Risk Stratification for Stroke in Atrial Fibrillation: A Critique

Ammar M. Killu; Christopher B. Granger; Bernard J. Gersh


Eur Heart J. 2019;40(16):1294-1302. 

In This Article

Pathophysiology of Atrial Fibrillation

Although the pathophysiology of AF is incompletely understood, it is useful to view it as a spectrum (Figure 1). On one end are patients with 'lone' AF. These are younger patients without significant cardiovascular risk factors or structural heart disease; in some, heightened vagal tone or a genetic substrate plays a role. The arrhythmia is caused by triggers, most commonly arising from the pulmonary veins. As such, the majority of such patients have a paroxysmal pattern. At the other end of the spectrum are patients with triggers compounded by an underlying degenerative substrate. In the presence of an appropriate substrate, a focal trigger can result in high-frequency local re-entry, called a 'rotor'. Fibrillatory waves can disseminate from rotors giving rise to, and sustaining, AF.[6] In addition to increasing age, other cardiovascular risk factors such as obesity, metabolic syndrome, atherosclerosis, and hypertension play prominent roles. These patients tend to have more persistent/permanent forms of AF despite management of potential triggers. The mechanism by which such comorbidities lead to AF includes increased arterial stiffness and consequent diastolic dysfunction. This results in a dilated left atrium that is increasingly prone to fibrillation. In addition, systemic inflammation may also contribute to, and perpetuate, AF given the association with C-reactive protein (CRP), interleukins, and tumour necrosis factor-α, to name a few (see below).[7] The genetic contribution to AF is not fully defined. Established AF susceptibility loci account for only 22%.[8] Even less clear is the contribution of genetic susceptibility to stroke in AF. Remarkably, however, two studies have linked the gene variant of 4q25 (known to associate with AF) to cardioembolic types of stroke.[9,10] As such, some of the susceptibility to stroke in AF appears to be genetically determined.

Figure 1.

Schematic representation highlighting the main differences between atrial fibrillation subtypes. Lone atrial fibrillation tends to be paroxysmal and associated with triggers. More persistent or permanent forms of atrial fibrillation tend to be associated with triggers as well as an underlying substrate. Cardiovascular parameters are more prevalent in this population. Courtesy of Dr Douglas Packer, Mayo Clinic, Rochester, MN, USA.