Left atrial geometry in an ovine ischemic mitral regurgitation model:implications for transcatheter mitral valve replacement devices with a left atrial anchoring mechanism

Abstract Background Transcatheter mitral valve replacement (TMVR) is a challenging, but promising minimally invasive treatment option for patients with mitral valve disease. Depending on the anchoring mechanism, complications such as mitral leaflet or chordal disruption, aortic valve disruption or left ventricular outflow tract obstruction may occur. Supra-annular devices only anchor at the left atrial (LA) level with a low risk of these complications. For development of transcatheter valves based on LA anchoring, animal feasibility studies are required. In this study we sought to describe LA systolic and diastolic geometry in an ovine ischemic mitral regurgitation (IMR) model using magnetic resonance imaging (MRI) and echocardiography in order to facilitate future research focusing on TMVR device development for (I)MR with LA anchoring mechanisms. Methods A group of 10 adult male Dorsett sheep underwent a left lateral thoracotomy. Posterolateral myocardial infarction was created by ligation of the left circumflex coronary artery, the obtuse marginal and diagonal branches. MRI and echocardiography were performed at baseline and 8 weeks after myocardial infarction (MI). Results Six animals survived to 8 weeks follow-up. All animals had grade 2 + or higher IMR 8 weeks post-MI. All LA geometric parameters did not change significantly 8 weeks post-MI compared to baseline. Diastolic and systolic interpapillary muscle distance increased significantly 8 weeks post-MI. Conclusions Systolic and diastolic LA geometry do not change significantly in the presence of grade 2 + or higher IMR 8 weeks post-MI. These findings help facilitate future tailored TMVR device development with LA anchoring mechanisms

Descemet Membrane Endothelial Keratoplasty versus Ultrathin Descemet Stripping Automated Endothelial Keratoplasty A Multicenter Randomized Controlled Clinical Trial

Purpose: To compare best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD), refractive astigmatism, and complications after Descemet membrane endothelial keratoplasty (DMEK) and ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK). Design: Prospective, multicenter randomized controlled trial. Participants: Fifty-four pseudophakic eyes of 54 patients with corneal endothelial dysfunction resulting from Fuchs endothelial corneal dystrophy were enrolled in 6 corneal centers in The Netherlands. Methods: Participants were allocated to DMEK (n = 29) or UT-DSAEK (n = 25) using minimization randomization based on preoperative BSCVA, recipient central corneal thickness, gender, age, and institution. Donor corneas were prestripped and precut for DMEK and UT-DSAEK, respectively. Six corneal surgeons participated in this study. Main Outcome Measures: The primary outcome measure was BSCVA at 12 months after surgery. Results: Central graft thickness of UT-DSAEK lamellae measured 101 mu m (95% confidence interval [CI], 90-112 mu m). Best spectacle-corrected visual acuity did not differ significantly between DMEK and UT-DSAEK groups at 3 months (0.15 logarithm of the minimum angle of resolution [logMAR] [95% CI 0.08-0.22 logMAR] vs. 0.22 logMAR [95% CI 0.16-0.27 logMAR]; P = 0.15), 6 months (0.11 logMAR [95% CI 0.05-0.17 logMAR] vs. 0.16 logMAR [95% CI 0.12-0.21 logMAR]; P = 0.20), and 12 months (0.08 logMAR [95% CI 0.03-0.14 logMAR] vs. 0.15 logMAR [95% CI 0.10-0.19 logMAR]; P = 0.06). Twelve months after surgery, the percentage of eyes reaching 20/25 Snellen BSCVA was higher in DMEK compared with UT-DSAEK (66% vs. 33%; P = 0.02). Endothelial cell density did not differ significantly 12 months after DMEK and UT-DSAEK (1870 cells/mm 2 [95% CI 1670-2069 cells/mm(2)] vs. 1612 cells/mm(2) [95% CI 1326-1898 cells/mm(2)]; P = 0.12). Both techniques induced a mild hyperopic shift (12 months: +0.22 diopter [D; 95% CI -0.23 to 0.68 D] for DMEK vs. +0.58 D [95% CI 0.13-1.03 D] for UT-DSAEK; P = 0.34). Conclusions: Descemet membrane endothelial keratoplasty and UT-DSAEK did not differ significantly in mean BSCVA, but the percentage of eyes achieving 20/25 Snellen vision was significantly higher with DMEK. Endothelial cell loss did not differ significantly between the treatment groups, and both techniques induced a minimal hyperopic shift. (C) 2020 by the American Academy of Ophthalmolog

Quality of vision and vision-related quality of life after Descemet membrane endothelial keratoplasty:a randomized clinical trial

PURPOSE: To compare quality of vision and vision‐related quality of life (QOL) in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) or ultrathin Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Fifty‐four eyes of 54 patients with Fuchs' dystrophy from six corneal clinics in the Netherlands were randomized to DMEK or ultrathin DSAEK and examined preoperatively, and 3, 6 and 12 months postoperatively. Main outcome measures were corneal higher‐order aberrations (HOAs), contrast sensitivity, straylight and vision‐related QOL. RESULTS: Posterior corneal HOAs decreased after DMEK and increased after ultrathin DSAEK (p ≤ 0.001) 3 months after surgery and correlated positively with best spectacle‐corrected visual acuity (12 months: r = 0.29, p = 0.04). Anterior and total corneal HOAs did not differ significantly between both techniques at any time point. Contrast sensitivity was better (p = 0.01), and straylight was lower (p = 0.01) 3 months after DMEK compared with ultrathin DSAEK; 95% confidence interval [CI] of log(cs) 1.10–1.35 versus 95% CI: 0.84 to 1.12, and 95% CI: log(s) 1.18 to 1.43 versus 95% CI: 1.41 to 1.66, respectively. Both were comparable at later time points. Vision‐related QOL (scale 0–100) did not differ significantly between both groups at any time point and improved significantly at 3 months (β = 12 [95% CI: 7 to 16]; p < 0.001), and subsequently between 3 and 12 months (β = 5 [95% CI: 0 to 9]; p = 0.06). CONCLUSIONS: Descemet membrane endothelial keratoplasty (DMEK) results in lower posterior corneal HOAs compared with ultrathin DSAEK. Contrast sensitivity and straylight recover faster after DMEK but reach similar levels with both techniques at 1 year. Vision‐related QOL improved significantly after surgery, but did not differ between both techniques

Trial-based cost-effectiveness analysis of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) versus DSAEK

Purpose: To evaluate the cost-effectiveness of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) versus standard DSAEK. Methods: A cost-effectiveness analysis using data from a multicentre randomized clinical trial was performed. The time horizon was 12 months postoperatively. Sixty-four eyes of 64 patients with Fuchs’ endothelial dystrophy were included and randomized to UT-DSAEK (n = 33) or DSAEK (n = 31). Relevant resources from healthcare and societal perspectives were included in the cost analysis. Quality-adjusted life years (QALYs) were determined using the Health Utilities Index Mark 3 questionnaire. The main outcome was the incremental cost-effectiveness ratio (ICER; incremental societal costs per QALY). Results: Societal costs were €9431 (US$11 586) for UT-DSAEK and €9110 (US$11 192) for DSAEK. Quality-adjusted life years (QALYs) were 0.74 in both groups. The ICER indicated inferiority of UT-DSAEK. The cost-effectiveness probability ranged from 37% to 42%, assuming the maximum acceptable ICER ranged from €2500–€80 000 (US$3071–US$98 280) per QALY. Additional analyses were performed omitting one UT-DSAEK patient who required a regraft [ICER €9057 (US$11 127) per QALY, cost-effectiveness probability: 44–62$29 271) per QALY, cost-effectiveness probability: 36–59%]. Furthermore, the ICER was €2101 (US$2581) per patient with clinical improvement in best spectacle-corrected visual acuity (≥0.2 logMAR) and €3274 (US$4022) per patient with clinical improvement in National Eye Institute Visual Functioning Questionnaire-25 composite score (≥10 points). Conclusion: The base case analysis favoured DSAEK, since costs of UT-DSAEK were higher while QALYs were comparable. However, additional analyses revealed no preference for UT-DSAEK or DSAEK. Further cost-effectiveness studies are required to reduce uncertainty

Long-term survival after mitral valve surgery for post-myocardial infarction papillary muscle rupture

Background: Papillary muscle rupture (PMR) is a rare, but dramatic mechanical complication of myocardial infarction (MI), which can lead to rapid clinical deterioration and death. Immediate surgical intervention is considered the optimal and most rational treatment, despite high risks. In this study we sought to identify overall long-term survival and its predictors for patients who underwent mitral valve surgery for post-MI PMR. Methods: Fifty consecutive patients (mean age 64.7 +/- 10.8 years) underwent mitral valve repair (n = 10) or replacement (n = 40) for post-MI PMR from January 1990 through May 2014. Clinical data, echocardiographic data, catheterization data, and surgical data were stored in a dedicated database. Follow-up was obtained in June of 2014; mean follow-up was 7.1 +/- 6.8 years (range 0.0-22.2 years). Univariate and multivariate Cox proportional hazard regression analyses were performed to identify predictors of long-term survival. Kaplan-Meier curves were compared with the log-rank test. Results: Kaplan-Meier cumulative survival at 1, 5, 10, 15, and 20 years was 71.9 +/- 6.4%, 65.1 +/- 6.9%, 49.5 +/- 7.6%, 36.1 +/- 8.0% and 23.7 +/- 9.2%, respectively. Univariate and multivariate analyses revealed logistic EuroSCORE >= 40% and EuroSCORE II >= 25% as strong independent predictors of a lower overall long-term survival. After removal of the EuroSCOREs from the model, preoperative inotropic drug support and mitral valve replacement (MVR) without (partial or complete) preservation of the subvalvular apparatus were independent predictors of a lower overall long-term survival. Conclusions: Logistic EuroSCORE >= 40%, EuroSCORE II >= 25%, preoperative inotropic drug support and MVR without (partial or complete) preservation of the subvalvular apparatus are strong independent predictors of a lower overall long-term survival in patients undergoing mitral valve surgery for post-MI PMR. Whenever possible, the subvalvular apparatus should be preserved in these patients

Genome-wide association study reveals novel genetic loci:a new polygenic risk score for mitral valve prolapse

AIMS: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder. METHODS AND RESULTS: We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors. CONCLUSION: We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-beta signalling molecules and spectrin beta. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention. KEY QUESTION: Expand our understanding of the genetic basis for mitral valve prolapse (MVP). Uncover relevant pathways and target genes for MVP pathophysiology. Leverage genetic data for MVP risk prediction. KEY FINDING: Sixteen genetic loci were significantly associated with MVP, including 13 novel loci. Interesting target genes at these loci included LTBP2, TGFB2, ALKP3, BAG3, RBM20, and SPTBN1. A risk score including clinical factors and a polygenic risk score, performed best at predicting MVP, with an area under the receiver operating characteristics curve of 0.677. TAKE-HOME MESSAGE: Mitral valve prolapse has a polygenic basis: many genetic variants cumulatively influence pre-disposition for disease. Disease risk may be modulated via changes to transforming growth factor-beta signalling, the cytoskeleton, as well as cardiomyopathy pathways. Polygenic risk scores could enhance the MVP risk prediction

A technique to excise the descemet membrane from a recipient cornea (descemetorhexis)

To describe a technique for excision of the Descemet membrane (DM) from the recipient eye for preparation of a recipient stromal bed in posterior lamellar keratoplasty. In 10 human eye bank eyes and 3 patients, recipient eyes had a 5.0-mm scleral tunnel incision made extending 1.0 mm into the peripheral cornea at the 12 o'clock surgical position. The anterior chamber was completely filled with air, and a reflective glide was placed through the incision onto the iris, to better visualize DM. A 9.0-mm mark was made onto the corneal epithelium to outline the area from which the Descemet membrane was to be removed. With a custom-made scraper, the DM was then carefully stripped off the posterior stroma by loosening the membrane at the 6 o'clock position and pulling it toward the incision at 12 o'clock. The excised DMs were evaluated by light and electron microscopy. In all recipient eyes, DM could be easily and completely removed from the posterior corneal stroma. Microscopy showed isolated DMs without stromal tissue elements. With the technique described, DM can be excised in a controlled fashion without damaging the posterior corneal stroma, to quickly create a recipient stromal bed before implantation of a donor posterior lamellar disk in posterior lamellar keratoplast

INTRACORNEAL AND SCLERAL CYST FOLLOWING CATARACT EXTRACTION

Background. A six-year-old boy presented with a large progressive intracorneal and scleral cyst. Two years before, bilateral cataract surgery through a 6.5-mm corneal incision was performed elsewhere.Methods. The posterior wall of the cyst could be excised, as well as the anterior wall in the sclera. Upon histo-pathology the cyst wall was lined by epithelium. The epithelial cells of the anterior side in the cornea were removed with a curette and a corpus alienum drill. Three and a half years after removal of the cyst, there was no recurrence. Visual acuity was 0.8. Conclusions. An intracorneal and scleral inclusion cyst was successfully removed by surgical excision and the removal of epithelial cells by a curette and a corpus alienum drill.</p