The 2019 ESC Guidelines on the Diagnosis and Management of Acute Pulmonary Embolism

has spent many years working on the genetic causes of HCM and DCM and understanding the mechanism by which these mutations alter their physiology.With HCM, a key breakthrough was the discovery of a specific change in the dynamics of contraction and relaxation.Meanwhile, her work with DCM centred on the most common cause-mutations in the gene which makes the protein sarcomere titin, the biggest protein in the human genome.Parallel molecular strategies have also led to understanding of the genetic basis for congenital heart disease.'These malformations occur in 0.7% of all live births, which is a huge burden of disease, and in about one-tenth of newborns, the baby has a severe malformation.Modern interventions can correct many of the severe heart defects, but patients still have risks for arrhythmias and progression to heart failure', explained Prof. Seidman.She emphasized that understanding of the genetic causes for adult-onset heart disease can accelerate understandings of some of the processes that occur in malformed hearts and help to tackle congenital heart disease.Prof. Seidman, who founded the Cardiovascular Genetics Center in 1992 and is author of over 400 peer-reviewed articles, believes genomic sequencing will be at the heart of future research and cardiovascular science and will help 'improve early diagnosis, appropriate interventions, and long-term outcomes.When we started, we could work on one gene at a time, now we can scale a cadre of genes involved in diseases or all genes coded in the genome', she said, adding that a better understanding of the exome could help deliver advances in knowledge of the genetic architecture of heart disease and offer information on how regulation and expression occur.'That will allow therapies to target the molecules and pathways that are altered by human mutations and hopefully will improve approaches to treat patients with heart muscle disease', she continued.Future work involves expanding the discovery of other mutations that cause heart disease by genome sequencing and transcriptional analyses, so as to further understand the mechanism of hypertrophic and dilated cardiomyopathies and congenital heart disease.(1) Revised risk-adjusted management algorithm for acute pulmonary embolism (PE; Central Illustration) (2) D-dimer cut-off values adjusted for age or clinical probability in PE diagnosis