LAUSR

The rapid irregular atrial electrical activity during atrial fibrillation (AF) is associated with an irregular and variable left ventricular (LV) systolic pump function. The effects of cycle length (CL) variations on LV function during AF remain incompletely understood. To elucidate the physiological mechanisms by which beat-to-beat changes in cycle length affect LV function during AF. We hypothesize that changes in LV preload and afterload cause a large part of the beat-to-beat variability of LV function during AF. Beat-to-beat speckle-tracking echocardiography was performed in 10 patients with persistent AF. In each patient, a hundred consecutive beats were imaged during AF and we evaluated the relation between longitudinal strain in the image plane (4-chamber view) and (pre-)preceding CL in these patients. We used the CircAdapt cardiovascular system model to simulate cardiac mechanics and hemodynamics during AF for each individual patient 1) by imposing the exact irregular sequence of CLs as measured in the patient and 2) by making the atrial myocardium non-contractile. We also simulated generic (i.e. artificially defined) CL sequences (e.g. irregular long CL, irregular short CL) to better understand the determinants of beat-to-beat variations of LV systolic function during AF. Generic simulations uncovered the hemodynamic effects of a sudden irregular long or short beat on LV function during the following beat (top). A short beat led to lower LV function in the following beat because of smaller preload, while a longer beat led to larger LV function by Frank-Starling law of contractile myocardium. This CL dependency of LV function was confirmed when analysing clinical data of AF patients (bottom, left). A negative non-linear relation between preceding CL and longitudinal strain was observed (bottom, right). Increased longitudinal strain at high preceding CL (purple box) was explained by a higher preceding EDV (higher preload) (p<0.002). At a given preceding CL, variability in longitudinal strain was explained by the afterload of the preceding beat, with a lower preceding afterload (systolic aortic pressure) leading to higher longitudinal strain (yellow box, p<0.002), but not by changes in preceding preload (non-significant). Irregularity in preceding CL leads to changes in LV function through preload and afterload changes. Indeed, as observed in patients during AF, longitudinal LV strain depends non-linearly on the preceding CL. Beat-to-beat changes in preload contribute to variable LV function but changes in afterload also are a key determinant of LV function variability at same preceding CL. Our combined clinical-computational study highlights the variability in longitudinal strain measurement during AF and provides new insight into the physiological mechanisms determining LV function in AF patients. Determinants of LV function in AF Type of funding source: Public grant(s) – National budget only. Main funding source(s): NWO-ZonMw, VIDI grant 016.176.340