Echocardiographic Evaluation of Spironolactone on Myocardial Remodeling in Atrial Fibrillation with Preserved Ejection Fraction: the INSPIRE-AF randomized controlled trial

BackgroundBy means of echocardiographic assessment and deformation analysis we sought to evaluate the effect of spironolactone versus placebo in addition to standard treatment in patients with paroxysmal or persistent atrial fibrillation (AF) and preserved ejection fraction regarding the performance of the left atrium (LA) and the left ventricle (LV), and quality of life (QOL). MethodsPresent double-blind, placebo-controlled study enrolled 125 patients with a history of paroxysmal (n=58) and persistent (n=67) non-valvular AF and LVEF [≥]45% that were randomized to spironolactone 25 mg (n=63) or placebo (n=62) once daily in addition to optimal standard treatment. Comprehensive echocardiography and QOL were obtained at inclusion and after 12 months. The primary outcome was 12-month change in LA reservoir function as assessed by peak atrial longitudinal strain (PALS) and peak strain rate (SR-s). Secondary outcomes included LA phasic volumes, global longitudinal strain of left ventricle (GLS), E/e ratio, QOL, and recurrent documented episodes of AF. ResultsSpironolactone improved the LA reservoir function documented by PALS and SR-s (P =0.03 and P =0.02 for adjusted treatment effect, respectively) but only when adjusting for the parallel changes in blood pressure. Blood pressure significantly reduced in the spironolactone-treated subjects and affected primary outcomes, but not diastolic indices of LV. Transmitral E velocity and E/e ratio reduced significantly by spironolactone (P=0.009 for adjusted treatment effect). No differences in secondary outcome parameters were found across treatment groups including volumes, LA geometry, GLS, total number AF recurrences, time-to-first AF recurrence or QOL. ConclusionSpironolactone improved left atrial reservoir function by lowering blood pressure and decrease E/e ratio but did not affect left atrial volumes or geometry, quality of life or recurrent episodes of atrial fibrillation. Trial registration: ClinicalTrials.org identifier NCT02764619 and EudraCT identifier 2013-000797-30.