Epidemiology of Heart Valve Disease in Taiwan.

Studies conducted in developed nations have shown that increase in life expectancy has brought with it a rise in the incidence and treatment of degenerative aortic and mitral heart valve diseases. Current standards recommend valve replacement among even some asymptomatic patients. In this research, we examine the epidemiology of valvular heart disease and rate of valve replacement in Taiwan, where life expectancy now stands at 80.69 years. Patients were enrolled based on claims from a widely used national database and categorized into cohorts defined by type of valve disease and, further, by valve replacements and type of valve (mechanical, porcine, or bovine). Data, including disease type, age, and gender, were analyzed to determine annual and cumulative incidence rates and prosthetic usage from 2000 to 2017. Results showed that across the cohorts, the cumulative incidence rate in 2017 was 3.59%, and in the aortic valve cohort, the percentage of surgical valve replacement for those ≥60 years was 6.99%. Compared with other developed nations, this demonstrates that incidence rates are slightly higher, yet surgical replacements are less than half that of other developed nations. This under-treatment of patients with valvular heart disease presents an important public health challenge in Taiwan.

Contemporary Outcomes of Surgical Aortic Valve Replacement in Japan.

BACKGROUND: Given the rapid expansion in the use of transcatheter aortic valve implantation (TAVI), recent outcomes of surgical aortic valve replacement (SAVR) should be re-evaluated.Methods and Results:Using the data from the Japan Cardiovascular Surgery Database of 160 enrolled hospitals, trends in elective isolated SAVR were evaluated until the introduction of TAVI in Japan. Trend analyses were performed over 4 periods: period 1, 2008-2009 (4,415 cases); period 2, 2010-2011 (4,861 cases); period 3, 2012-2013 (5,674 cases); and period 4, 2014-2015 (5,563 cases). Baseline risk, evaluated on JapanSCORE, increased significantly over the 4 periods, from a median of 1.56 (IQR, 0.99-2.61) in period 1 to 2.08 (IQR, 1.33-3.96) in period 4 (P<0.001, trend test). Despite the increased risk, the composite major complication and operative mortality rate decreased significantly (10.7% in period 1 to 9.2% in period 4, P=0.01). Using a risk-adjusted model, the OR of operative mortality was 1.61 (95% CI: 1.29-2.02) in period 1 (P<0.0001) compared with period 4. An increase in the use of bioprostheses was also observed, from 60.4% to 76.8% (P<0.001) over the 4 periods. CONCLUSIONS: Even in a short 8-year period, SAVR outcomes improved in Japan. This should be taken into account when discussing the indications for aortic valve intervention.

Population trends in aortic valve surgery in Finland between 2001 and 2016.

Objectives. To investigate nationwide changes in procedure rates, patient selection, and prognosis after all surgical aortic valve replacements. Design. Patients undergoing primary surgical aortic valve replacement between 2001 and 2016 were identified from three nationwide registers with compulsory reporting to examine trends in aortic valve surgery over four four-year time periods. Results. A total of 12,139 surgical aortic valve replacement procedures (mean age 61.9 ± 11.8 years, 39.1% women) were performed. The total number of biological valves increased from 1001 (42.9%) to 2526 (75.5%) from 2001-2004 to 2013-2016 (p < .001). During the first and last time periods the comorbidity burden increased; share of patients with hypertension increased from 37.5% to 46.9% (p < .001), diabetes from 14% to 16.5% (p = .01) and previous stroke from 5.2% to 7.2% (p = .01). The proportion of women undergoing surgery decreased from 40% to 36.1% from 2001-2004 to 2013-2016, respectively (p = .01). Overall 28-day mortality was 3.5%. In patients with biologic valve the multivariable-adjusted risk of short-term mortality decreased steadily in every four-year period from 2001-2004 to 2005-2008 (HR, 0.66; 95% CI 0.47-9.92), 2009-2012 (HR, 0.54; 95% CI, 0.39-0.75) and 2013-2016 (HR, 0.41; 95% CI, 0.29-0.58), whereas short-term mortality remained similar in patients with mechanical valve. The risk of four-year postoperative mortality after all surgical aortic valve replacements stayed constant. Conclusions. The use of biologic aortic valve prosthesis has increased from 2001 to 2016. The proportion of women has declined markedly. The short-term mortality has decreased and the long-term mortality has stayed constant despite increasing comorbidity burden.

Biologic Grafts for Use in Pelvic Organ Prolapse Surgery: a Contemporary Review.

PURPOSE OF REVIEW: Pelvic organ prolapse (POP) is a common condition and there is a plethora of surgical techniques available to address this problem. We present a review of biologic grafts, including the latest literature to help guide a surgeon's choice on the type of biologic materials to augment repairs. RECENT FINDINGS: Since the 2019 Food and Drug Administration (FDA) ban on mesh, including xenograft, there is a sparsity of biologic graft products available for POP repairs. This has led to a significant decrease in surgical application. Surgeons must be familiar with the biochemical properties, processing, and clinical application of biologic grafts prior to use. They should also be familiar with alternative operative techniques that utilize autografts, although there is limited outcome data on these techniques. With heightened awareness of mesh and its complications, biologic grafts have made a resurgence. Surgeons must be well versed on their available options. Current literature is limited, and studies have not demonstrated superiority of biologic graft over native tissue repairs for prolapse. Nevertheless, there is a role for these types of biologic graft material in specific patient populations. Future studies are warranted.

Impact of type 2 diabetes mellitus in the utilization and in-hospital outcomes of surgical aortic valve replacement in Spain (2001-2015).

BACKGROUND: The aims of this study were to examine trends in the incidence and in-hospital outcomes of SAVR among T2DM patients from 2001 to 2015, to compare clinical variables among T2DM patients and matched non-T2DM patients hospitalized for SAVR and to identify factors associated with in-hospital mortality (IHM) among T2DM patients. METHODS: We performed a retrospective study using the Spanish National Hospital Discharge Database, 2001-2015. We included patients who had SAVR as the procedure in their discharge report. For each T2DM patient, we selected a sex-, age-, implanted valve type- and year-matched nondiabetic patient. RESULTS: We identified 78,223 patients who underwent SAVR (23.49% with T2DM). The prevalence of T2DM increased significantly (p < 0.001) from 16.7% in 2001-2003 to 23.5% in 2012-2015. The incidence of SAVR increased significantly from 28.99 cases in 2001 to 65.79 cases in 2015 per 100,000 individuals in the T2DM population. Using Poisson regression models, we found that the incidence of SAVR was 2.60 times higher among patients with T2DM than among those without diabetes (IRR 2.60; 95% CI 2.56-2.65). The incidence of mechanical SAVR among T2DM patients remained stable from 2001 to 2015, and bioprosthetic SAVR rose from 8.29 to 41.74 cases per 100,000 individuals in the T2DM patient population (p < 0.001). We matched 8835 and 9543 patients who underwent mechanical and bioprosthetic SAVR, respectively. IHM decreased over time in T2DM patients and non-T2DM patients (from 8.89% and 7.81% to 3.88% and 5.07%, respectively). IHM was significantly lower in T2DM patients than in nondiabetic subjects who underwent bioprosthetic SAVR (4.77% vs. 6.04%, p < 0.001), with similar results obtained for mechanical valves (7.11% and 7.77%). CONCLUSIONS: The incidence of SAVR was higher in T2DM patients, and the incidence of bioprosthetic SAVR increased significantly among T2DM subjects. IHM decreased over time, regardless of the existence or absence of T2DM and the valve type. IHM was significantly lower in T2DM patients than in nondiabetic patients who underwent bioprosthetic SAVR.

Different approaches to heart valve decellularization: A comprehensive overview of the past 30 years.

Xenogeneic decellularized heart valve scaffolds have the potential to overcome the limitations of existing bioprosthetic heart valves that have limited duration due to calcification and tissue degeneration phenomena. This article presents a review of 30 years of decellularization approaches adopted in cardiovascular tissue engineering, with a focus on the use, either individually or in combination, of different detergents. The safety and efficacy of cell-removal procedures are specifically reported and discussed, as well as the structure and biomechanics of the treated extracellular matrix (ECM). Detergent residues within the ECM, production of hyaluronan fragments, safe removal of cellular debris, and the persistence of the alpha-Gal epitope after the decellularization treatments are of particular interest as parameters for the identification of the best tissue for the manufacture of bioprostheses. Special attention has also been given to key factors that should be considered in the manufacture of the next generation of xenogeneic bioprostheses, where tissues must retain the ability to be remodeled and to grow in weight along with body reshaping.

Population trends in mitral valve surgery in Finland between 1997 and 2014: the finnish CVD register.

OBJECTIVES: Contemporary, nationwide data on trends in mitral valve surgery are scarce. Our aim was to investigate changes in procedure rates, patient selection, and post-procedural prognosis of open-heart mitral valve surgery in Finland. DESIGN: We combined data from three nationwide administrative registers with compulsory reporting. We identified patients who had undergone first-ever open-heart mitral valve surgery between 1997 and 2014 and followed them for adverse events. We examined trends in mitral valve surgery over three six-year time periods (1997-2002, 2003-2008, and 2009-2014). RESULTS: 3684 mitral valve procedures (mean age: 67.0 ± 10.9 years, 42.6% women) were performed in 1997-2014 in Finland. During this period, mitral valve repair operations became more common than replacements and we observed an increasing trend in the use of bioprosthetic valves. Between 1997-2002 and 2009-2014, the mean age of patients undergoing mitral valve surgery and the proportion of urgent surgeries increased (p < .001 for both). The proportion of women undergoing surgery decreased while the share of patients with hypertension (p = .023) or diabetes (p = .026) increased. The multivariable-adjusted risk of 28-day (hazard ratio, 0.55; 95% confidence interval, 0.37-0.83) and 6-year (hazard ratio, 0.80; 95% confidence interval, 0.67-0.97) post-operative mortality was lower in the last six-year period than in 1994-1998. CONCLUSIONS: Short- and long-term mortality of mitral valve surgery patients in Finland has decreased from 1997 to 2014 despite the patients being older and having more comorbidities. Understanding the changing characteristics and prognosis of these patients is important for the interpretation of previous and future cohort studies and trials.

Transcatheter Tricuspid Valve-in-Valve Implantation for the Treatment of Dysfunctional Surgical Bioprosthetic Valves: An International, Multicenter Registry Study.

BACKGROUND: Off-label use of transcatheter aortic and pulmonary valve prostheses for tricuspid valve-in-valve implantation (TVIV) within dysfunctional surgical tricuspid valve (TV) bioprostheses has been described in small reports. METHODS AND RESULTS: An international, multicenter registry was developed to collect data on TVIV cases. Patient-related factors, procedural details and outcomes, and follow-up data were analyzed. Valve-in-ring or heterotopic TV implantation procedures were not included. Data were collected on 156 patients with bioprosthetic TV dysfunction who underwent catheterization with planned TVIV. The median age was 40 years, and 71% of patients were in New York Heart Association class III or IV. Among 152 patients in whom TVIV was attempted with a Melody (n=94) or Sapien (n=58) valve, implantation was successful in 150, with few serious complications. After TVIV, both the TV inflow gradient and tricuspid regurgitation grade improved significantly. During follow-up (median, 13.3 months), 22 patients died, 5 within 30 days; all 22 patients were in New York Heart Association class III or IV, and 9 were hospitalized before TVIV. There were 10 TV reinterventions, and 3 other patients had significant recurrent TV dysfunction. At follow-up, 77% of patients were in New York Heart Association class I or II (P<0.001 versus before TVIV). Outcomes did not differ according to surgical valve size or TVIV valve type. CONCLUSIONS: TVIV with commercially available transcatheter prostheses is technically and clinically successful in patients of various ages across a wide range of valve size. Although preimplantation clinical status was associated with outcome, many patients in New York Heart Association class III or IV at baseline improved. TVIV should be considered a viable option for treatment of failing TV bioprostheses.

Subclinical bioprosthetic aortic valve thrombosis: clinical and translational implications.

PURPOSE OF REVIEW: A recently published study has alerted the cardiovascular community to the existence of a significant and previously unrecognized risk of subclinical valve thrombosis following implantation of surgical and catheter-based bioprosthetic valves. The purpose of this article is to review our current understanding of this new clinical entity and to identify unanswered questions and areas for future research. RECENT FINDINGS: Subclinical bioprosthetic valve thrombosis (BPVT) is a more common phenomenon than previously appreciated. It appears that the incidence of BPVT is higher following transcatheter aortic valve replacement compared with surgical aortic valve replacement. Four-dimensional computed tomography (CT) is the most sensitive imaging modality for detection of leaflet immobility and subclinical BPVT. Certain echocardiographic findings, such as increasing transaortic gradients, increased cusp thickness and abnormal cusp mobility, predict the presence of BPVT on four-dimensional CT. There is a growing body of evidence linking subclinical BPVT with premature valvular hemodynamic deterioration and structural valve degeneration. Furthermore, subclinical leaflet thrombosis may constitute a nidus for unrecognized subacute cerebral or other thromboembolic events. Oral anticoagulation seems effective in both the prevention and treatment of BPVT. SUMMARY: Subclinical valve thrombosis is an important and underappreciated cause of early bioprosthetic valve failure. Although several recent studies have improved our understanding of this newly recognized clinical entity, a number of questions remain unanswered. Further studies are warranted to elucidate the true incidence of subclinical BPVT, its clinical consequences, as well as the optimal antithrombotic regimen following bioprosthetic valve implantation. The subgroups of patients at highest risk of BPVT will need to be identified for risk stratification purposes. Several ongoing clinical trials will shed some light on these important issues.

The Carmat Bioprosthetic Total Artificial Heart Is Associated With Early Hemostatic Recovery and no Acquired von Willebrand Syndrome in Calves.

OBJECTIVES: To determine hemostasis perturbations, including von Willebrand factor (VWF) multimers, after implantation of a new bioprosthetic and pulsatile total artificial heart (TAH). DESIGN: Preclinical study SETTING: Single-center biosurgical research laboratory. PARTICIPANTS: Female Charolais calves, 2-to-6 months old, weighing 102-to-122 kg. INTERVENTIONS: Surgical implantation of TAH through a mid-sternotomy approach. MEASUREMENTS AND MAIN RESULTS: Four of 12 calves had a support duration of several days (4, 4, 8, and 10 days), allowing for the exploration of early steps of hemostasis parameters, including prothrombin time; coagulation factor levels (II, V, VII+X, and fibrinogen); and platelet count. Multimeric analysis of VWF was performed to detect a potential loss of high-molecular weight (HMW) multimers, as previously described for continuous flow rotary blood pumps. Despite the absence of anticoagulant treatment administered in the postoperative phase, no signs of coagulation activation were detected. Indeed, after an immediate postsurgery decrease of prothrombin time, platelet count, and coagulation factor levels, most parameters returned to baseline values. HMW multimers of VWF remained stable either after initiation or during days of support. CONCLUSIONS: Coagulation parameters and platelet count recovery in the postoperative phase of the Carmat TAH (Camat SA, Velizy Villacoublay Cedex, France) implantation in calves, in the absence of anticoagulant treatment and associated with the absence of decrease in HMW multimers of VWF, is in line with early hemocompatibility that is currently being validated in human clinical studies.

Trends in Surgical Aortic Valve Replacement in More Than 3,000 Consecutive Cases in the Era of Transcatheter Aortic Valve Implantations.

Objectives Biological prostheses for surgical aortic valve replacement (sAVR) are increasingly being considered in patients < 60 years of age. Likely, preserving the option of performing a transcatheter valve-in-valve (ViV) procedure in cases of structural valve deterioration has contributed to this development. We assessed the use pattern in sAVR over an 11-year period. Methods From 2002 through 2012, a total of 3,172 patients underwent sAVR at our center. Results Mean age was 70.4 ± 10.6 years and mortality was 1.9%. From 2002 to 2012, mean manufacturer given valve size increased from 22.8 ± 1.7 to 23.9 ± 2.0 mm (p < 0.001). Mean true internal diameter and effective orifice area increased from 19.6 to 20.3 mm (p = 0.027) and 1.41 to 1.56 cm(2) (p < 0.001), respectively. Use of mechanical valves decreased from 10.9 to 1.8% (p < 0.001), and patients were younger in 2012 than in 2002 (52.8 ± 16.5 vs. 41.0 ± 14.3 years; p = 0.028). Conclusion Profound change of use pattern in sAVR was observed as indication for biological prostheses became more liberal. Larger prostheses were implanted during the observational period. Especially in younger patients, optimal sizing is essential to preserve the option for subsequent ViV procedures.

Longevity after aortic root replacement: is the mechanically valved conduit really the gold standard for quinquagenarians?

BACKGROUND: The choice of the best conduit for root/ascending disease and its impact on longevity remain controversial in quinquagenarians. METHODS AND RESULTS: A total of 205 patients (men=155) between 50 and 60 years (mean, 55.7 ± 2.9 years) received either a stentless porcine xenoroot (n=78) or a mechanically valved composite prosthesis (n=127) between February 1998 and July 2011. Of these, 166 patients underwent root replacement for aneurysmal disease (porcine: 39% [n=65]; mechanical: 61% [n=101]; P=0.5), 25 for acute type A aortic dissection (porcine: 32% [n=8]; mechanical: 68% [n=17]; P=0.51), and 14 for endocarditis/iatrogenic injury involving the aortic root (6.4% [n=5] versus 7.1% [n=9]; P=1.0). The predominant aortic valve pathology was stenosis in 19% (n=38), regurgitation in 50% (n=102), combined valvular dysfunction in 26% (n=54), and normal aortic valve function in 5% (n=11). Concomitant procedures included coronary artery bypass grafting (13%), mitral valve repair (7%), and partial/complete arch replacement (12%/4%), with no significant differences between porcine and mechanical root replacement. Overall hospital mortality was 7.3%, with no difference between the 2 types of valve prostheses (7.7% for porcine and 7.1% for mechanical root replacement; P=1.0). Follow-up averaged 5.4 ± 3.7 years (1096 patient-years) and was 100% complete. Freedom from aorta-related reoperation at 12 years was not statistically different between the groups (porcine: 94.9% versus mechanical: 96.1%; P=0.73). Survival was equivalent between both groups, with a 5-year survival of 86 ± 3% (porcine: 88 ± 4%; mechanical: 85 ± 3%; P=0.96) and a 10-year survival of 76% (porcine: 80 ± 7%; mechanical: 75 ± 5%; P=0.84). The linearized mortality rate was 3.1%/patient-year (porcine: 2.9%/patient-year; mechanical: 3.2%/patient-year). CONCLUSIONS: In quinquagenerians, long-term survival after stentless porcine xenograft aortic root replacement is equivalent to that after a mechanical Bentall procedure. These results bring into question the predominance of mechanical composite conduits for root replacement in quinquagenerians, particularly in the current era of transcatheter valve-in-valve procedures for structural valve deterioration.

[History, present and future of biomaterials used for artificial heart valves]. / Rys historyczny, terazniejszosc i przyszlosc biomaterialów wykorzystywanych w sztucznych zastawkach serca.

Artificial heart valves can be classified into mechanical and biological. We have three types of mechanical heart valves: caged ball, tilting disc and bileaflet. Mechanical heart valves are made from various materials. They may be produced from metals, ceramics and polymers, e.g.: stainless steel, titanium, silicone, pyrolytic carbon. Biological valves are made from synthetic components (e.g.: PTFE, Dacron) and materials of biological origin (e.g.: cow pericardium, pig heart valve). We have also identified transcatheter aortic valve implantation (TAVI). TAVI may be produced from metals, ceramics and polymers (e.g.: stainless steel, titanium, Dacron) and biological material (e.g.: pig heart valve). This paper describes advantages and disadvantages of different types of artificial heart valves. The lifespan of mechanical valves is 20-30 years and they can be used for patients of any age. Mechanical valves have also disadvantages--anticoagulants are required to prevent thrombosis. Biological valves are made from natural materials, so they do not require prolonged anticoagulation. Their lifetime is 10-15 years, so they are offered to patients over 40 years. Another problem is the occurrence of calcification.

Diastolic properties of the Sorin Solo, ATS 3F, Edwards Prima Plus and Medtronic Freestyle stentless valves: an independent in-vitro comparison.

BACKGROUND AND AIM OF THE STUDY: Currently, little is known of the diastolic properties of stentless valves that affect stress and strain on leaflets and, hence, their durability. In a pressurized aortic root model, a series of in-vitro tests was conducted to determine how stentless valves behave in diastole, and how they adapt to different annulus-to-sinotubular junction (STJ) ratios. METHODS: Sixteen 25 mm stentless aortic valves (four each of the Sorin Solo, ATS 3F, Edwards Prima Plus and Medtronic FreeStyle) were sutured into a 32 mm Valsalva graft, suspending the commissures into the expandable region (42 mm). The neoaortic root was pressurized and the size of the STJ progressively reduced by wrapping the neocommissural ridge with Dacron rings. Endoscopic views and ultrasound imaging were used to observe the geometry of the leaflets, regurgitation, and the height and level of leaflet coaptation at different annulus-to-STJ ratios. RESULTS: Pericardial prostheses built to mimic a cylinder (ATS 3F and Sorin Solo) showed the greatest tolerance to STJ dilatation and a larger coaptation surface, but also a tendency to roll in on themselves in an italic S-shape if oversized. Valves built to mimic native aortic leaflets (porcine Prima Plus and Medtronic Freestyle) showed a reduced tolerance to STJ dilatation, resulting in regurgitation and a smaller coaptation surface, but also a reduced tendency to roll if oversized. CONCLUSION: Despite similar systolic performances, stentless prostheses behave differently during diastole. The 3F and Solo valves benefit from a better tolerance to STJ dilatation, while the Prima Plus and Freestyle benefit from a more stable shape of closure under conditions of oversizing.

Assessment of a novel stentless mitral valve using a pulsatile mitral valve simulator.

BACKGROUND AND AIM OF THE STUDY: The study aim was to develop a novel stentless mitral valve (SMV) and to evaluate its performance, using an original pulsatile simulator developed specifically to analyze the hydrodynamic function of the mitral valve. METHODS: The SMV developed at the authors' institution consists of two major components: a large anterior leaflet with commissures, and a small posterior leaflet. The valve is formed by suturing the leaflets (made from bovine pericardium) to a flexible (Duran) ring. The SMV, constructed with a 27 mm flexible ring, was installed into the mitral valve simulator, after which the four papillary flaps of the two leaflets were sutured to artificial papillary muscles. The artificial ventricle was driven pneumatically at a pulse rate of 70 beats/min, with a systolic fraction of 35%. The mean flow, aortic pressure, and atrial pressure were adjusted to 4.5 1/min, 120/80 mmHg, and 10 mmHg, respectively. A 27 mm mechanical valve (MEV; St. Jude Medical Inc.) was employed as a control. The hydrodynamic performance of the SMV and MEV were investigated and compared. An echo-Doppler study was also performed. RESULTS: The waveforms of the SMV and MEV showed a similar pattern. The mean transvalvular flow was 4.7 +/- 0.4 1/min for the SMV, and 3.55 +/- 0.13 1/min for the MEV (p < 0.001). Mitral regurgitation was 5.07 +/- 1.15 and 3.78 +/- 0.35 ml/beat, respectively (p < 0.05). Echocardiographic data indicated that the regurgitant jet towards the left atrial model was none or trivial for the SMV, and trivial for the MEV. CONCLUSION: Within the environment of the mitral valve simulator, the novel SMV prepared from bovine pericardium demonstrated excellent performance characteristics, and may represent a potential future alternative for bioprosthetic stented mitral valves.

Carpentier-Edwards Magna ease versus Magna valves: a comparison of in-vitro valve hydrodynamic performance.

BACKGROUND AND AIM OF THE STUDY: Previous studies have shown that the Carpentier-Edwards Magna (CEM) valve is an excellent bioprosthesis in terms of its systolic performance; indeed, it has been described as 'a stented valve with stentless performance'. However, valve performance is not only a matter of gradients; it is also necessary to evaluate the diastolic-phase performance. Previous in-vitro studies have shown that the CEM has an excessive total regurgitant volume. Hence, the study aim was to compare the hydrodynamics of the CEM, with the newly evolved version of this valve, the CEM Ease (CEME). METHODS: The CEM and CEME valves (both 21 mm) were tested in the aortic chamber (23 mm diameter) of the Sheffield pulse duplicator. The tests were carried out at increasing pulse rates (PR; 70-100 beats/min), and at each pulse rate the valve was tested at different stroke volumes (SVs; 45-65 ml). The forward-flow pressure drop, closing leakage volumes and effective orifice area (EOA) were recorded. RESULTS: The CEM and CEME valves showed a comparable systolic-phase performance, there being no significant differences in terms of transvalvular gradient, EOA and stroke work loss, regardless of the PR and SV. In fact, the new CEME exhibited a significantly improved diastolic performance, with the total regurgitant volume being significantly lower, due especially to a reduced leakage volume and, to a lesser extent, a reduced closing volume. CONCLUSION: The study results indicated that the new CEME valve would maintain the excellent systolic performance of the previous CEM model, but with a significantly improved diastolic performance.

[Limbal stem cells and their niche: implications for bioengineered tissue constructs]. / Limbusstammzellen und ihre nische: bedeutung für biotechnologischen gewebeersatz.

Regeneration and repair of corneal epithelium rely on a reservoir of unipotent progenitor cells, which is situated within the basal epithelial layer at the corneoscleral limbus. If these cells are lost, corneal surface integrity is disturbed, which may lead to a painful loss of vision. Since the late 1990s cultivated grafts of limbal epithelium are being used therapeutically. Limbal epithelial cells are obtained from the fellow eye or from an allogeneic donor, propagated in culture on different types of carriers, and subsequently transplanted. This process entails removal of progenitor cells from their natural environment. However, surrounding cells and extracellular matrix are widely believed to provide important stimuli for stem cell maintenance and for correct differentiation. Therefore, new approaches aim at providing this so-called stem cell niche ex vivo and following transplantation. Niche factors can also drive transdifferentiation of alternative progenitor cell types towards a corneal phenotype. This permits the use of autologous cells in cases of bilateral limbal stem cell insufficiency. Several biosynthetic substrates have been devised for culture, transdifferentiation and transplantation of donor cells. This work intends to provide an overview of constructs that are currently available and to some extent clinically employed. In addition, a summary is given of novel concepts which aim at integrating putative niche factors into the stem cell carriers to replicate the stem cell niche.