsuitable for TAVR can have SAVR with excellent outcomes. Moreover, patients with AS and concomitant other pathology should be evaluated for cardiac surgery.

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.

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.

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.

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.

Papillary muscle approximation in chronic ovine functional tricuspid regurgitation.

OBJECTIVE: Isolated tricuspid ring annuloplasty remains the surgical standard for functional tricuspid regurgitation repair but offers suboptimal results when right ventricular dilation and remodeling along with papillary muscle displacement is present. Addressing subvalvular remodeling with papillary muscle approximation may improve clinical outcomes. METHODS: Functional tricuspid regurgitation and biventricular dysfunction were induced in 8 healthy sheep by rapid ventricular pacing (200-240 bpm) for 27 ± 6 days. Subsequently, animals underwent cardiopulmonary bypass for implantation of sonomicrometry crystals on the tricuspid annulus, right ventricle, and papillary muscle tips. Papillary approximation sutures were anchored between anterior-posterior and anterior-septal papillary muscles and externalized through right ventricular free wall to epicardial tourniquets. After weaning from cardiopulmonary bypass, sequential papillary muscle approximations were performed. Simultaneous hemodynamic, sonomicrometry, and echocardiographic data were collected at baseline and after each papillary muscle approximation. RESULTS: With rapid pacing, right ventricular fractional area change decreased from 59 ± 6% to 38 ± 8% (P < .001), whereas tricuspid annulus diameter increased from 2.4 ± 0.3 cm to 3.3 ± 0.6 cm (P = .003). Tricuspid regurgitation (0-4+) increased from +0 ± 0 to +3.3 ± 0.7 (P < .001). Both anterior-posterior and anterior-septal papillary muscle approximation significantly reduced functional tricuspid regurgitation from +3.3 ± 0.7 to +2 ± 0.5 and +1.9 ± 0.6, respectively (P < .001). Reduction of tricuspid insufficiency with both subvalvular interventions was associated with decreased distance of the anterior papillary muscle to the annular centroid. CONCLUSIONS: Papillary muscle approximations were effective in reducing severe ovine functional tricuspid regurgitation associated with right ventricular dilation and papillary muscle displacement. Further studies are needed to evaluate efficacy of this adjunct to ring annuloplasty in repair of severe functional tricuspid regurgitation.

Effect of papillary muscle approximation on acute ovine functional tricuspid regurgitation.

OBJECTIVES: Ring annuloplasty represents the standard surgical treatment, but offers suboptimal results in patients with severe functional tricuspid regurgitation. Addition of papillary muscles (PMs) approximation may improve clinical outcomes. METHODS: Eight healthy adult male sheep (56 ± 4 kg) underwent cardiopulmonary bypass and implantation of sonomicrometry crystals on the tricuspid annulus, PM tips and right ventricular (RV) free wall. Papillary muscles approximation sutures were anchored between anterior-posterior and anterior-septal PMs and their loose ends externalized through RV free wall to epicardial tourniquets. After weaning from cardiopulmonary bypass, acute right heart failure and tricuspid regurgitation were induced, and subsequent sequential anterior-posterior and anterior-septal PM approximations were performed. Echocardiographic, haemodynamic and sonomicrometry data were collected. RESULTS: Tricuspid regurgitation at baseline in eight sheep was none or trace in 3 and mild in 5, and after induction of acute right heart failure increased significantly to moderate in 5, moderately severe in 1 and severe in 2 (P = 0.011). RV pressure increased from 31 [28; 43] to 51 [47; 55] mmHg (P = 0.012). Anterior-posterior PM approximation decreased regurgitation grade to none or trace in 1, mild in 4 and moderate in 3 (P = 0.016) and reduced PM area from 208 [160; 241] to 108 [48; 181] mm2 (P = 0.008), and anterior-posterior PM distance from 18 [16; 20] to 10 [7; 13] mm (P = 0.037). Anterior-septal approximation also significantly reduced PM area but had no effect on regurgitation grade. CONCLUSIONS: Anterior-posterior but not anterior-septal PM approximation alleviated acute ovine tricuspid regurgitation. Selective PM approximation may offer better control of tricuspid regurgitation.

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.

Chronic Ovine Model of Right Ventricular Failure and Functional Tricuspid Regurgitation.

The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to suboptimal clinical results. We set out to establish a chronic ovine model of FTR and right heart failure to investigate the mechanisms of FTR. Twenty adult male sheep (6-12 months old, 62 ± 7 kg) underwent a left thoracotomy and baseline echocardiography. A pulmonary artery band (PAB) was placed and cinched around the main pulmonary artery (PA) to at least double the systolic pulmonary artery pressure (SPAP), inducing right ventricular (RV) pressure overload and signs of RV dilatation. PAB acutely increased the SPAP from 21 ± 2 mmHg to 62 ± 2 mmHg. The animals were followed for 8 weeks, symptoms of heart failure were treated with diuretics, and surveillance echocardiography was used to assess for pleural and abdominal fluid collection. Three animals died during the follow-up period due to stroke, hemorrhage, and acute heart failure. After 2 months, a median sternotomy and epicardial echocardiography were performed. Of the surviving 17 animals, 3 developed mild tricuspid regurgitation, 3 developed moderate tricuspid regurgitation, and 11 developed severe tricuspid regurgitation. Eight weeks of pulmonary artery banding resulted in a stable chronic ovine model of right ventricular dysfunction and significant FTR. This large animal platform can be used to further investigate the structural and molecular basis of RV failure and functional tricuspid regurgitation.

Septal annular dilation in chronic ovine functional tricuspid regurgitation.

INTRODUCTION: Annular reduction with prosthetic rings represents the current surgical treatment of functional tricuspid regurgitation (FTR). However, alterations of annular geometry and dynamics associated with FTR are not well characterized. METHODS: FTR was induced in 29 adult sheep with either 8 weeks of pulmonary artery banding (PAB, n = 15) or 3 weeks of tachycardia-induced cardiomyopathy (TIC, n = 14). Eight healthy sheep served as controls (CTL). At the terminal procedure, all animals underwent sternotomy, epicardial echocardiography, and implantation of sonomicrometry crystals on the tricuspid annulus (TA) and right ventricular free wall while on cardiopulmonary bypass. Simultaneous hemodynamic, sonomicrometry, and echocardiographic data were acquired after weaning from cardiopulmonary bypass and stabilization. Annular geometry and dynamics were calculated from 3-dimensional crystal coordinates. RESULTS: Mean FTR grade (0-4) was 3.2 ± 1.2 and 3.2 ± 0.5 for PAB and TIC, respectively, with both models of FTR associated with similar degree of right ventricular dysfunction (right ventricular fractional area contraction 38 ± 7% and 37 ± 9% for PAB and TIC, respectively). Left ventricular ejection fraction was significantly reduced in TIC versus baseline (33 ± 9%, vs 58 ± 4%, P = .0001). TA area was 651 ± 109 mm2, 881 ± 242 mm2, and 995 ± 232 mm2 for CTL, FTR, and TIC, respectively (P = .006) with TA area contraction of 16.6 ± 4.2%, 11.5 ± 8.0%, and 6.0 ± 4.0%, respectively (P = .003). Septal annulus increased from 33.8 ± 3.1 mm to 39.7 ± 6.4 mm and 43.1 ± 3.2 mm for CTL, PAB, and TIC, respectively (P < .0001). CONCLUSIONS: Ovine FTR was associated with annular dilation and reduced annular area contraction. Significant dilation of septal annulus was observed in both models of FTR. As tricuspid rings do not completely stabilize the septal annulus, continued remodeling may contribute to recurrent FTR after repair.

Valvular complex and tissue remodelling in ovine functional tricuspid regurgitation.

OBJECTIVES: Pathophysiology of function tricuspid regurgitation (FTR) is incompletely understood. We set out to comprehensively evaluate geometric and tissue remodelling of the tricuspid valve complex in ovine FTR. METHODS: Twenty adult sheep underwent left thoracotomy and pulmonary artery banding (PAB) to induce right heart pressure overload and FTR. After 8 weeks, 17 surviving animals and 10 healthy controls (CTL) underwent sternotomy, echocardiography and implantation of sonomicrometry crystals on right ventricle and tricuspid valvular apparatus. Haemodynamic and sonomicrometry data were acquired in all animals after weaning from cardiopulmonary bypass. Leaflet tissue was harvested for pentachrome histologic analysis and biomechanical testing. RESULTS: Animal weight was 62 ± 5 and 63 ± 3 kg for CTL and PAB, respectively (P = 0.6). At terminal procedure, systolic pulmonary artery pressure was 22 ± 3 and 40 ± 7 mmHg for CTL and PAB, respectively (P = 0.0001). The mean TR grade (+0-4) was 0.8 ± 0.4 and 3.2 ± 1.2 (P = 0.0001) for control and banded animals, respectively. Right ventricle volume (126 ± 13 vs 172 ± 34 ml, P = 0.0019), tricuspid annular area (651 ± 109 vs 865 ± 247 mm2, P = 0.037) and area between papillary muscle tips (162 ± 51 vs 302 ± 75 mm2, P = 0.001) increased substantially while systolic excursion of anterior leaflet decreased significantly (23.8 ± 6.1° vs 7.4 ± 4.5°, P = 0.001) with banding. Total leaflet surface area increased from 806 ± 94 to 953 ± 148 mm2 (P = 0.009), and leaflets became thicker and stiffer. CONCLUSIONS: Detailed analysis of the tricuspid valve complex revealed significant ventricular, annular, subvalvular and leaflet remodelling to be associated with ovine functional tricuspid regurgitation. Durable surgical repair of severe FTR may require a multi-level approach to the valvular apparatus.

Randomized Feasibility Trial of Prophylactic Radiofrequency Ablation to Prevent Atrial Fibrillation after Cardiac Surgery.

OBJECTIVE: Evaluate the feasibility of prophylactic radiofrequency isolation of the pulmonary veins, with left atrial appendage amputation, to reduce the incidence of postoperative atrial fibrillation (POAF) after cardiac surgery in patients aged 70 and older. METHODS: The Federal Food and Drug Administration granted an investigational device exemption to utilize a bipolar radiofrequency clamp for prophylactic pulmonary vein isolation in a limited, feasibility trial. Sixty-two patients without prior dysrhythmias, were prospectively randomized to undergo either their index cardiac surgical procedure, or bilateral pulmonary vein isolation and left atrial appendage amputation during their cardiac operation. The primary outcome was occurrence of in-hospital POAF. Subjects were on 24-hour telemetry until discharge. Dysrhythmias, any episode of atrial fibrillation > 30 seconds, were confirmed by electrophysiologists blinded to the study. RESULTS: Sixty patients, mean age 75 years and mean CHA2DS2-VASc score 4, were analyzed. Thirty-one patients randomized to control and twenty-nine to the treatment group. Majority of cases in each group were isolated CABG. No perioperative complications related to the treatment procedure, need for permanent pacemaker, or mortality occurred. The in-hospital incidence of POAF was 55% (17/31) in the control group and 7% (2/29) in the treatment group. (p<0.001) The control group had a significantly higher requirement for antiarrhythmic medications at discharge, 45% (14/31) vs 7% (2/29) in the treatment group (p<0.001). CONCLUSIONS: Prophylactic radiofrequency isolation of the pulmonary veins with left atrial appendage amputation, during the primary cardiac surgical operation, reduced the incidence of POAF in patients 70 years and older with no history of atrial arrhythmias.

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.

Del Nido Cardioplegia in Ascending Aortic Surgery.

Del Nido cardioplegia offers equivalent myocardial protection and clinical outcomes to blood cardioplegia in adult isolated CABG and valve patients, but the safety and efficacy of del Nido in complex cases with prolonged aortic cross-clamp times is still unknown. 443 patients at our center underwent replacement of the ascending aorta using either del Nido (n = 182) or blood (n = 261) cardioplegia. Two surgeons used del Nido exclusively and 6 used blood exclusively over the study period. Propensity matching of preoperative characteristics yielded 172 well matched pairs. Emergency and reoperative cases were included. Clinical data were extracted from our local database. Troponin levels were drawn at 12 hours postop in all patients. Rates of perioperative mortality (4.7% vs 5.2%), stroke (5.8% vs 7.0%), renal failure (11.6% vs 12.2%), atrial fibrillation (36.0% vs 31.4%), intra-aortic balloon pump insertion (2.3% vs1.2%), and extra corporeal membrane oxygenation use (4.7% vs 4.1%) did not differ between blood and del Nido groups. Postop Troponin T levels were 0.50[0.35, 0.86] ng/mL and 0.40[0.20, 0.70] ng/mL for blood and del Nido, respectively (P < 0.0001). Postop echocardiography was available in 333 of 344 (96.8%) patients, and there was no difference in change in EF from pre- to postop between blood 0.0[-6.0, 5.0]% and del Nido 0.0 [-6.0, 3.5]% (P = 0.201). Subgroup analysis of patients with aortic cross-clamp time greater than 180 minutes (blood = 77, del Nido = 27) revealed no difference in troponins, ejection fraction, or clinical outcomes. Five-year survival was 85.9[76.8, 91.7]% and 79.8[71.2, 86.1]% for blood and del Nido, respectively (P = 0.151). In ascending aortic surgery with prolonged operative times, no differences were observed in myocardial protection or clinical outcomes with the use of del Nido cardioplegia compared to blood cardioplegia.

Five-year Outcomes of the COMMENCE Trial Investigating Aortic Valve Replacement With RESILIA Tissue.

BACKGROUND: The COMMENCE trial was conducted to evaluate the safety and effectiveness of aortic valve replacement using a bioprosthesis with novel RESILIA tissue (Edwards Lifesciences). RESILIA tissue is incorporated in the INSPIRIS RESILIA aortic valve (Edwards Lifesciences). METHODS: Patients underwent clinically indicated surgical aortic valve replacement with a bovine pericardial bioprosthesis (model 11000A; Edwards Lifesciences) in a prospective, multinational, multicenter (n = 27), US Food and Drug Administration Investigational Device Exemption trial. Events were adjudicated by an independent clinical events committee, and echocardiograms were analyzed by an independent core laboratory. Outcomes through an observational period of 5 years are reported. RESULTS: Between January 2013 and March 2016, 689 patients received the study valve. Mean patient age was 66.9 ± 11.6 years; Society of Thoracic Surgeons Predicted Risk of Mortality was 2.0% ± 1.8%; and 23.8%, 49.9%, and 24.4% of patients were New York Heart Association functional class I, II, and III at baseline, respectively. Through December 11, 2020 the follow-up duration was 4.3 ± 1.4 years, and the completeness of follow-up over the observational period was 95.5%. Early (<30 days) all-cause mortality was 1.2%, stroke 1.6%, and major paravalvular leak 0.1%. Five-year actuarial freedom from all-cause mortality, structural valve deterioration, and all-cause reintervention were 89.2%, 100%, and 98.7%, respectively. At 5 years the effective orifice area was 1.6 ± 0.5 cm2, mean gradient was 11.5 ± 6.0 mm Hg, 97.8% of patients were class I/II, and 97.8% and 96.3% of patients had none/trace paravalvular and transvalvular regurgitation, respectively. CONCLUSIONS: The safety and hemodynamic performance of this aortic bioprosthesis with RESILIA tissue through 5 years are encouraging, with clinically stable hemodynamics, minimal regurgitation, and no evidence of structural valve deterioration.

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.

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.

Efficacy of del Nido cardioplegia in adult cardiac procedures with prolonged aortic crossclamp time.

OBJECTIVE: Equivalent myocardial protection and clinical outcomes have been shown with the use of del Nido cardioplegia (DC) compared with blood cardioplegia (BC) in adult isolated coronary artery bypass grafting and valve patients. However, its safety and efficacy in cardiac procedures with aortic crossclamp times >90 minutes is still unknown. METHODS: From May 2014 to September 2019, 2506 adult patients at our center underwent cardiac surgery requiring prolonged aortic crossclamp time defined as 90 minutes or longer. Myocardial protection was achieved with BC in 1955 patients and DC in 551 patients. Two surgeons used DC exclusively and 5 used blood exclusively over the study period. BC was delivered anterograde and retrograde whereas DC was delivered anterograde only. Propensity score matching of several preoperative characteristics, including primary cardiac pathology, yielded 526 well matched pairs. Emergency and reoperative cases were included. Troponin T levels were drawn at 12 hours postoperative in all patients. Clinical data were extracted from our local Society of Thoracic Surgeons database. Subgroup analyses were performed on the basis of crossclamp time stratification. RESULTS: For the propensity score-matched cohort, the median crossclamp time was longer in the BC compared with the DC group (114 [interquartile range (IQR), 100-145] minutes for DC vs 153 [IQR, 122-200] minutes for BC; P < .0001) whereas intraoperative peak glucose was higher with BC (173 [IQR, 147-200] g/dL for DC vs 197 [IQR, 171-228] g/dL for BC; P < .001). In addition, perioperative mortality (3.4% vs 3.0%; P = .7273), stroke (3.2% vs 2.1%; P = .2504), renal failure (6.5% vs 4.6%; P = .1767), atrial fibrillation (34% vs 31.4%, P = .3575), intra-aortic balloon pump use (5.3% vs 4.6%, P = .5694), and extracorporeal membrane oxygenation use (3.0% vs 2.9%, P = .8596) did not differ between DC and BC. Postoperative troponin T levels were 0.53 (IQR, 0.30-0.96) ng/mL and 0.62 (IQR, 0.38-1.07) ng/mL for DC and BC, respectively (P = .0024). Subgroup analysis revealed higher troponin T levels with DC for crossclamp times between 150 and 180 minutes. Survival rates at 1, 2, and 5 years were 93.3%, 91.1%, and 78.7% for DC and 94.5%, 91.8%, and 81.5% for BC, respectively (P = .5140). CONCLUSIONS: In adult cardiac surgical procedures with aortic crossclamp times >90 minutes, comparable myocardial protection, perioperative mortality and morbidity, and distant survival were observed with the use of DC compared with BC. Higher troponin levels were seen in DC patients with crossclamp times between 150 and 180 minutes, but this was not associated with increased mortality.