Mechanical aortic valve replacement in non-elderly adults: meta-analysis and microsimulation.

AIMS: To support decision-making regarding prosthetic valve selection in non-elderly adults, we aim to provide a detailed overview of outcome after contemporary mechanical aortic valve replacement (AVR). METHODS AND RESULTS: A systematic review was conducted for papers reporting clinical outcome after AVR with bileaflet mechanical valves with a mean patient age ≥18 and ≤55 years, published between 1 January 1995 and 31 December 2015. Through meta-analysis outcomes were pooled and entered into a microsimulation model to calculate (event-free) life expectancy and lifetime event risk. Twenty-nine publications, encompassing a total of 5728 patients with 32 515 patient-years of follow-up (pooled mean follow-up: 5.7 years), were included. Pooled mean age at surgery was 48.0 years. Pooled early mortality risk was 3.15% (95% confidence interval (CI):2.37-4.23), late mortality rate was 1.55%/year (95%CI:1.25-1.92); 38.7% of late deaths were valve-related. Pooled thromboembolism rate was 0.90%/year (95%CI:0.68-1.21), major bleeding 0.85%/year (95%CI:0.65-1.12), nonstructural valve dysfunction 0.39%/year (95%CI:0.21-0.76), endocarditis 0.41%/year (95%CI:0.29-0.57), valve thrombosis 0.14%/year (95%CI:0.08-0.25), structural valve deterioration 0.00%/year (zero events observed), and reintervention 0.51%/year (95%CI:0.37-0.71), mostly due to nonstructural valve dysfunction and endocarditis. For a 45-year-old, for example, this translated to an estimated life expectancy of 19 years (general population: 34 years) and lifetime risks of thromboembolism, bleeding and reintervention of 18%, 15%, and 10%, respectively. CONCLUSION: This study demonstrates that outcome after mechanical AVR in non-elderly adults is characterized by suboptimal survival and considerable lifetime risk of anticoagulation-related complications, but also reoperation. Non-elderly adult patients who are facing prosthetic valve selection are entitled to conveyance of evidence-based estimates of the risks and benefits of both mechanical and biological valve options in a shared decision-making process.

Association of two single nucleotide polymorphisms from genomewide association studies with clinical phenotypes of cerebral ischemia.

BACKGROUND: Recent genomewide association studies have revealed an association between two single nucleotide polymorphisms, rs11833579 and rs12425791, and ischemic stroke. AIM: To gain more insight in pathophysiological mechanisms underlying the found associations by exploring relationships between these single nucleotide polymorphisms and clinical and radiological characteristics of patients with cerebral ischemia. METHODS: Our cohort consisted of 660 Caucasian patients with cerebral ischemia; from all patients detailed clinical and radiological data were available. Etiologic subtype of cerebral ischemia was determined according to the TOAST classification and an alternative classification. We studied associations between risk alleles and etiologic subtype, duration of ischemia, occurrence of multiple events, functional outcome and findings on CT-angiography by means of logistic regression analysis. RESULTS: The risk allele of rs11833579 was associated with an atherothrombotic etiology of cerebral ischemia, but not with other etiologic subtypes. Risk alleles of both single nucleotide polymorphisms were related to events of shorter duration (<24 h), the risk allele of rs11833579 with occurrence of multiple events. There was no association between single nucleotide polymorphism and clinical outcome. Both single nucleotide polymorphismswere associated with presence of stenotic calcifications and stenosis >30% in a symptomatic artery on CT-angiography. CONCLUSIONS: This is the first study to show an association of rs11833579 with multiple episodes of cerebral ischemia of atherothrombotic origin, and of rs11833579 and rs12425791 with short duration of ischemia. Also, we found an association of both single nucleotide polymorphisms with atherosclerotic lesions in the extracranial vessels on CT-angiography. Together this suggests a relationship between the two single nucleotide polymorphisms and large artery pathology.