Characterisation and cross-amplification of 42 microsatellite markers in two Amphiprion species (Pomacentridae) and a natural hybrid anemonefish to inform genetic structure within a hybrid zone.

The hybrid anemonefish, Amphiprion leucokranos, is known to be the product of ongoing, introgressive hybridization between parent taxa Amphiprion sandaracinos and Amphiprion chrysopterus. Hybridization is an important evolutionary phenomenon contributing to biodiversity within marine systems, where hybrid zones provide ideal systems in which to study hybridization events. Here, a suite of 42 Amphiprion microsatellite markers (including development of 8 novel markers) were cross-amplified in individuals from parent taxa and hybrid populations to facilitate investigation into the relatedness of hybridizing species across the A. leucokranos hybrid zone. Analysis revealed 15, 20 and 24 highly polymorphic loci (PIC > 0.5) in the two parent species and hybrid, respectively, for use in population genetic and parentage studies, with 305 unique alleles found overall (ranging from 1 to 13 alleles per locus) and 7 alleles per locus on average. Observed and expected heterozygosities ranged from 0.000 to 1.000 and 0.000 to 0.978, respectively. Significant deviations from Hardy-Weinberg equilibrium were found in eight loci, possibly due to relatedness among samples or the presence of null alleles. Use of the suite of markers tested here will provide valuable insights into the contemporary population structure and introgression among species and hybrids within the Amphiprion leucokranos hybrid zone, as well as inform future ecological and evolutionary studies of anemonefishes more broadly.

Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery: a randomised trial.

Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre, randomised, double-blind, placebo-controlled DExamethasone for Cardiac Surgery (DECS) trial were followed up for 12 months after their cardiac surgical procedure. In the DECS trial, patients received a single intra-operative dose of dexamethasone 1 mg.kg-1 (n = 2239) or placebo (n = 2255). The effects on the incidence of major postoperative events were evaluated. Also, overall costs for the 12-month postoperative period, and cost effectiveness, were compared between groups. Of 4494 randomised patients, 4457 patients (99%) were followed up until 12 months after surgery. There was no difference in the incidence of major postoperative events, the relative risk (95%CI) being 0.86 (0.72-1.03); p = 0.1. Treatment with dexamethasone reduced costs per patient by £921 [€1084] (95%CI £-1672 to -137; p = 0.02), mainly through reduction of postoperative respiratory failure and duration of postoperative hospital stay. The probability of dexamethasone being cost effective compared with placebo was 97% at a threshold value of £17,000 [€20,000] per quality-adjusted life year. We conclude that intra-operative high-dose dexamethasone did not have an effect on major adverse events at 12 months after cardiac surgery, but was associated with a reduction in costs. Routine dexamethasone administration is expected to be cost effective at commonly accepted threshold levels for cost effectiveness.

Hierarchical behaviour, habitat use and species size differences shape evolutionary outcomes of hybridization in a coral reef fish.

Hybridization is an important evolutionary process, with ecological and behavioural factors influencing gene exchange between hybrids and parent species. Patterns of hybridization in anemonefishes may result from living in highly specialized habitats and breeding status regulated by size-based hierarchal social groups. Here, morphological, ecological and genetic analyses in Kimbe Bay, Papua New Guinea, examine the hybrid status of Amphiprion leucokranos, a nominal species and presumed hybrid between Amphiprion sandaracinos and Amphiprion chrysopterus. We test the hypothesis that habitat use and relative size differences of the parent species and hybrids determine the patterns of gene exchange. There is strong evidence that A. leucokranos is a hybrid of smaller A. sandaracinos and larger A. chrysopterus, where A. chrysopterus is exclusively the mother to each hybrid, based on mtDNA cytochrome b and multiple nDNA microsatellite loci. Overlap in habitat, depth and host anemone use was found, with hybrids intermediate to parents and cohabitation in over 25% of anemones sampled. Hybrids, intermediate in body size, colour and pattern, were classified 55% of the time as morphologically first-generation hybrids relative to parents, whereas 45% of hybrids were more A. sandaracinos-like, suggesting backcrossing. Unidirectional introgression of A. chrysopterus mtDNA into A. sandaracinos via hybrid backcrosses was found, with larger female hybrids and small male A. sandaracinos mating. Potential nDNA introgression was also evident through distinct intermediate hybrid genotypes penetrating both parent species. Findings support the hypothesis that anemonefish hierarchical behaviour, habitat use and species-specific size differences determine how hybrids form and the evolutionary consequences of hybridization.

The Dutch hospital standardised mortality ratio (HSMR) method and cardiac surgery: benchmarking in a national cohort using hospital administration data versus a clinical database.

OBJECTIVE: To compare the accuracy of data from hospital administration databases and a national clinical cardiac surgery database and to compare the performance of the Dutch hospital standardised mortality ratio (HSMR) method and the logistic European System for Cardiac Operative Risk Evaluation, for the purpose of benchmarking of mortality across hospitals. METHODS: Information on all patients undergoing cardiac surgery between 1 January 2007 and 31 December 2010 in 10 centres was extracted from The Netherlands Association for Cardio-Thoracic Surgery database and the Hospital Discharge Registry. The number of cardiac surgery interventions was compared between both databases. The European System for Cardiac Operative Risk Evaluation and hospital standardised mortality ratio models were updated in the study population and compared using the C-statistic, calibration plots and the Brier-score. RESULTS: The number of cardiac surgery interventions performed could not be assessed using the administrative database as the intervention code was incorrect in 1.4-26.3%, depending on the type of intervention. In 7.3% no intervention code was registered. The updated administrative model was inferior to the updated clinical model with respect to discrimination (c-statistic of 0.77 vs 0.85, p<0.001) and calibration (Brier Score of 2.8% vs 2.6%, p<0.001, maximum score 3.0%). Two average performing hospitals according to the clinical model became outliers when benchmarking was performed using the administrative model. CONCLUSIONS: In cardiac surgery, administrative data are less suitable than clinical data for the purpose of benchmarking. The use of either administrative or clinical risk-adjustment models can affect the outlier status of hospitals. Risk-adjustment models including procedure-specific clinical risk factors are recommended.

The role of exercise echocardiography in the management of mitral valve disease.

PURPOSE: Exercise echocardiography can assess the dynamic component of mitral valve (MV) disease and may therefore be helpful for the clinical decision-making by the heart team. The purpose of this study is to determine the role of exercise echocardiography in the management of disproportionately symptomatic or otherwise atypical patients with mitral regurgitation (MR) and stenosis (MS) in clinical practice. METHODS: Data of 14 MR and 14 MS patients, including echocardiograms at rest, were presented retrospectively to an experienced heart team to determine treatment strategy. Subsequently, exercise echo data were provided whereupon once again the treatment strategy was determined. This resulted in: value of exercise echo by means of 1) alteration or 2) confirmation of treatment strategy or 3) no additional value. RESULTS: During exercise the echocardiographic severity of MV disease increased in 9 (64 %) MR and 8 (57 %) MS patients. Based upon alteration or confirmation of the treatment strategy, the value of exercise echocardiography in the management of MR and MS was 86 % and 57 %, respectively. CONCLUSION: This study showed that physical exercise echo can have an important role in the clinical decision-making of challenging patients with MV disease. Exercise echocardiography had additional value to the treatment strategy in 71 % of these patients.

Long-term panmixia in a cosmopolitan Indo-Pacific coral reef fish and a nebulous genetic boundary with its broadly sympatric sister species.

Phylogeographical studies have shown that some shallow-water marine organisms, such as certain coral reef fishes, lack spatial population structure at oceanic scales, despite vast distances of pelagic habitat between reefs and other dispersal barriers. However, whether these dispersive widespread taxa constitute long-term panmictic populations across their species ranges remains unknown. Conventional phylogeographical inferences frequently fail to distinguish between long-term panmixia and metapopulations connected by gene flow. Moreover, marine organisms have notoriously large effective population sizes that confound population structure detection. Therefore, at what spatial scale marine populations experience independent evolutionary trajectories and ultimately species divergence is still unclear. Here, we present a phylogeographical study of a cosmopolitan Indo-Pacific coral reef fish Naso hexacanthus and its sister species Naso caesius, using two mtDNA and two nDNA markers. The purpose of this study was two-fold: first, to test for broad-scale panmixia in N. hexacanthus by fitting the data to various phylogeographical models within a Bayesian statistical framework, and second, to explore patterns of genetic divergence between the two broadly sympatric species. We report that N. hexacanthus shows little population structure across the Indo-Pacific and a range-wide, long-term panmictic population model best fit the data. Hence, this species presently comprises a single evolutionary unit across much of the tropical Indian and Pacific Oceans. Naso hexacanthus and N. caesius were not reciprocally monophyletic in the mtDNA markers but showed varying degrees of population level divergence in the two nuclear introns. Overall, patterns are consistent with secondary introgression following a period of isolation, which may be attributed to oceanographic conditions of the mid to late Pleistocene, when these two species appear to have diverged.

Historic hybridization and introgression between two iconic Australian anemonefish and contemporary patterns of population connectivity.

Endemic species on islands are considered at risk of extinction for several reasons, including limited dispersal abilities, small population sizes, and low genetic diversity. We used mitochondrial DNA (D-Loop) and 17 microsatellite loci to explore the evolutionary relationship between an endemic anemonefish, Amphiprion mccullochi (restricted to isolated locations in subtropical eastern Australia) and its more widespread sister species, A. akindynos. A mitochondrial DNA (mtDNA) phylogram showed reciprocal monophyly was lacking for the two species, with two supported groups, each containing representatives of both species, but no shared haplotypes and up to 12 species, but not location-specific management units (MUs). Population genetic analyses suggested evolutionary connectivity among samples of each species (mtDNA), while ecological connectivity was only evident among populations of the endemic, A. mccullochi. This suggests higher dispersal between endemic anemonefish populations at both evolutionary and ecological timeframes, despite separation by hundreds of kilometers. The complex mtDNA structure results from historical hybridization and introgression in the evolutionary past of these species, validated by msat analyses (NEWHYBRIDS, STRUCTURE, and DAPC). Both species had high genetic diversities (mtDNA h > 0.90, π = 4.0%; msat genetic diversity, gd > 0.670). While high gd and connectivity reduce extinction risk, identifying and protecting populations implicated in generating reticulate structure among these species should be a conservation priority.

Early mitral valve repair versus watchful waiting in patients with severe asymptomatic organic mitral regurgitation; rationale and design of the Dutch AMR trial, a multicenter, randomised trial.

BACKGROUND: Asymptomatic severe mitral valve (MV) regurgitation with preserved left ventricular function is a challenging clinical entity as data on the recommended treatment strategy for these patients are scarce and conflicting. For asymptomatic patients, no randomised trial has been performed for objectivising the best treatment strategy. METHODS: The Dutch AMR (Asymptomatic Mitral Regurgitation) trial is a multicenter, prospective, randomised trial comparing early MV repair versus watchful waiting in asymptomatic patients with severe organic MV regurgitation. A total of 250 asymptomatic patients (18-70 years) with preserved left ventricular function will be included. Intervention will be either watchful waiting or MV surgery. Follow-up will be 5 years. Primary outcome measures are all-cause mortality and a composite endpoint of cardiovascular mortality, congestive heart failure, and hospitalisation for non-fatal cardiovascular and cerebrovascular events. Secondary outcome measures are total costs, cost-effectiveness, quality of life, echocardiographic and cardiac magnetic resonance parameters, exercise tests, asymptomatic atrial fibrillation and brain natriuretic peptide levels. Additionally, the complication rate in the surgery group and rate of surgery in the watchful waiting group will be determined. IMPLICATIONS: The Dutch AMR trial will be the first multicenter randomised trial on this topic. We anticipate that the results of this study are highly needed to elucidate the best treatment strategy and that this may prove to be an international landmark study.

The pathophysiological basis of pharmacological interventions in CAVD.

Calcific aortic valve disease (CAVD) results in aortic valve stenosis and is one of the most common cardiac diseases in both Western and developing countries. The burden of this disease is expected to increase rapidly in the future, but there are still no relevant pharmacological therapies available and aortic valve replacement remains the sole definite therapy. This review presents an overview of the most common causes of CAVD, followed by current debates and trials related to the onset and progression of this disease. Several differences and similarities between the different causes of CAVD are presented. Additionally, stages of CAVD are compared with stages in atherosclerosis. Finally, future directions for research on CAVD will be discussed.

Bicuspid stenotic aortic valves: clinical characteristics and morphological assessment using MRI and echocardiography.

BACKGROUND: Bicuspid aortic valve (BAV) is one of the most common congenital heart defects with a population prevalence of 0.5% to 1.3%. Identifying patients with BAV is clinically relevant because BAV is associated with aortic stenosis, endocarditis and ascending aorta pathology. METHODS AND RESULTS: Patients with severe aortic stenosis necessitating aortic valve replacement surgery were included in this study. All dissected aortic valves were stored in the biobank of the University Medical Centre Utrecht. Additionally to the morphological assessment of the aortic valve by the surgeon and pathologist, echocardiographic and magnetic resonance imaging (MRI) images were evaluated. A total of 80 patients were included of whom 32 (40%) were diagnosed with BAV by the surgeon (gold standard). Patients with BAV were significantly younger (55 vs 71 years) and were more frequently male. Notably, a significant difference was found between the surgeon and pathologist in determining valve morphology. MRI was performed in 33% of patients. MRI could assess valve morphology in 96% vs 73% with echocardiography. The sensitivity of MRI for BAV in a population of patients with severe aortic stenosis was higher than echocardiography (75% vs 55%), whereas specificity was better with the latter (91% vs 79%). Typically, the ascending aorta was larger in patients with BAV. CONCLUSION: Among unselected patients with severe aortic valve stenosis, a high percentage of patients with BAV were found. Imaging and assessment of the aortic valve morphology when stenotic is challenging.

Systemic embolisation as presentation and recurrence of cardiac myxoma two years after surgery.

Primary cardiac tumours are rare when compared with metastatic involvement. The majority of primary cardiac tumours are benign and in adults the majority of these masses are myxomas. The treatment is surgical removal because of the risk of embolisation and/or cardiovascular complications. We describe a female presenting with systemic embolisation and recurrence of cardiac myxoma after surgery. Recurrence of myxoma is rare after surgery in case of solitary tumours but more frequent in patients with familial myxomas in association with the Carney complex. Genetic analysis revealed a mutation in the PRKAR1A gene that has never been described before. (Neth Heart J 2010;18:499502.).

Evolutionary history of the butterflyfishes (f: Chaetodontidae) and the rise of coral feeding fishes.

Of the 5000 fish species on coral reefs, corals dominate the diet of just 41 species. Most (61%) belong to a single family, the butterflyfishes (Chaetodontidae). We examine the evolutionary origins of chaetodontid corallivory using a new molecular phylogeny incorporating all 11 genera. A 1759-bp sequence of nuclear (S7I1 and ETS2) and mitochondrial (cytochrome b) data yielded a fully resolved tree with strong support for all major nodes. A chronogram, constructed using Bayesian inference with multiple parametric priors, and recent ecological data reveal that corallivory has arisen at least five times over a period of 12 Ma, from 15.7 to 3 Ma. A move onto coral reefs in the Miocene foreshadowed rapid cladogenesis within Chaetodon and the origins of corallivory, coinciding with a global reorganization of coral reefs and the expansion of fast-growing corals. This historical association underpins the sensitivity of specific butterflyfish clades to global coral decline.

Cardiac surgery in patients irradiated for Hodgkin's lymphoma.

Background/Objectives. Therapy for Hodgkin's lymphoma is disease specific and cannot be compared with treatment for other diseases. It often includes more extensive radiotherapy on the mediastinum than for other malignancies. Cardiac morbidity is known to occur in patients previously irradiated. This study describes the postoperative course after cardiac surgery of patients previously irradiated for Hodgkin's lymphoma.Methods. From January 1990 until June 2008, 12 patients underwent cardiac surgery in the University Medical Center Utrecht after previous irradiation for Hodgkin's lymphoma. Data on radiotherapy, surgery and follow-up were collected retrospectively. The postoperative functional status was assessed by a telephone questionnaire.Results. Atrial fibrillation (33%) and pleural effusion (25%) were the most common postoperative complications. After a mean followup of 2.6+/-2.9 years four patients had died. The remaining patients were all in a favourable New York Heart Association and Canadian Cardiothoracic Society class. The estimated one-, two- and four-year survival rates were 83, 69 and 46% respectively.Conclusion. The early postoperative outcome of cardiac surgery in this population is reasonably good. The long-term results may prove to be disappointing, but the cohort is small. (Neth Heart J 2010;18:61-5.).

Infection after ICD implantation: operating room versus cardiac catheterisation laboratory.

BACKGROUND/OBJECTIVES: Since the insertion of an implantable cardioverter-defibrillator (ICD) has become technically comparable to pacemaker implantation, these procedures are increasingly being performed in a cardiac catheterisation laboratory (CCL) instead of the operating room (OR). This study aims to describe the relationship between incidence of ICD infection and procedure setting and to describe the characteristics of ICD infection. METHODS: A retrospective study was performed of first ICD implantation in 677 patients admitted to our hospital between 1996 and 2006. Implantations were performed in the OR until 2003, after 2003 they were carried out in the CCL. The follow-up was censored at one year after implantation. ICD infections were defined as pocket infection or ICD-related endocarditis and a descriptive analysis was performed. RESULTS: Cardiothoracic surgeons implanted 366 ICDs in the OR Electrophysiologists performed 301 implantations in the CCL. Pulse generators were inserted using a pectoral approach with transvenous lead systems. We identified seven ICD infections (incidence rate 1.2/100 person-years), three of which had been implanted in the OR and four in the CCL. CONCLUSION: In this single-centre study no difference in the incidence of ICD infection was observed between implantation in OR and CCL. However, a larger study will be necessary to rule out a relationship with certainty. (Neth Heart J 2009;17:95-100.).

Contrasting patterns of genetic structure in two species of the coral trout Plectropomus (Serranidae) from east and west Australia: introgressive hybridisation or ancestral polymorphisms.

Inter-specific genetic relationships among regional populations of two species of grouper (Plectropomus maculatus and Plectropomus leopardus) were examined using mitochondrial and nuclear markers. mtDNA revealed contrasting regional inter-specific patterns whilst nuclear markers revealed contrasting patterns among markers, irrespective of region. In eastern Australia (EA) the species form a single mtDNA lineage, but the two species are reciprocally monophyletic in Western Australia (WA). This supports previous evidence for hybridisation between these species on the east coast. WA P. leopardus forms a sister relationship with the EA P. leopardus-maculatus clade while WA P. maculatus is more basal and sister to the P. leopardus lineages, indicating mtDNA does not suffer from incomplete lineage sorting for these species. In contrast, one of three nuclear markers (locus 7-90TG) differentiated the species into two reciprocally monophyletic clades, with no evidence of hybridisation or ancestral polymorphism. The remaining two nuclear markers (2-22 and ETS-2) did not separate these two species, while distinguishing other plectropomid species, suggesting incomplete lineage sorting at these nuclear loci. These results together with coalescence analyses suggest that P. leopardus females have hybridised historically with P. maculatus males and that P. maculatus mitochondria were displaced through introgressive hybridisation and fixation in the P. maculatus founder population on the Great Barrier Reef. The contrasting regional patterns of mtDNA structure may be attributed to Quaternary sea-level changes and shelf width differences driving different reef configurations on each coast. These reef configurations have provided opportunities for local scale interaction and reproduction among species on the narrower EA continental shelves, but not on the broader WA continental shelves.

Contrasting genetic structures across two hybrid zones of a tropical reef fish, Acanthochromis polyacanthus (Bleeker 1855).

Hybrid zones are natural laboratories offering insights into speciation processes. Narrow hybrid zones are less common in the sea than on land consistent with higher dispersal among marine populations. Acanthochromis polyacanthus is an unusual bony marine fish with philopatric dispersal that exists as allopatric stocks of white, bicoloured and black fish on the Great Barrier Reef (GBR). At two latitudes, different morphs coexist and hybridize at narrow contact zones. Sequence data from mitochondrial Hypervariable Region 1 revealed contrasting patterns of introgression across these zones. At the northern hybrid zone, a single clade of mitochondrial haplotypes was found in all white fish, hybrids and tens of kilometres into pure bicoloured stock. At the southern hybrid zone, there was no introgression of mitochondrial genes into black fish and hybrids shared the bicoloured haplotypes. Based on this asymmetry, we postulate that black fish from the southern GBR have experienced a selective sweep of their mitochondrial genome, which has resulted in almost total reproductive isolation.

Heart transplantation in the Netherlands: quo vadis?

Heart transplantation is limited by the lack of donor organs. Twenty years after the start of the Dutch transplant programmes in Rotterdam and Utrecht the situation has even worsened, despite efforts to increase the donor pool. The Dutch situation seems to be worse than in other surrounding countries, and several factors that may influence donor organ availability and organ utilisation are discussed. The indications and contraindications for heart transplantation are presented, which are rather restrictive in order to select optimal recipients for the scarce donor hearts. Detailed data on donor hearts, rejected for transplantation, are shown to give some insight into the difficult process of dealing with marginal donor organs. It is concluded that with the current low numbers of acceptable quality donor hearts, there is no lack of capacity in the two transplanting centres nor is the waiting list limiting the number of transplants. The influence of our current legal system on organ donation, which requires (prior) permission from donor and relatives, is probably limited. The most important determinants of donor organ availability are: 1. The potential donor pool, consisting of brain dead victims of (traffic) accidents and CVAs and 2. Lack of consent to a request for donation. The potential donor pool is remarkably small in the Netherlands, due to relatively low numbers of (traffic) accidents, with an almost equal number of CVA-related brain dead patients compared with neighbouring countries. Lack of consent can only be pushed back by improved public awareness of the importance of donation and improved skills of professionals in asking permission in case there is no previous consent.

A patient with four artificial heart valves after ergotamine therapy.

A 67-year-old female was evaluated in the out-patient clinic because of shortness of breath on exertion and regular spells of fever. She had been taking ergotamine tartrate to treat migraine for more than 30 years. The patient had undergone aortic-valve replacement for aortic insufficiency three years before. On echocardiographic evaluation, severe retraction and insufficiency of the remaining native heart valves was demonstrated. Endocarditis and carcinoid syndrome were excluded. The mitral, tricuspid and pulmonary valves were all replaced by a mechanical valvular prosthesis. Pathological-anatomical evaluation of the three replaced valves and the aortic valve replaced three years earlier disclosed identical findings, compatible with long-term ergotamine use. Nine months after surgery, a sick sinus syndrome developed necessitating implantation of a DDDR pacemaker with a right atrial and a coronary sinus lead. Functional class according to the New York Heart Association improved from class III to I. After stopping the ergotamine, the fever disappeared. However, the migraine spells reoccurred which are now being treated with paracetamol.

Recommended transoesophageal echocardiographic evaluation of mitral valve regurgitation.

Valve replacement in patients with mitral valve regurgitation is indicated when symptoms occur or left ventricular function becomes impaired. Using different surgical techniques, mitral valve reconstruction has lead to earlier interventions with good clinical results. In order to determine the possibility of a mitral valve reconstruction, echocardiographic parameters are necessary. With transoesophageal echocardiography a segmental analysis of the entire mitral valve can be performed; mitral valve motion abnormalities and severity and direction of the regurgitation jet can be judged. From this analysis clues for underlying pathology can be derived as well as the eligibility of a successful mitral valve reconstruction. This article focuses on transoesophageal examination with segmental analysis in patients with mitral valve regurgitation.

Comparison of outcomes after aortic valve replacement with a mechanical valve or a bioprosthesis using microsimulation.

BACKGROUND: Mechanical valves and bioprostheses are widely used for aortic valve replacement. Though previous randomised studies indicate that there is no important difference in outcome after implantation with either type of valve, knowledge of outcomes after aortic valve replacement is incomplete. OBJECTIVE: To predict age and sex specific outcomes of patients after aortic valve replacement with bileaflet mechanical valves and stented porcine bioprostheses, and to provide evidence based support for the choice of prosthesis. METHODS: Meta-analysis of published results of primary aortic valve replacement with bileaflet mechanical prostheses (nine reports, 4274 patients, and 25,726 patient-years) and stented porcine bioprostheses (13 reports, 9007 patients, and 54,151 patient-years) was used to estimate the annual risks of postoperative valve related events and their outcomes. These estimates were entered into a microsimulation model, which was employed to calculate age and sex specific outcomes after aortic valve replacement. RESULTS: Life expectancy (LE) and event-free life expectancy (EFLE) for a 65 year old man after implantation with a mechanical valve or a bioprosthesis were 10.4 and 10.7 years and 7.7 and 8.4 years, respectively. The lifetime risk of at least one valve related event for a mechanical valve was 48%, and for a bioprosthesis, 44%. For LE and EFLE, the age crossover point between the two valve types was 59 and 60 years, respectively. CONCLUSIONS: Meta-analysis based microsimulation provides insight into the long term outcome after aortic valve replacement and suggests that the currently recommended age threshold for implanting a bioprosthesis could be lowered further.