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Our group has recently shown that in some patients, heart failure with preserved ejection fraction (HFPEF) may be explained by ‘atrial dyssynchrony syndrome’ (ADS) due to interatrial conduction delay (IACD), a short left atrioventricular interval (LAVI), and increased left atrial (LA) stiffness. Our primary objective was to evaluate LA pacing therapy as a new treatment to restore left ventricular active filling in patients with no other known causes for HF than ADS.Six patients with severe HFPEF with IACD (P wave duration >120 ms in lead II), short LAVI during electrophysiological studies (<70 ms), a restrictive filling pattern (E/e' >15), and no standard indication for a pacemaker were implanted with a lead screwed inside the coronary sinus for active LA pacing. After 3 months of active pacing, a 2 week randomized double-blind crossover phase compared active vs. inactive LA pacing. After 3 months of pacing, the mean distance walked in 6 min (6MWD) was 21% greater (240 ± 25 m vs. 190 ± 15m, P < 0.05), mitral A wave duration was longer (104 ± 8 vs. 158 ± 25 ms, P = 0.002), and E/A and E/e' ratios were smaller (3.4 ± 1.3 vs. 1.8 ± 0.9, P = 0.009, and 22.6 ± 4.6 vs. 15.3 ± 4.3, P = 0.006, respectively). Inactivation of pacing for 1 week led to a significant reduction in the 6MWD, with an on/off response.The beneficial effects of LA pacing observed in this pilot study will have to be confirmed by the randomized, controlled crossover ‘LEAD’ study.