How To Do It: Mitral Valve Translocation.

Mitral valve translocation (MVT) is a novel procedure that was developed to treat patients with severe, symptomatic, secondary mitral regurgitation (MR). MVT enhances leaflet coaptation by insertion of an autologous pericardial patch interposed between the mitral annulus and the native mitral leaflets. The patch substantially increases total leaflet surface area and creates supranormal coaptation. In addition, it relieves leaflet tethering by transposing the native valve deeper into the ventricle and decreases the circumference of the annulus. The enhanced coaptation produced by MVT may protect against recurrent MR in patients with continued adverse left ventricular remodeling. The procedural steps include detachment of the intact native mitral valve at the annulus, placement of interrupted pledgeted sutures around the annulus to secure the proximal aspect of the patch, and attachment of the native valve to the distal aspect of the patch using running suture. Follow-up of patients who have undergoing MVT is ongoing, with satisfactory short-term results, including sustained MR grades of ≤mild and 14 mm coaptation at 12 months.

Effectiveness of telemedicine in a mitral valve center of excellence.

BACKGROUND: The COVID-19 pandemic necessitated a drastic increase in the use of telemedicine. There is little information about the effectiveness of telemedicine in cardiac surgery. We examined clinical outcomes and patient satisfaction among patients who had in-person versus telemedicine preoperative appointments in a subspecialized mitral valve surgical practice. METHODS: We retrospectively reviewed all patients who had elective mitral valve operations between January 2019 and February 2021. Patients were categorized into 2 groups based on the format of the preoperative appointment (telemedicine or in-person). Preoperative characteristics and clinical outcomes were compared between the two groups. All patients who had a telemedicine appointment were sent an online survey to assess their satisfaction with the process. RESULTS: Among 286 patients analyzed, 197 (69%) had in-person preoperative evaluations and 89 (31%) had telemedicine evaluations. The in-person and telemedicine groups had similar preoperative and operative characteristics. Outcomes did not differ between the 2 groups, including ventilation time (3.7 vs. 4.1 h, p = .399), total length of stay (5 vs. 5 days, p = .949), 30-day mortality (0% vs. 1%, p = .311), and readmissions within 30 days (13% vs. 8%, p = .197). Among patients who completed the survey, 91% were "satisfied" or "very satisfied" with the telemedicine preoperative appointment. CONCLUSION: Patients who had telemedicine preoperative appointments before mitral valve operations during the COVID-19 pandemic had similarly excellent clinical outcomes to patients who had in-person preoperative appointments before the pandemic. Patients had relatively high levels of satisfaction with telemedicine and almost half preferred telemedicine for future visits.

Intraoperative echocardiographic assessment of mitral valve translocation.

OBJECTIVES: The aim of this study was to present a rigorous method to analyse the intraoperative echocardiographic images from the novel mitral translocation procedure, which assesses the changes in mitral structure and function and compares this data to a control group of patients who have no mitral regurgitation (MR). METHODS: Transoesophageal echocardiography was post-processed using dedicated 3D software. Ten patients with normal mitral valves (MV) undergoing non-mitral cardiac surgery served as controls. Mitral coaptation area, mid-leaflet coaptation length and mitral annular circumference were measured in 3D. RESULTS: Twenty-three consecutive patients with severe secondary MR underwent MV translocation. All patients had none/trace MR post-translocation. The mean coaptation surface area increased from 63 to 427 mm2 (P < 0.001) and coaptation length increased from 1.0 to 10.5 mm (P < 0.001). The control group coaptation surface area (136 mm2) and length (2.5 mm) were greater than pre-translocation (P = 0.019; P < 0.001) and less than post-translocation (P < 0.001; P < 0.001). 3D mitral annular circumference in the translocation group decreased 15% (130-110 mm) (P < 0.001). Post-translocation, the mean gradient was 2(2-3) mmHg with the diastolic mitral orifice area of 3.4 ± 0.3 cm2 by planimetry and 3.5 ± 0.3 cm2 by pressure half-time. The coaptation to septum distance remained unchanged (P = 0.305) without systolic anterior leaflet motion. CONCLUSIONS: This echocardiographic analysis method demonstrates that MV translocation abolishes secondary MR, increases coaptation area and length and produces acceptable diastolic function. This method of analysis should allow precise structural and quantitative assessment of the durability of the repair in future long-term follow-up.

Quantitating Mitral Regurgitation in Clinical Trials: The Need for a Uniform Approach.

BACKGROUND: There is an established relationship between the degree of mitral regurgitation (MR) and prognosis. Quantitation of MR severity guides therapeutic approaches. Inconsistent definitions and categorization of MR severity in clinical studies limit meaningful comparisons among trials and compromise development of an effective evidence base. The purpose of this study was to quantify heterogeneity in grading systems for MR severity in the contemporary literature. METHODS: This was a systematic review of randomized controlled trials and propensity score-adjusted clinical studies of mitral valve interventions (surgical or percutaneous). A total of 35 articles from 2015 to 2020 were included (15 randomized controlled trials and 20 propensity score-adjusted clinical studies). RESULTS: There were 22 studies that reported MR severity in numeric categories, either values from the historical "plus" system or numeric MR grades, whereas 9 studies reported MR severity using text-only descriptive categories. Among the studies that used numeric categories, 2+ MR was defined as moderate in 64% of studies, mild in 27%, and mild-moderate in 9%, and 3+ MR was defined as moderate in 14%, moderate-severe in 52%, and severe in 14%. CONCLUSIONS: There was substantial variability in MR severity definition and reporting in contemporary clinical studies of mitral valve interventions. We recommend that the historical plus numeric grading system be abandoned and that inclusion and outcome criteria in MR clinical trials be based on US and European guideline-recommended categories as none or trace, mild, moderate, and severe. Adoption of these simple recommendations will improve the consistency and quality of MR clinical trial design and reporting.

Mitral Valve Translocation: Optimization of Patch Geometry in an Ex Vivo Model of Secondary Mitral Regurgitation.

Optimal translocation patch width for functional mitral regurgitation (FMR) treatment was evaluated in an air-filled ex vivo system. FMR was created in 19 isolated swine hearts by annular dilation and papillary muscle displacement. Frustum-shaped pericardial patches of varying widths (Group 1 = 0.5 cm; Group 2 = 1.0 cm; Group 3 = 1.5 cm) were implanted and imaged via a 3D-structured light scanner. Median leaflet coaptation decreased (P < 0.001) from 5.5 ± 2.0 mm at baseline to 2.4 ± 1.3 mm following FMR creation. Translocation repair increased coaptation length over FMR levels by 2.2 mm in Group 1 (P < 0.001), 4.6 mm in Group 2 (P < 0.001), and 4.7 mm in Group 3 (P < 0.001). After repair, no significant differences were found between groups for annular height, circularity index, tenting height, tenting area, and non-coapting surface area. The supranormal coaptation and minimal valve geometric changes support using a 1.0- or 1.5-cm translocation patch for FMR treatment. Implantation of a 1.0-cm or 1.5-cm circumferential pericardial patch (mitral valve translocation) increases leaflet coaptation length without significantly altering valve geometry.

Mitral Valve Translocation: A Novel Operation for the Treatment of Secondary Mitral Regurgitation.

BACKGROUND: Conventional annuloplasty repair of secondary (functional) ischemic mitral regurgitation (IMR) is associated with a 60% recurrence of moderate or greater mitral regurgitation at 2 years. We developed a novel repair technique for IMR that addresses the underlying geometric alterations of the mitral valve apparatus and compared outcomes with those of conventional repair in a swine model. METHODS: Chronic IMR was induced by percutaneous embolization of the circumflex artery. Swine with severe IMR (median 9 weeks after infarction) underwent undersized rigid annuloplasty (n = 5) or translocation repair (n = 6). Translocation repair consisted of detaching the mitral valve en bloc at the annulus, creating a 1 cm wide frustum-shaped pericardial patch, and suturing the outer circumference of the patch to the annulus and inner circumference to the mitral valve. RESULTS: Operative survival was 92% (11 of 12). All animals had none/trace residual central mitral regurgitation, and mean inflow gradients were similar (1 mm Hg [interquartile range, 1 to 2] vs 2 mm Hg [interquartile range, 1 to 2]; P = .75) in the annuloplasty and translocation groups, respectively. Median coaptation length marginally improved in conventional swine (3 to 4 mm, P = .05), but dramatically improved in translocation swine (3 to 8 mm, P = .003). Posterior leaflet angle increased from 39 to 80 degrees (P = .05) in annuloplasty swine but decreased from 50 to 31 degrees (P = .03) in translocation swine. The posterior leaflet was immobile after annuloplasty but had preserved motion after translocation (excursion, 1 degree vs 24 degrees; P = .045). CONCLUSIONS: Mitral valve translocation effectively treats mitral regurgitation by relieving leaflet tethering. Compared with annuloplasty, mitral valve translocation creates a larger surface of coaptation and preserves leaflet mobility without compromising diastolic function.

Transseptal Puncture Learning Curve for Transcatheter Edge-to-Edge Mitral Valve Repair.

OBJECTIVE: This study examined the learning curve for transseptal puncture (TSP) during transcatheter edge-to-edge mitral valve repair (TEER) performed by a dedicated mitral valve structural heart team. Effective TSP is mandatory for TEER but can be time-consuming and associated with complications including pericardial effusion and cardiac tamponade. METHODS: TSP was performed on 107 consecutive patients (76 ± 1 years, 52% male) undergoing TEER between 2014 and 2019. TSP was performed by each structural heart team member (1 cardiologist, 2 cardiac surgeons) on a rotating case-by-case basis. No team member had prior independent TSP experience. Data collected included total procedure time, TSP time (time elapsed between procedure start and septal crossing), and number of TSP attempts before successful puncture. Cumulative sum (CUSUM) of deviations from the mean across sequential cases were used to examine learning curves. RESULTS: Median total procedure time was 107 min, and the median TSP time was 14 min. Greater case number was significantly associated with both lower TSP time (r s = -0.22, P = 0.022) and lower total procedure time (r s = -0.29, P = 0.003). The majority of patients required only 1 TSP attempt (79%). There was a significant quadratic relationship between case number and the CUSUM for TSP time, with the learning curve peaking at 49 cases. CONCLUSIONS: TSP for TEER has a substantial learning curve, requiring >50 cases to achieve acceptable efficiency. Even once proficiency is demonstrated, TSP remains a time-consuming component of TEER. Improvements in transseptal access technology may significantly decrease the time needed to master TSP and may improve the safety and precision of the procedure.

Initial Clinical Experience With Mitral Valve Translocation for Secondary Mitral Regurgitation.

BACKGROUND: Functional (secondary) mitral regurgitation (FMR) results from altered geometry of the mitral valve apparatus. Repair with restrictive mitral annuloplasty is associated with high rates of recurrent mitral regurgitation (MR). We developed a novel operative repair for FMR that translocates the intact mitral valve towards the apex. METHODS: The mitral valve was detached circumferentially and translocated into the ventricle with a frustum-shaped glutaraldehyde-treated autologous pericardial patch. Clinical and echocardiographic follow-up was performed. RESULTS: Fifteen consecutive patients with FMR (mean age, 59 years; 67% female) had mitral valve translocation between 2018 and 2020. Preoperative mean ejection fraction, left ventricular end-diastolic dimension, and systolic pulmonary artery pressure were 40% ± 11%, 59 ± 8 mm, and 49 ± 21 mm Hg, respectively; 33% had atrial fibrillation. Cardiomyopathy was ischemic in 4 and nonischemic in 11. Concomitant procedures included tricuspid valve operation (n = 8), coronary artery bypass grafting (n = 4), and atrial fibrillation ablation (n = 5). Post bypass transesophageal echocardiogram demonstrated none/trace MR in all patients and mean gradient of 3 mm Hg (interquartile range, 2-4 mm Hg). Mean leaflet extent of coaptation was 14 ± 2 mm (range, 11-17 mm). There was no postoperative mortality, stroke, or renal failure. Predismissal echocardiography showed none/trace MR in 14 patients and mild MR in 1. One patient underwent successful late rerepair of a suture line leak. Twelve patients were alive at latest follow-up and MR at 1 and 6 months was mild or less in all patients with mean leaflet extent of coaptation of 14 ± 2 mm (range, 12-16 mm) at 6 months. CONCLUSIONS: Mitral valve translocation creates a large surface of coaptation and effectively corrects FMR. Further study is needed to demonstrate the long-term durability and clinical utility of this operation.

Development of a Reproducible Swine Model of Chronic Ischemic Mitral Regurgitation: Lessons Learned.

BACKGROUND: Durability of mitral valve repair for ischemic mitral regurgitation (IMR) remains poor. We established a swine model of chronic IMR, and describe the methods and lessons learned from this model. METHODS: Thirty-five swine underwent percutaneous myocardial infarction with ethanol ablation of the circumflex or obtuse marginal (OM) arteries. Swine were followed with routine echocardiography for the development of severe IMR. Once severe IMR was established, swine underwent mitral valve operations on cardiopulmonary bypass. After operation, swine were survived up to 7 weeks. Angiographic and echocardiographic features of swine who developed severe IMR (IMR swine) and those who did not (non-IMR swine) were compared. RESULTS: The median number of OM arteries was 3, with 2 OM arteries infarcted. Acute survival after the myocardial infarction was 74% (26 of 35) with 3 (9%) early, postoperative deaths. Among the 23 swine with follow-up to determine IMR status, 14 of 23 (61%) developed significant IMR. Among IMR pigs, left ventricular (LV) ejection fraction decreased from 65% pre-myocardial infarction to 45% pre-mitral valve intervention (P < .001). Among non-IMR swine, LV ejection fraction decreased nonsignificantly from baseline (60%) to latest follow-up (55%) (P = .443). LV end-diastolic dimension (P = .039), wall motion score (P = .027), global circumferential strain (P = .014), and global longitudinal strain (P = .023) were significantly worse in IMR compared with non-IMR swine. CONCLUSIONS: A reproducible percutaneous model of severe IMR in swine is feasible with a guided anesthetic and perioperative approach. This model can serve as a platform to better understand the mechanism of IMR and subsequently to test novel repair techniques.

Long-term Performance of Fresh Autologous Pericardium for Mitral Valve Leaflet Repair.

BACKGROUND: Glutaraldehyde-fixed autologous or bovine pericardial patches used for mitral valve leaflet reconstruction have been associated with late calcification. Fresh autologous pericardium (FAP) may be a durable alternative. METHODS: Transthoracic echocardiography was used to assess valve function (regurgitation, mean pressure gradient, patch pliability, and calcification) in patients undergoing FAP mitral leaflet repairs. Pliability was scored between 1 (similar to native leaflets) and 4 (rigid). Calcification was scored between 1 (echobrightness similar to native leaflets) and 4 (very bright). RESULTS: Between 2002 and 2018, 62 consecutive patients (50% male, 51 ± 2 years, 69% infective endocarditis) underwent mitral valve repair with FAP, and Patch placement was on the anterior (31 of 62), posterior (27 of 62), or both (1 of 62) leaflets. Late echocardiographic follow-up was available for 43 of 62 patients (median follow-up, 3.6 years; range, 0.5-6 years). Average pliability scores were unchanged between discharge (1.2 ± 0.1) and follow-up (1.2 ± 0.2, P = .79). Average brightness scores increased modestly (predischarge, 1.6 ± 0.1; follow-up, 1.8 ± 0.1; P = .01). Three patients had recurrent severe mitral regurgitation, and 2 underwent reoperation, 1 at 1 year postoperatively for recurrent endocarditis and 1 at 6 years postoperatively for degenerative disease progression. At reoperation, patches were pliable, free from calcification, and comparable in thickness to adjacent native leaflet. One patient developed suture line leak, which was repaired. No other evidence of patch dehiscence, retraction, or aneurysm was observed. The 10-year freedom from reoperation of 82% and survival rate of 84% are comparable to repair with glutaraldehyde-fixed or bovine pericardial patches. CONCLUSIONS: FAP is an excellent substrate for complex mitral valve leaflet patch repairs and can be used with the expectation of durable, long-term valve function, without evidence of late patch calcification, stiffness, or aneurysmal degeneration.

Isolated Mitral Valve Surgery: The Society of Thoracic Surgeons Adult Cardiac Surgery Database Analysis.

BACKGROUND: Data from The Society of Thoracic Surgeons Adult Cardiac Surgery Database were analyzed to identify trends in patient characteristics and outcomes of mitral valve operations in North America. METHODS: All patients with isolated primary mitral valve operations with or without tricuspid valve repair, surgical atrial fibrillation ablation, or atrial septal defect closure performed July 2011 to September 2016 were identified. A subgroup analysis assessed patients with degenerative leaflet prolapse (DLP). RESULTS: Isolated primary mitral valve operations were performed on 87,214 patients at 1,125 centers, increasing by 24% between 2011 (n = 14,442) and 2016 (n = 17,907). The most common etiology was DLP (60.7%); 4.3% had functional mitral regurgitation. Preoperatively, 47.3% of patients had an ejection fraction less than 60% and 34.2% had atrial fibrillation. Overall mitral valve repair rate was 65.6%, declining from 67.1% (2011) to 63.2% (2016; p < 0.0001). Repair rates were related to etiology (DLP, 82.5%; rheumatic, 17.5%). Of the 29,970 mitral valve replacements, 16.2% were preceded by an attempted repair. Repair techniques included prosthetic annuloplasty (94.3%), leaflet resection (46.5%), and artificial cord implantation (22.7%). Bioprosthetic valves were implanted with increasing frequency (2011, 65.4%; 2016, 75.8%; p < 0.0001). Less-invasive operations were performed in 23.0% and concomitant tricuspid valve repair in 15.7%. Unadjusted operative mortality was 3.7% (replacements) and 1.1% (repairs). CONCLUSIONS: Patients undergoing primary isolated mitral valve operations commonly have ventricular dysfunction, atrial fibrillation, and heart failure. Although contemporary outcomes are excellent, earlier guideline-directed referral and increased frequency and quality of repair may further improve results of mitral valve operations.

Species-specific effects of aortic valve decellularization.

Decellularized heart valves have great potential as a stand-alone valve replacement or as a scaffold for tissue engineering heart valves. Before decellularized valves can be widely used clinically, regulatory standards require pre-clinical testing in an animal model, often sheep. Numerous decellularization protocols have been applied to both human and ovine valves; however, the ways in which a specific process may affect valves of these species differently have not been reported. In the current study, the comparative effects of decellularization were evaluated for human and ovine aortic valves by measuring mechanical and biochemical properties. Cell removal was equally effective for both species. The initial cell density of the ovine valve leaflets (2036±673cells/mm2) was almost triple the cell density of human leaflets (760±386cells/mm2; p<0.001). Interestingly, post-decellularization ovine leaflets exhibited significant increases in biaxial areal strain (p<0.001) and circumferential peak stretch (p<0.001); however, this effect was not observed in the human counterparts (p>0.10). This species-dependent difference in the effect of decellularization was likely due to the higher initial cellularity in ovine valves, as well as a significant decrease in collagen crosslinking following the decellularization of ovine leaflets that was not observed in the human leaflet. Decellularization also caused a significant decrease in the circumferential relaxation of ovine leaflets (p<0.05), but not human leaflets (p>0.30), which was credited to a greater reduction of glycosaminoglycans in the ovine tissue post-decellularization. These results indicate that an identical decellularization process can have differing species-specific effects on heart valves. STATEMENT OF SIGNIFICANCE: The decellularized heart valve offers potential as an improved heart valve substitute and as a scaffold for the tissue engineered heart valve; however, the consequences of processing must be fully characterized. To date, the effects of decellularization on donor valves from different species have not been evaluated in such a way that permits direct comparison between species. In this manuscript, we report species-dependent variation in the biochemical and biomechanical properties of human and ovine aortic heart valve leaflets following decellularization. This is of clinical significance, as current regulatory guidelines required pre-clinical use of the ovine model to evaluate candidate heart valve substitutes.

Design and efficacy of a single-use bioreactor for heart valve tissue engineering.

Heart valve tissue engineering offers the promise of improved treatments for congenital heart disorders; however, widespread clinical availability of a tissue engineered heart valve (TEHV) has been hindered by scientific and regulatory concerns, including the lack of a disposable, bioreactor system for nondestructive valve seeding and mechanical conditioning. Here we report the design for manufacture and the production of full scale, functional prototypes of such a system. To evaluate the efficacy of this bioreactor as a tool for seeding, ovine aortic valves were decellularized and subjected to seeding with human mesenchymal stem cells (hMSC). The effects of pulsatile conditioning using cyclic waveforms tuned to various negative and positive chamber pressures were evaluated, with respect to the seeding of cells on the decellularized leaflet and the infiltration of seeded cells into the interstitium of the leaflet. Infiltration of hMSCs into the aortic valve leaflet was observed following 72 h of conditioning under negative chamber pressure. Additional conditioning under positive pressure improved cellular infiltration, while retaining gene expression within the MSC-valve interstitial cell phenotype lineage. This protocol resulted in a subsurface pilot population of cells, not full tissue recellularization. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 249-259, 2017.

Performance of allogeneic bioengineered replacement pulmonary valves in rapidly growing young lambs.

BACKGROUND: Cardiac allometric organ growth after pediatric valve replacement can lead to patient-prosthesis size mismatch and valve re-replacement, which could be mitigated with allogeneic decellularized pulmonary valves treated with collagen conditioning solutions to enhance biological and mechanical performance, termed "bioengineered valves." In this study, we evaluated functional, dimensional, and biological responses of these bioengineered valves compared with traditional cryopreserved valves implanted in lambs during rapid somatic growth. METHODS: From a consanguineous flock of 13 lambs, the pulmonary valves of 10 lambs (mean weight, 19.6 ± 1.4 kg) were replaced with 7 bioengineered valves or 3 classically cryopreserved valves. After 6 months, the 10 lambs with implanted valves and 3 untreated flock mates were compared by echocardiography, cardiac catheterization, and explant pathology. RESULTS: Increases in body mass, valve geometric dimensions, and effective orifice areas were similar in the 2 groups of lambs. The bioengineered valves had higher median cusp-to-cusp coaptation areas (34.6%; interquartile range, 21.00%-35.13%) and were more similar to native valves (43.4%; interquartile range, 42.59%-44.01%) compared with cryopreserved valves (13.2%; interquartile range, 7.07%-13.91%) (P = .043). Cryopreserved valves cusps, but not bioengineered valve cusps, were thicker than native valve cusps (P = .01). Histologically, cryopreserved valves demonstrated less than native cellularity, whereas bioengineered valves that were acellular at the time of surgery gained surface endothelium and subsurface myofibroblast interstitial cells in pulmonary artery, sinus wall, and cusp base regions. CONCLUSIONS: Biological valve conduits can enlarge via passive dilatation without matrix synthesis, but this would result in decreased cusp coaptational areas. Bioengineered valves demonstrated similar annulus enlargement as cryopreserved valves but usually retained larger areas of cuspal coaptation. Heat-shock protein 47-positive (collagen-synthesizing) cells were present in previously acellular bioengineered sinus walls and cusp bases, but rarely in more distal cusp matrices.