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In the last twelve years the clinical management of patients with atrial fibrillation has been revolutionised by the introduction of direct oral anticoagulants. Despite the large amount of evidence produced, some populations remain relatively poorly explored regarding the effectiveness and safety of direct oral anticoagulants, such as the oldest and/or frailest individuals. Frailty is clinical syndrome characterized by a reduction of functions and physiological reserves which results in individuals having higher vulnerability. While current evidence underlines a relationship between atrial fibrillation and frailty, particularly in determining a higher risk of adverse outcomes, data regarding effectiveness and safety of direct oral anticoagulants in frailty atrial fibrillation patients are still lacking, leaving uncertainty about how to guide prescription in this specific subgroup. On these premises, this multidisciplinary consensus document explains why it would be useful to integrate the clinical evaluation performed through comprehensive geriatric assessment to gather further elements to guide prescription of direct oral anticoagulants in such a high-risk group of patients.

Background and Purpose: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease, Methods: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis., Results: In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease., Conclusions: In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series., (© 2016 American Heart Association, Inc.)