Left Atrium and Cardiovascular Risk: Does Functionality Matter More Than Size?

Abstract

T he left atrium (LA) is often regarded as a biomarker of cardiovascular risk. It serves several important functions: it modulates left ventricular filling and cardiovascular performance by functioning as a reservoir for pulmonary venous return during ventricular systole; it is a conduit for pulmonary venous return during early ventricular diastole; and it functions as a booster pump that augments ventricular filling during late ventricular diastole. 1 It is highly dynamic and demonstrates structural, functional, and electrical remodeling in a time-dependent manner in response to various patho-physiological insults. The hallmark of structural remodeling is atrial dilatation and is frequently accompanied by increased interstitial fibrosis with cardiac structural alterations. 2 Functional impairment may occur with or without alteration in LA size. Remodeling that occurs in the initial phase is often reversible, 3 in contrast to remodeling that occurs with ongoing "stressors" over longer duration. 4 These maladaptive changes have a strong association with a wide array of conditions, including heart failure, 4 hypertension, 5 myocardial ischemia, 6 obesity, 7 and obstructive sleep apnea. 8 In tandem with structural change, electrophysiologic abnormalities develop, including global and regional conduction slowing and changes in refractoriness predisposing to onset of atrial arrhythmias and ultimately atrial fibrillation (AF). Atrial size and function can be assessed with echocardio-graphy, cardiac computed tomography, and cardiac magnetic resonance, but because of its safety, relative low cost, and universal availability, echocardiography is the most widely applied first-line modality. Many of the earlier measures of atrial function were only measurable during sinus rhythm, making comparisons in subjects with AF challenging. These measures include the following: (1) peak "A" wave velocity and velocity time integral of transmitral flow in late diastole; (2) estimation of the fractional contribution of atrial contraction to total mitral inflow; and (3) the use of Doppler tissue imaging as a global measure of atrial function. Recent advances in 2-and 3-dimensional echocardiography, including in tissue Doppler imaging, and speckle tracking for strain analysis 9 have allowed evaluation of atrial function during AF. These varying parameters have distinct strengths and weaknesses and are complementary in differing clinical scenarios. The LA function index (LAFI) uses volumetric measurement of the LA and is a composite rhythm-independent measure of LA function. It is a ratio that incorporates analogues of cardiac output, atrial reservoir function, and LA size and is calculated as follows: LAFI=(LA emptying fraction9velocity time integral across the left ventricular outflow tract)/largest LA volume measure in ventricular systole indexed to body surface area. 10 Thus, LAFI increases proportionally to LA reservoir function and stroke volume, but it is inversely proportional to LA size. It has become increasingly recognized that structural and functional remodeling are important factors that determine cardiovascular prognosis and risk stratification. Several studies have demonstrated this association in different population subsets. In a single-center study 11 that included ambulatory patients with heart failure and reduced ejection fraction (<40%) who were clinically stable and optimally treated, LAFI was a predictor of long-term survival. Patients in the lower LAFI quartile had more severe heart failure symptoms, renal function, and left ventricular systolic function. Subgroup analysis by heart rhythm (sinus rhythm versus AF) revealed that this remained consistent in both subgroups. LAFI was also noted to be a predictor of heart failure hospitalization in another population-based cohort study with stable coronary artery disease and preserved baseline ejection fraction (≥50%). 12 Besides functional remodeling, LA enlargement alone estimated by LA volume indexed to body