Effect of Inotropic Stimulation on Left Atrial Appendage Function in Atrial Myopathy of Chronic Atrial Fibrillation

Abstract

Atrial fibrillation (AF) leads to remodeling of the left atrium (LA) and left atrial appendage (LAA), resulting in atrial myopathy. Reduced LA and LAA function in chronic AF leads to thrombus formation and spontaneous echo contrast (SEC). The effect of inotropic stimulation on LAA function in patients with chronic AF is unknown. LAA emptying velocity (LAAEV) and maximal LAA area at baseline and after dobutamine were measured by transesophageal echocardiography in 14 subjects in normal sinus rhythm (NSR) and 6 subjects in AF. SEC in the LA was assessed before and after dobutamine. LAAEV increased significantly in both groups. However, the LAAEV at peak dobutamine in patients with AF remained significantly lower than the baseline LAAEV in patients who were in NSR (P = 0.009). Maximal LAA area decreased significantly with dobutamine in both groups, but LAA area at peak dose of dobutamine in patients with AF remained greater than baseline area in those in NSR (P = 0.01). Despite the increase in LAAEV, SEC improved in only two of five patients. We conclude that during AF, the LAA responds to inotropic stimulation with only a modest improvement in function.

Reversal of Atrial Mechanical Stunning After Cardioversion of Atrial Arrhythmias

“…A small clinical study of the effect of dobutamine in patients with chronic AF reported a modest improvement in left atrial appendage function and a decrease in LASEC in 2 of 5 patients. 19 In the present study, isoproterenol resulted in a significant increase in LAAEV, returning stunned atrial mechanical function to magnitudes in excess of pre-RFA values (62% greater) with the disappearance of LASEC. To our knowledge, the disappearance of LASEC by pharmacological maneuvers has not previously been described in the human atrium.…”

AVE0118, Blocker of the Transient Outward Current ( I to ) and Ultrarapid Delayed Rectifier Current ( I Kur ), Fully Restores Atrial Contractility After Cardioversion of Atrial Fibrillation in the Goat

“…9 The development of a therapy for AF-induced atrial contractile dysfunction with positive inotropic drugs has been hampered by the limited efficacy and low safety of these compounds. In some studies, isoprenaline 10 and dobutamine 11 showed only very limited effect on atrial contraction in patients after cardioversion of AF. In another study, dobutamine and intravenous administration of Ca 2ϩ nearly restored atrial contraction, but these drugs, given for days to weeks, may cause arrhythmias and ventricular cardiomyopathy, obviously limiting their use in the clinical setting of AF.…”

Blockade of atrial-specific K+-currents increases atrial but not ventricular contractility by enhancing reverse mode Na+/Ca2+-exchange

“…Use of positive inotropic drugs to improve atrial contractile function soon after cardioversion might reduce the risk of stroke during the post cardioversion period [5,6]. However, the limited efficacy and low safety of most of these compounds has limited the development of positive inotropic drugs to treat AF-induced atrial contractile dysfunction [7][8][9]. The ultrarapid delayed rectifier current (I Kur ) is an important determinant of repolarisation or refractoriness in the atria of dogs [10], pigs [11,12], goats [13], and humans [14].…”