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Development of effective atrial fibrillation (AF) prevention strategies has become a research priority to reduce the global burden of this arrhythmia. With an estimated prevalence in 2010 of 8.8 million adults aged >55 years and a projected prevalence of 17.9 million by 2060 in the European Union,1 AF is the most frequent cardiac arrhythmia and is associated with increased morbidity and mortality. Data from several North American and Western European registries provide important information to better understand the epidemiology of AF and form the basis for the development of effective AF preventive interventions. Creation of models that predict the occurrence of AF is one of the first steps to identify the demographic characteristics and cardiovascular risk factors that can be modified or treated to reduce the burden of AF. Furthermore, the assessment of the structural substrate associated with an increased risk of AF (inflammation, fibrosis, structural and electrical remodelling of the left atrium) is also important. The addition of echocardiographic parameters (left atrial (LA) diameter, the sum of diastolic interventricular septal and posterior wall thickness and LV fractional shortening) to the model derived from the Framingham Heart Study slightly improved the discrimination of the model, particularly in individuals with valvular heart disease or heart failure.2
The number of studies evaluating the association between several echocardiographic variables and the risk of AF across different subpopulations is growing and LA size and LV systolic and diastolic dysfunctions are the main focus of those studies. In their Heart paper, Tiwari et al3 provide further evidence by demonstrating that the addition of LA size and LV diastolic function to a number of sociodemographic variables and cardiovascular risk factors increased the ability of the model to predict the occurrence of AF in 2406 participants of the Tromsø study. During the 16-year follow-up, 462 (19%) individuals presented with AF (incidence: 12.6/1000 person years). Severely enlarged left atrium (>2.8 cm/m2) was independently associated with the occurrence of AF (HR 4.2; 95% CI 2.7 to 6.5, p<0.001), whereas the presence of LV diastolic dysfunction (defined as abnormal transmitral Doppler flow) was not associated. However, the presence of LV diastolic dysfunction modified the association between LA size and AF by increasing the risk of AF by 30%. These results are consistent with previous series evaluating the incremental value of LV diastolic dysfunction to LA size to predict AF across different populations.4 ,5
Increased LV filling pressures and stiffness and decreased compliance characterise LV diastolic dysfunction which leads to increased atrial wall tension, LA enlargement and wall fibrosis. This LA structural remodelling forms the substrate for initiating and perpetuating AF. The increased fibrosis leads to shortening of atrial refractoriness, areas of slow conduction and increased non-uniform anisotropy that lead to re-entrant circuits. Therefore, it could be hypothesised that the simple measurement of LA size and assessment of LV diastolic function could identify those patients at increased risk of developing AF. As Tiwari et al conclude, LA size (and structural changes) may be a marker of the chronicity of exposure to increased LV filling pressures and the strongest predictor of incident AF. However, this association is not as simple as it appears. LA dilatation is not always pathological and it does not occur only in response to increased LV filling pressures. Indeed, among the participants of this registry, there were a significant proportion of patients with moderately or severely enlarged left atrium and normal LV diastolic filling who presented with AF at follow-up. An example of LA remodelling different from the pathological structural remodelling observed in individuals with LV diastolic dysfunction is that observed in elite athletes, a subpopulation in which the risk of atrial arrhythmias remains controversial. In endurance athletes, LA dilatation reflects a physiological adaptation to increased LV volumes and cardiac output and is characterised by an increase in LA reservoir function and compliance (or decreased stiffness).6 Experimental models have shown that continuous intense endurance programme induced reversible fibrotic changes of the LA wall.7 However, these results have not been reproduced in humans and, therefore, an imbalance between sympathetic and parasympathetic nervous systems with an increase in vagal tone, shortening of the effective refractory period and increased non-uniform anisotropy remains as an important mechanism explaining the increased risk of AF in this group.
Advances in non-invasive imaging techniques have permitted characterisation of the arrhythmogenic substrate and may help to differentiate the pathological LA remodelling from the physiological remodelling.8 Echocardiographic tissue Doppler imaging and speckle tracking permit the assessment of total atrial activation time and active deformation of the atrial myocardium and the reservoir function, respectively. A prolonged total atrial activation time and a decreased reservoir function have been associated with increased risk of AF and these parameters have been considered indirect surrogates of fibrotic remodelling of the LA wall.8 Late gadolinium contrast-enhanced magnetic resonance technique permit direct quantification of diffuse and focal fibrosis of the atrial wall.8 The presence of extensive late gadolinium enhancement has been associated with permanent forms of AF and low success rate of radiofrequency catheter ablation techniques. Whether the use of these imaging techniques (beyond the simple measurement of the LA diameter) may help to refine the risk stratification of individuals who are at risk of developing AF and to develop effective interventions that reduce the global burden of AF needs to be demonstrated.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.
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