Type B aortic dissection triggered by heart transplantation in a patient with Marfan syndrome

Heart transplantation in patients with Marfan syndrome is challenging and raises concerns with regards to the haemodynamic and immunosuppressive-induced effects on the inherently fragile aorta. Most aortic events following transplantation reported so far in the literature occurred in patients with pre-existent distal aortic dissection. We report a case of successful orthotopic heart transplantation in a patient with Marfan syndrome that was complicated by late-onset type B dissection in pre-existing mild and stable distal aortic dilation. Serial aortic imaging revealed progressive growth at the level of the descending thoracic aorta. An open thoracoabdominal aortic repair procedure was successfully performed 6 months after the transplantation

Clinical characteristics and short-term outcome of patients admitted with heart failure in Belgium : results from the BIO-HF registry

Aims: Hospitalization for acute decompensated heart failure (HF) is associated with poor outcome. As specific data for Belgium are currently not available, the aim of the Belgian BIO-HF registry is to evaluate the clinical characteristics, in-hospital mortality and outcomes after discharge of patients hospitalized for acute HF. Methods and results: This is a prospective observational cohort study conducted in 2 Belgian hospitals. For the current analysis, the first 904 patients who were enrolled between 2008 and 2012 were selected for assessment of clinical characteristics and short-term outcome (all-cause mortality and all-cause mortality + rehospitalization 3 months after discharge). Mean age of patients was 77 years (51% >= 80 years), 44% were women and 64% had an eGFR = 50%. In-hospital mortality was 7.1% with a mortality of 22% in the subgroup of patients with a creatinine >= 2 mg/dl and systolic blood pressure <= 110 mmHg on admission. Three months after discharge, the all-cause mortality rate was 7.6% and the all-cause mortality or hospitalization for HF 18.3%. Multivariate Cox regression analysis revealed eGFR, COPD, absence of beta blockers and atrial fibrillation at discharge (all P < 0.05)as independent predictors of all-cause mortality. Conclusions: In this Belgian registry of mainly elderly patients admitted with acute HF, a relatively preserved EF and a reduced kidney function were present in the majority of patients. In-hospital and short-term mortality after discharge remain high and are mainly related to the presence of co-morbidities such as renal failure and COPD. Co-morbidities should be the focus for future efforts to improve the dire outcome of these patients

Tailoring the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines for the interpretation of sequenced variants in the FBN1 gene for Marfan syndrome : proposal for a disease- and gene-specific guideline

Background: The introduction of next-generation sequencing techniques has substantially increased the identification of new genetic variants and hence the necessity of accurate variant interpretation. In 2015, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology proposed new variant interpretation guidelines. Gene-specific characteristics were, however, not considered, sometimes leading to inconsistent variant interpretation. Methods: To allow a more uniform interpretation of variants in the FBN1 (fibrillin-1) gene, causing Marfan syndrome, we tailored these guidelines to this gene and disease. We adapted 15 of the 28 general criteria and classified 713 FBN1 variants previously identified in our laboratory as causal mutation or variant of uncertain significance according to these adapted guidelines. We then compared the agreement between previous methods and the adapted American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Results: Agreement between the methods was 86.4% (K-alpha, 0.6). Application of the tailored guidelines resulted in an increased number of variants of uncertain significance (14.5% to 24.2%). Of the 85 variants that were downscaled to likely benign or variant of uncertain significance, 59.7% were missense variants outside a well-established functional site. Available clinical- or segregation data, necessary to further classify these types of variants, were in many cases insufficient to aid the classification. Conclusions: Our study shows that classification of variants remains challenging and may change over time. Currently, a higher level of evidence is necessary to classify a variant as pathogenic. Gene-specific guidelines may be useful to allow a more precise and uniform interpretation of the variants to accurately support clinical decision-making