Atrial fibrillation in heart failure: drugs or ablation?

Atrial fibrillation (AF) and heart failure (HF) frequently coexist and mutually exert negative influences with important clinical implications. Although there is evidence that restoring and maintaining sinus rhythm may have favourable clinical effects in patients with HF, there is no evidence of a survival benefit with pharmacological antiarrhythmic intervention compared with a heart rate control strategy. In these patients, transcatheter ablation (CA) of AF represents a procedure with an excellent safety profile in centres with expertise and a high volume of interventions. However, in the absence of definite evidence of benefit on major clinical end-points that can be generalized to the heterogeneous population with AF and HF, the option of CA should be discussed and shared with the patient, and mainly considered in patients with conditions that are associated with a greater prospect of clinical benefit, such as 'young' age (65-70 years), good health conditions and few or no comorbidities, recent onset of HF and AF (especially if with high heart rate), left atrial volume not excessively compromised (<55 mm in diameter), and without evidence of substantial fibrotic remodelling, left ventricular ejection fraction (LVEF) >25%, including HF with preserved EF (HFpEF).

Migraine pathways and the identification of novel therapeutic targets.

Introduction: Migraine is a chronic neurovascular disorder characterized by recurrent headache attacks associated with neurological and autonomic symptoms. The pathophysiological mechanisms of the disease are extremely complex, involving hypothalamic and trigeminovascular activation, cortical spreading depression, release of pro-inflammatory peptides, peripheral and central sensitization. The underlying cellular and molecular mechanisms have been scarcely investigated. Recently, genetic studies have suggested that different metabolic pathways could be involved in the pathogenesis of migraine.Areas covered: This review focuses on cellular and molecular mechanisms involved in migraine, suggesting a role for circadian clocks, ion channels, synaptic plasticity, vascular factors, ion metal homeostasis, and impaired glucose metabolism in the pathogenesis of the disease. Accordingly, the article proposes new therapeutic targets that may be of particular relevance for disease prevention.Expert opinion: Several complex molecular mechanisms are involved in setting the genetic threshold for migraine and the pathogenesis of headache attacks. Most promising new therapeutic targets are the modulation of hypothalamic activity and ion channels involved in pain transmission. Further studies in animals and humans are necessary to enhance the elucidation of the molecular mechanisms of migraine and open new avenues for disease prevention.